{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:08:39Z","timestamp":1781082519739,"version":"3.54.1"},"reference-count":130,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017481","name":"Ulusal Metroloji Enstit\u00fcs\u00fc, T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ftirma Kurumu","doi-asserted-by":"publisher","award":["118C346"],"award-info":[{"award-number":["118C346"]}],"id":[{"id":"10.13039\/501100017481","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nanomaterials"],"abstract":"<jats:p>Cancer stem cells (CSCs) are a subpopulation of cells that can initiate, self-renew, and sustain tumor growth. CSCs are responsible for tumor metastasis, recurrence, and drug resistance in cancer therapy. CSCs reside within a niche maintained by multiple unique factors in the microenvironment. These factors include hypoxia, excessive levels of angiogenesis, a change of mitochondrial activity from aerobic aspiration to aerobic glycolysis, an upregulated expression of CSC biomarkers and stem cell signaling, and an elevated synthesis of the cytochromes P450 family of enzymes responsible for drug clearance. Antibodies and ligands targeting the unique factors that maintain the niche are utilized for the delivery of anticancer therapeutics to CSCs. In this regard, nanomaterials, specifically nanoparticles (NPs), are extremely useful as carriers for the delivery of anticancer agents to CSCs. This review covers the biology of CSCs and advances in the design and synthesis of NPs as a carrier in targeting cancer drugs to the CSC subpopulation of cancer cells. This review includes the development of synthetic and natural polymeric NPs, lipid NPs, inorganic NPs, self-assembling protein NPs, antibody-drug conjugates, and extracellular nanovesicles for CSC targeting.<\/jats:p>","DOI":"10.3390\/nano11071755","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T22:02:04Z","timestamp":1625522524000},"page":"1755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":85,"title":["Nanoparticles for Targeted Drug Delivery to Cancer Stem Cells: A Review of Recent Advances"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6791-7484","authenticated-orcid":false,"given":"Yavuz Nuri","family":"Ertas","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Erciyes University, Kayseri 38039, Turkey"},{"name":"ERNAM\u2014Nanotechnology Research and Application Center, Erciyes University, Kayseri 38039, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1710-1759","authenticated-orcid":false,"given":"Keyvan","family":"Abedi Dorcheh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran 14115, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6027-292X","authenticated-orcid":false,"given":"Ali","family":"Akbari","sequence":"additional","affiliation":[{"name":"Solid Tumor Research Center, Research Institute for Cellular and Molecular Medicine, Urmia University of Medical Sciences, Urmia 57147, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6548-5422","authenticated-orcid":false,"given":"Esmaiel","family":"Jabbari","sequence":"additional","affiliation":[{"name":"Biomaterials and Tissue Engineering Laboratory, Department of Chemical Engineering, University of South Carolina, Columbia, SC 29208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.apsb.2020.09.016","article-title":"Recent advances in drug delivery systems for targeting cancer stem cells","volume":"11","author":"Duan","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_2","unstructured":"World Health Organization (2020). WHO Report on Cancer: Setting Priorities, Investing Wisely and Providing Care for All, WHO."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"227","DOI":"10.15283\/ijsc19006","article-title":"Application of Nanotechnology in Targeting of Cancer Stem Cells: A Review","volume":"12","author":"Asghari","year":"2019","journal-title":"Int. J. Stem Cells"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3983","DOI":"10.1073\/pnas.0530291100","article-title":"Prospective identification of tumorigenic breast cancer cells","volume":"100","author":"Wicha","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nature05372","article-title":"A human colon cancer cell capable of initiating tumour growth in immunodeficient mice","volume":"445","author":"Pollett","year":"2007","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.cell.2005.03.032","article-title":"Identification of bronchioalveolar stem cells in normal lung and lung cancer","volume":"121","author":"Kim","year":"2005","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1016\/j.ejca.2006.01.037","article-title":"Prostate cancer stem cells","volume":"42","author":"Collins","year":"2006","journal-title":"Eur. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1002\/hep.22082","article-title":"Identification of local and circulating cancer stem cells in human liver cancer","volume":"47","author":"Yang","year":"2008","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9328","DOI":"10.1158\/0008-5472.CAN-05-1343","article-title":"A tumorigenic subpopulation with stem cell properties in melanomas","volume":"65","author":"Fang","year":"2005","journal-title":"Cancer Res."},{"key":"ref_10","first-page":"5821","article-title":"Identification of a cancer stem cell in human brain tumors","volume":"63","author":"Singh","year":"2003","journal-title":"Cancer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1073\/pnas.0610117104","article-title":"Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma","volume":"104","author":"Prince","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11154","DOI":"10.1073\/pnas.0603672103","article-title":"Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness","volume":"103","author":"Szotek","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.stem.2007.06.002","article-title":"Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer","volume":"1","author":"Hermann","year":"2007","journal-title":"Cell Stem Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15178","DOI":"10.1073\/pnas.2036535100","article-title":"Cancerous stem cells can arise from pediatric brain tumors","volume":"100","author":"Hemmati","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zhao, C.-Y., Cheng, R., Yang, Z., and Tian, Z.-M. (2018). Nanotechnology for cancer therapy based on chemotherapy. Molecules, 23.","DOI":"10.3390\/molecules23040826"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1021\/acsnano.9b04266","article-title":"Integrating nanotechnology into cancer care","volume":"13","author":"Grodzinski","year":"2019","journal-title":"ACS Nano"},{"key":"ref_17","first-page":"51","article-title":"Drug-loaded polymeric nanoparticles for cancer stem cell targeting","volume":"8","author":"Li","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_18","first-page":"251","article-title":"Targeting cancer stem cells by using the nanoparticles","volume":"10","author":"Hong","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s00441-018-2928-5","article-title":"Nanomedicine in cancer stem cell therapy: From fringe to forefront","volume":"374","author":"Tabassum","year":"2018","journal-title":"Cell Tissue Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1089\/scd.2018.0118","article-title":"Novel insights into adult and cancer stem cell biology","volume":"27","author":"Bhartiya","year":"2018","journal-title":"Stem Cells Dev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3714190","DOI":"10.1155\/2017\/3714190","article-title":"Cancer stem cells and their microenvironment: Biology and therapeutic implications","volume":"2017","author":"Lau","year":"2017","journal-title":"Stem Cells Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jconrel.2017.09.028","article-title":"Nano-delivery system targeting to cancer stem cell cluster of differentiation biomarkers","volume":"266","author":"Mokhtarzadeh","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2017.00001","article-title":"Nanomaterials in targeting cancer stem cells for cancer therapy","volume":"8","author":"Qin","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1080\/21691401.2016.1236805","article-title":"Comparison study of the effect of alkyl-modified and unmodified PAMAM and PPI dendrimers on solubility and antitumor activity of crocetin","volume":"45","author":"Soltani","year":"2017","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1016\/j.drudis.2020.07.023","article-title":"Cancer stem cells and nanomedicine: New opportunities to combat multidrug resistance?","volume":"25","author":"Dalpiaz","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nunes, T., Hamdan, D., Leboeuf, C., El Bouchtaoui, M., Gapihan, G., Nguyen, T.T., Meles, S., Angeli, E., Ratajczak, P., and Lu, H. (2018). Targeting cancer stem cells to overcome chemoresistance. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19124036"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jconrel.2018.08.043","article-title":"Cancer stem cells-emanated therapy resistance: Implications for liposomal drug delivery systems","volume":"288","author":"Heidarifard","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.semcancer.2017.06.012","article-title":"Mitochondrial biology in cancer stem cells","volume":"47","author":"Loureiro","year":"2017","journal-title":"Semin. Cancer Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.jconrel.2016.11.017","article-title":"Biodegradable nano-polymers as delivery vehicles for therapeutic small non-coding ribonucleic acids","volume":"245","author":"Mokhtarzadeh","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/j.trac.2016.06.018","article-title":"Aptamers as smart ligands for nano-carriers targeting","volume":"82","author":"Mokhtarzadeh","year":"2016","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1517\/14712598.2016.1169269","article-title":"Recent advances on biocompatible and biodegradable nanoparticles as gene carriers","volume":"16","author":"Mokhtarzadeh","year":"2016","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1016\/j.addr.2013.07.012","article-title":"Role of integrated cancer nanomedicine in overcoming drug resistance","volume":"65","author":"Iyer","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1016\/j.drudis.2014.06.004","article-title":"Multidrug resistance in cancer or inefficacy of neuroactive agents: Innovative strategies to inhibit or circumvent the active efflux transporters selectively","volume":"19","author":"Pavan","year":"2014","journal-title":"Drug Discov. Today"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6762","DOI":"10.1039\/C7TB01510K","article-title":"Hybrid nanoparticles coated with hyaluronic acid lipoid for targeted co-delivery of paclitaxel and curcumin to synergistically eliminate breast cancer stem cells","volume":"5","author":"Yang","year":"2017","journal-title":"J. Mater. Chem. B"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6909","DOI":"10.2147\/IJN.S144184","article-title":"Polymer\u2013lipid hybrid anti-HER2 nanoparticles for targeted salinomycin delivery to HER2-positive breast cancer stem cells and cancer cells","volume":"12","author":"Li","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Abou-ElNaga, A., Mutawa, G., El-Sherbiny, I.M., Abd-ElGhaffar, H., Allam, A.A., Ajarem, J., and Mousa, S.A. (2017). Novel nano-therapeutic approach actively targets human ovarian cancer stem cells after xenograft into nude mice. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18040813"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1016\/j.nano.2015.07.001","article-title":"Anthothecol-encapsulated PLGA nanoparticles inhibit pancreatic cancer stem cell growth by modulating sonic hedgehog pathway","volume":"11","author":"Verma","year":"2015","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_38","first-page":"2537","article-title":"Poly (lactic-co-glycolic acid) nanoparticles conjugated with CD133 aptamers for targeted salinomycin delivery to CD133+ osteosarcoma cancer stem cells","volume":"10","author":"Ni","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.colsurfb.2016.03.075","article-title":"CD44 targeted chemotherapy for co-eradication of breast cancer stem cells and cancer cells using polymeric nanoparticles of salinomycin and paclitaxel","volume":"143","author":"Muntimadugu","year":"2016","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3343","DOI":"10.1021\/acs.molpharmaceut.8b00367","article-title":"Cargo-free nanomedicine with pH sensitivity for codelivery of DOX conjugated prodrug with SN38 to synergistically eradicate breast cancer stem cells","volume":"15","author":"Sun","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.2217\/nnm-2016-0408","article-title":"Therapeutic PEG-ceramide nanomicelles synergize with salinomycin to target both liver cancer cells and cancer stem cells","volume":"12","author":"Wang","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.biomaterials.2013.10.049","article-title":"Co-delivery of thioridazine and doxorubicin using polymeric micelles for targeting both cancer cells and cancer stem cells","volume":"35","author":"Ke","year":"2014","journal-title":"Biomaterials"},{"key":"ref_43","first-page":"6611","article-title":"The enhanced delivery of salinomycin to CD133+ ovarian cancer stem cells through CD133 antibody conjugation with poly (lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles","volume":"15","author":"Mi","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6855","DOI":"10.2147\/IJN.S181928","article-title":"Codelivery of doxorubicin and elacridar to target both liver cancer cells and stem cells by polylactide-co-glycolide\/d-alpha-tocopherol polyethylene glycol 1000 succinate nanoparticles","volume":"13","author":"Chen","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5653","DOI":"10.2147\/OTT.S141083","article-title":"The combination therapy of salinomycin and gefitinib using poly (d, l-lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles for targeting both lung cancer stem cells and cancer cells","volume":"10","author":"Zhang","year":"2017","journal-title":"OncoTargets Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6667","DOI":"10.2147\/IJN.S116230","article-title":"A novel double-targeted nondrug delivery system for targeting cancer stem cells","volume":"11","author":"Qiao","year":"2016","journal-title":"Int. J. Nanomed."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108857","DOI":"10.1016\/j.biopha.2019.108857","article-title":"The promotion of nanoparticle delivery to two populations of gastric cancer stem cells by CD133 and CD44 antibodies","volume":"115","author":"Chen","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1080\/10717544.2018.1474974","article-title":"Ratiometric delivery of two therapeutic candidates with inherently dissimilar physicochemical property through pH-sensitive core\u2013shell nanoparticles targeting the heterogeneous tumor cells of glioma","volume":"25","author":"Xu","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.biomaterials.2016.07.036","article-title":"Nanovesicle-mediated systemic delivery of microRNA-34a for CD44 overexpressing gastric cancer stem cell therapy","volume":"105","author":"Jang","year":"2016","journal-title":"Biomaterials"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biomaterials.2016.06.038","article-title":"Nanoparticle-facilitated autophagy inhibition promotes the efficacy of chemotherapeutics against breast cancer stem cells","volume":"103","author":"Sun","year":"2016","journal-title":"Biomaterials"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.biomaterials.2014.10.018","article-title":"Co-delivery of all-trans-retinoic acid and doxorubicin for cancer therapy with synergistic inhibition of cancer stem cells","volume":"37","author":"Sun","year":"2015","journal-title":"Biomaterials"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jconrel.2014.11.011","article-title":"Combination therapy with epigenetic-targeted and chemotherapeutic drugs delivered by nanoparticles to enhance the chemotherapy response and overcome resistance by breast cancer stem cells","volume":"205","author":"Li","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.2147\/IJN.S198353","article-title":"Lipid\u2013polymer hybrid nanoparticles as a next-generation drug delivery platform: State of the art, emerging technologies, and perspectives","volume":"14","author":"Mukherjee","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/aps.2017.166","article-title":"Salinomycin-loaded lipid-polymer nanoparticles with anti-CD20 aptamers selectively suppress human CD20+ melanoma stem cells","volume":"39","author":"Zeng","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1016\/j.nano.2018.05.015","article-title":"Targeted salinomycin delivery with EGFR and CD133 aptamers based dual-ligand lipid-polymer nanoparticles to both osteosarcoma cells and cancer stem cells","volume":"14","author":"Chen","year":"2018","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.1039\/C8TB02958J","article-title":"The feasibility of ROS-and GSH-responsive micelles for treating tumor-initiating and metastatic cancer stem cells","volume":"7","author":"Yu","year":"2019","journal-title":"J. Mater. Chem. B"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.nano.2016.07.017","article-title":"Combination therapy of paclitaxel and cyclopamine polymer-drug conjugates to treat advanced prostate cancer","volume":"13","author":"Yang","year":"2017","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"17793","DOI":"10.1021\/acsami.6b04403","article-title":"Targeting colorectal cancer stem-like cells with anti-CD133 antibody-conjugated SN-38 nanoparticles","volume":"8","author":"Ning","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3725","DOI":"10.1021\/acs.biomac.8b00856","article-title":"pH-and GSH-sensitive hyaluronic acid-MP conjugate micelles for intracellular delivery of doxorubicin to colon cancer cells and cancer stem cells","volume":"19","author":"Debele","year":"2018","journal-title":"Biomacromolecules"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Gaio, E., Conte, C., Esposito, D., Reddi, E., Quaglia, F., and Moret, F. (2020). CD44 Targeting Mediated by Polymeric Nanoparticles and Combination of Chlorine TPCS2a-PDT and Docetaxel-Chemotherapy for Efficient Killing of Breast Differentiated and Stem Cancer Cells In Vitro. Cancers, 12.","DOI":"10.3390\/cancers12020278"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9199","DOI":"10.2147\/IJN.S230376","article-title":"Co-Delivery of Docetaxel and Salinomycin to Target Both Breast Cancer Cells and Stem Cells by PLGA\/TPGS Nanoparticles","volume":"14","author":"Gao","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"649","DOI":"10.3389\/fchem.2020.00649","article-title":"A novel CD133-and EpCAM-targeted liposome with redox-responsive properties capable of synergistically eliminating liver cancer stem cells","volume":"8","author":"Wang","year":"2020","journal-title":"Front. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1080\/10717544.2018.1494225","article-title":"Dual-modified cationic liposomes loaded with paclitaxel and survivin siRNA for targeted imaging and therapy of cancer stem cells in brain glioma","volume":"25","author":"Sun","year":"2018","journal-title":"Drug Deliv."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"9061","DOI":"10.2147\/IJN.S262786","article-title":"89Zr-Labeled Multifunctional Liposomes Conjugate Chitosan for PET-Trackable Triple-Negative Breast Cancer Stem Cell Targeted Therapy","volume":"15","author":"Yang","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.biomaterials.2017.09.013","article-title":"pH multistage responsive micellar system with charge-switch and PEG layer detachment for co-delivery of paclitaxel and curcumin to synergistically eliminate breast cancer stem cells","volume":"147","author":"Yang","year":"2017","journal-title":"Biomaterials"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.biomaterials.2015.08.048","article-title":"Hyaluronic acid-decorated dual responsive nanoparticles of Pluronic F127, PLGA, and chitosan for targeted co-delivery of doxorubicin and irinotecan to eliminate cancer stem-like cells","volume":"72","author":"Wang","year":"2015","journal-title":"Biomaterials"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12951-018-0424-4","article-title":"Specific cancer stem cell-therapy by albumin nanoparticles functionalized with CD44-mediated targeting","volume":"16","author":"Li","year":"2018","journal-title":"J. Nanobiotechnol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.1021\/mp5003619","article-title":"Enhanced photodynamic therapy and effective elimination of cancer stem cells using surfactant\u2013polymer nanoparticles","volume":"11","author":"Usacheva","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"5725","DOI":"10.1021\/nn506928p","article-title":"Chitosan-decorated doxorubicin-encapsulated nanoparticle targets and eliminates tumor reinitiating cancer stem-like cells","volume":"9","author":"Rao","year":"2015","journal-title":"ACS Nano"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5405","DOI":"10.2147\/IJN.S166104","article-title":"Novel silk fibroin nanoparticles incorporated silk fibroin hydrogel for inhibition of cancer stem cells and tumor growth","volume":"13","author":"Wu","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2703","DOI":"10.1021\/mp5002312","article-title":"iTEP nanoparticle-delivered salinomycin displays an enhanced toxicity to cancer stem cells in orthotopic breast tumors","volume":"11","author":"Zhao","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41573-020-0090-8","article-title":"Engineering precision nanoparticles for drug delivery","volume":"20","author":"Mitchell","year":"2021","journal-title":"Nat. Rev. Drug. Discov."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1080\/1061186X.2017.1400553","article-title":"Recent advances in metal nanoparticles in cancer therapy","volume":"26","author":"Sharma","year":"2018","journal-title":"J. Drug Target."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/natrevmats.2016.73","article-title":"Evaluation of nanomedicines: Stick to the basics","volume":"1","author":"McNeil","year":"2016","journal-title":"Nat. Rev. Mater."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1039\/C9RA08192E","article-title":"Colorectal cancer stem cells: A review of targeted drug delivery by gold nanoparticles","volume":"10","author":"Mohamud","year":"2020","journal-title":"RSC Adv."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1021\/ar800035u","article-title":"Gold nanoparticles in biology: Beyond toxicity to cellular imaging","volume":"41","author":"Murphy","year":"2008","journal-title":"Acc. Chem. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.ijpharm.2016.09.076","article-title":"Gold nanoparticles enhance 5-fluorouracil anticancer efficacy against colorectal cancer cells","volume":"513","author":"Safwat","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1021\/acs.molpharmaceut.9b00132","article-title":"Salinomycin-loaded gold nanoparticles for treating cancer stem cells by ferroptosis-induced cell death","volume":"16","author":"Zhao","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_79","first-page":"2065","article-title":"Treating cancer stem cells and cancer metastasis using glucose-coated gold nanoparticles","volume":"10","author":"Hu","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jconrel.2019.01.006","article-title":"Glucose-linked sub-50-nm unimer polyion complex-assembled gold nanoparticles for targeted siRNA delivery to glucose transporter 1-overexpressing breast cancer stem-like cells","volume":"295","author":"Yi","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"8979","DOI":"10.1021\/nn502125h","article-title":"Precise Engineering of siRNA Delivery Vehicles to Tumors Using Polyion Complexes and Gold Nanoparticles","volume":"8","author":"Kim","year":"2014","journal-title":"ACS Nano"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jconrel.2016.08.041","article-title":"Targeted systemic delivery of siRNA to cervical cancer model using cyclic RGD-installed unimer polyion complex-assembled gold nanoparticles","volume":"244","author":"Yi","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1039\/B913224D","article-title":"Fabrication and functional characterization of goldnanoconjugates for potential application in ovarian cancer","volume":"20","author":"Patra","year":"2009","journal-title":"J. Mater. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"8760","DOI":"10.1073\/pnas.1002143107","article-title":"Bombesin functionalized gold nanoparticles show in vitro and in vivo cancer receptor specificity","volume":"107","author":"Chanda","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.canlet.2008.09.024","article-title":"In vitro cancer cell imaging and therapy using transferrin-conjugated gold nanoparticles","volume":"274","author":"Li","year":"2009","journal-title":"Cancer Lett."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Latorre, A., Latorre, A., Castellanos, M., Rodriguez Diaz, C., Lazaro-Carrillo, A., Aguado, T., Lecea, M., Romero-P\u00e9rez, S., Calero, M., and Sanchez-Puelles, J.M. (2019). Multifunctional albumin-stabilized gold nanoclusters for the reduction of cancer stem cells. Cancers, 11.","DOI":"10.3390\/cancers11070969"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"929","DOI":"10.2217\/nnm-2017-0320","article-title":"Magnetic iron oxide nanoparticles as drug carriers: Preparation, conjugation and delivery","volume":"13","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7549","DOI":"10.2147\/IJN.S215087","article-title":"CD44-targeted magnetic nanoparticles kill head and neck squamous cell carcinoma stem cells in an alternating magnetic field","volume":"14","author":"Su","year":"2019","journal-title":"Int. J. Nanomed."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.biomaterials.2017.10.035","article-title":"Dual-targeting Wnt and uPA receptors using peptide conjugated ultra-small nanoparticle drug carriers inhibited cancer stem-cell phenotype in chemo-resistant breast cancer","volume":"152","author":"Guo","year":"2018","journal-title":"Biomaterials"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s42247-020-00078-1","article-title":"Recent developments of mesoporous silica nanoparticles in biomedicine","volume":"3","author":"Chen","year":"2020","journal-title":"Emergent Mater."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.apsb.2018.01.007","article-title":"Mesoporous silica nanoparticles for drug and gene delivery","volume":"8","author":"Zhou","year":"2018","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1016\/j.jconrel.2020.11.015","article-title":"Novel dendritic polyglycerol-conjugated, mesoporous silica-based targeting nanocarriers for co-delivery of doxorubicin and tariquidar to overcome multidrug resistance in breast cancer stem cells","volume":"330","author":"Pan","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"19808","DOI":"10.1021\/acsami.9b04474","article-title":"Dual delivery of HNF4\u03b1 and cisplatin by mesoporous silica nanoparticles inhibits cancer pluripotency and tumorigenicity in hepatoma-derived CD133-expressing stem cells","volume":"11","author":"Tsai","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.mattod.2017.01.013","article-title":"Taking the vehicle out of drug delivery","volume":"20","author":"Shen","year":"2017","journal-title":"Mater. Today"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.actbio.2020.11.018","article-title":"Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles","volume":"119","author":"Serna","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coph.2018.12.004","article-title":"Protein-driven nanomedicines in oncotherapy","volume":"47","author":"Casanova","year":"2019","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s12195-019-00589-w","article-title":"Carrier-Free CXCR4-Targeted Nanoplexes Designed for Polarizing Macrophages to Suppress Tumor Growth","volume":"12","author":"Deci","year":"2019","journal-title":"Cell Mol. Bioeng."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s40843-019-9582-9","article-title":"Controlling self-assembling and tumor cell-targeting of protein-only nanoparticles through modular protein engineering","volume":"63","author":"Serna","year":"2020","journal-title":"Sci. China Mater."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.jmmm.2018.09.015","article-title":"Self-assembling nanoparticles biofunctionalized with magnetite-binding protein for the targeted delivery to HER2\/neu overexpressing cancer cells","volume":"469","author":"Shipunova","year":"2019","journal-title":"J. Magn. Mater."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.jiec.2020.06.012","article-title":"A self-assembly and stimuli-responsive fusion gelonin delivery system for tumor treatment","volume":"89","author":"Liu","year":"2020","journal-title":"J. Ind. Eng. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.tibtech.2017.11.007","article-title":"Protein-Based Therapeutic Killing for Cancer Therapies","volume":"36","author":"Serna","year":"2018","journal-title":"Trends Biotechnol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.semcancer.2019.11.012","article-title":"Emergence in protein derived nanomedicine as anticancer therapeutics: More than a tour de force","volume":"69","author":"Wang","year":"2021","journal-title":"Semin. Cancer Biol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"785","DOI":"10.3923\/ijp.2017.785.807","article-title":"Advantages of Drug Selective Distribution in Cancer Treatment: Brentuximab Vedotin","volume":"13","year":"2017","journal-title":"Int J. Pharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1001\/jamaoncol.2019.3552","article-title":"Antibody Drug Conjugates for Cancer Treatment","volume":"5","author":"Walko","year":"2019","journal-title":"Jama Oncol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.jconrel.2015.05.003","article-title":"New trends in guided nanotherapies for digestive cancers: A systematic review","volume":"209","author":"Fernandes","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Hafeez, U., Parakh, S., Gan, H.K., and Scott, A.M. (2020). Antibody-Drug Conjugates for Cancer Therapy. Molecules, 25.","DOI":"10.3390\/molecules25204764"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"3796","DOI":"10.1002\/anie.201307628","article-title":"Antibody-Drug Conjugates: An Emerging Concept in Cancer Therapy","volume":"53","author":"Chari","year":"2014","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1021\/bc5004982","article-title":"Site-Specific Antibody-Drug Conjugates: The Nexus of Biciorthogonal Chemistry, Protein Engineering, and Drug Development","volume":"26","author":"Agarwal","year":"2015","journal-title":"Bioconjugate Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s11095-021-02986-1","article-title":"Targeted Delivery of Combination Therapeutics Using Monoclonal Antibody 2C5-Modified Immunoliposomes for Cancer Therapy","volume":"38","author":"Narayanaswamy","year":"2021","journal-title":"Pharm Res. Dordr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-020-01546-6","article-title":"Genetic and pharmacological targeting of A2a receptor improves function of anti-mesothelin CAR T cells","volume":"39","author":"Masoumi","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1158\/1535-7163.MCT-13-0926","article-title":"Anetumab Ravtansine: A Novel Mesothelin-Targeting Antibody-Drug Conjugate Cures Tumors with Heterogeneous Target Expression Favored by Bystander Effect","volume":"13","author":"Golfier","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"5097","DOI":"10.1158\/1078-0432.CCR-15-2822","article-title":"DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1","volume":"22","author":"Ogitani","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1002\/1878-0261.12734","article-title":"The MSP-RON axis stimulates cancer cell growth in models of triple negative breast cancer","volume":"14","author":"Millar","year":"2020","journal-title":"Mol. Oncol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1186\/s40425-019-0732-8","article-title":"Therapeutic efficacy of a novel humanized antibody-drug conjugate recognizing plexin-semaphorin-integrin domain in the RON receptor for targeted cancer therapy","volume":"7","author":"Tong","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1038\/s41375-020-0755-7","article-title":"The CD33 splice isoform lacking exon 2 as therapeutic target in human acute myeloid leukemia","volume":"34","author":"Godwin","year":"2020","journal-title":"Leukemia"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1158\/1535-7163.MCT-17-1077","article-title":"IMGN779, a Novel CD33-Targeting Antibody-Drug Conjugate with DNA-Alkylating Activity, Exhibits Potent Antitumor Activity in Models of AML","volume":"17","author":"Kovtun","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Gupta, R., Leon, F., Rauth, S., Batra, S.K., and Ponnusamy, M.P. (2020). A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis. Cells, 9.","DOI":"10.3390\/cells9020446"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"23289","DOI":"10.18632\/oncotarget.25289","article-title":"Treatment of ovarian cancer by targeting the tumor stem cell-associated carbohydrate antigen, Sialyl-Thomsen-nouveau","volume":"9","author":"Starbuck","year":"2018","journal-title":"Oncotarget"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Hernandez-Oller, L., Seras-Franzoso, J., Andrade, F., Rafael, D., Abasolo, I., Gener, P., and Schwartz, S. (2020). Extracellular Vesicles as Drug Delivery Systems in Cancer. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12121146"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Xiao, Y.W., Zheng, L., Zou, X.F., Wang, J.G., Zhong, J.N., and Zhong, T.Y. (2019). Extracellular vesicles in type 2 diabetes mellitus: Key roles in pathogenesis, complications, and therapy. J. Extracell Vesicles, 8.","DOI":"10.1080\/20013078.2019.1625677"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.2217\/nnm-2020-0099","article-title":"The potential of nanomedicine to alter cancer stem cell dynamics: The impact of extracellular vesicles","volume":"15","author":"Gener","year":"2020","journal-title":"Nanomedicine"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Wang, J.H., Zheng, Y.J., and Zhao, M. (2017). Exosome-Based Cancer Therapy: Implication for Targeting Cancer Stem Cells. Front. Pharmacol., 7.","DOI":"10.3389\/fphar.2016.00533"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1016\/j.bbamem.2014.07.026","article-title":"Examination of the specificity of tumor cell derived exosomes with tumor cells in vitro","volume":"1838","author":"Smyth","year":"2014","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1146\/annurev-cellbio-100818-125300","article-title":"Diverse Cellular Roles of Autophagy","volume":"35","author":"Morishita","year":"2019","journal-title":"Annu Rev. Cell Dev. Biol"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-11718-4","article-title":"Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy","volume":"10","author":"Yong","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Zhang, H.Y., Deng, T., Liu, R., Bai, M., Zhou, L.K., Wang, X., Li, S., Wang, X.Y., Yang, H., and Li, J.L. (2017). Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis. Nat. Commun., 8.","DOI":"10.1038\/ncomms15016"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1002\/mc.23022","article-title":"Exosome-transmitted p120-catenin suppresses hepatocellular carcinoma progression via STAT3 pathways","volume":"58","author":"Cheng","year":"2019","journal-title":"Mol. Carcinog."},{"key":"ref_128","first-page":"151","article-title":"Bladder cancer cellsecreted exosomal miR21 activates the PI3K\/AKT pathway in macrophages to promote cancer progression","volume":"56","author":"Lin","year":"2019","journal-title":"Int J. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Chang, J., Li, H.J., Zhu, Z.C., Mei, P., Hu, W.M., Xiong, X.C., and Tao, J. (2021). microRNA-21-5p from M2 macrophage-derived extracellular vesicles promotes the differentiation and activity of pancreatic cancer stem cells by mediating KLF3. Cell Biol. Toxicol.","DOI":"10.1007\/s10565-021-09597-x"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/cr.2016.53","article-title":"Reversing drug resistance of soft tumor-repopulating cells by tumor cell-derived chemotherapeutic microparticles","volume":"26","author":"Ma","year":"2016","journal-title":"Cell Res."}],"container-title":["Nanomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/7\/1755\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:26:14Z","timestamp":1760163974000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-4991\/11\/7\/1755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":130,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["nano11071755"],"URL":"https:\/\/doi.org\/10.3390\/nano11071755","relation":{},"ISSN":["2079-4991"],"issn-type":[{"value":"2079-4991","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,5]]}}}