{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:25:15Z","timestamp":1787678715528,"version":"build-2784847793"},"reference-count":112,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T00:00:00Z","timestamp":1648598400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1903125, 82071986"],"award-info":[{"award-number":["U1903125, 82071986"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Hunan province in China","award":["2021JJ20084"],"award-info":[{"award-number":["2021JJ20084"]}]},{"name":"Science and Technology Innovation Program of Hunan Province","award":["2021RC3020"],"award-info":[{"award-number":["2021RC3020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Arsenic trioxide (ATO) is one of the first-line chemotherapeutic drugs for acute promyelocytic leukemia. Its anti-cancer activities against various human neoplastic diseases have been extensively studied. However, the clinical use of ATO for solid tumors is limited, and these limitations are because of severe systemic toxicity, low bioavailability, and quick renal elimination before it reaches the target site. Although without much success, several efforts have been made to boost ATO bioavailability toward solid tumors without raising its dose. It has been found that nanomedicines have various advantages for drug delivery, including increased bioavailability, effectiveness, dose-response, targeting capabilities, and safety as compared to traditional drugs. Therefore, nanotechnology to deliver ATO to solid tumors is the main topic of this review, which outlines the previous and present medical applications of ATO. We also summarised ATO anti-cancer mechanisms, limitations, and outcomes of combinatorial treatment with chemo agents. As a result, we strongly recommend conducting pre-clinical and clinical studies of ATO, especially nano-system-based ones that might lead to a novel combination therapy for cancer treatment with high efficacy, bioavailability, and low toxicity for cancer patients.<\/jats:p>","DOI":"10.3390\/pharmaceutics14040743","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T21:28:39Z","timestamp":1648675719000},"page":"743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Current Advances of Nanomedicines Delivering Arsenic Trioxide for Enhanced Tumor Therapy"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-5432","authenticated-orcid":false,"given":"Mengzhen","family":"Yu","sequence":"first","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meirong","family":"Fang","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shah","family":"Jehan","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-661X","authenticated-orcid":false,"given":"Wenhu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109624","DOI":"10.1016\/j.biopha.2019.109624","article-title":"Molecular targeted study in tumors: From western medicine to active ingredients of traditional Chinese medicine","volume":"121","author":"Li","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.tips.2013.06.005","article-title":"Cancer drug discovery by repurposing: Teaching new tricks to old dogs","volume":"34","author":"Gupta","year":"2013","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"90","DOI":"10.53388\/TMR20200214164","article-title":"Annual advances in traditional medicine for tumor therapy in 2019","volume":"5","author":"Yang","year":"2020","journal-title":"Tradit. Med. Res."},{"key":"ref_5","first-page":"3358","article-title":"Polysaccharide-based nanomedicines for cancer immunotherapy: A review","volume":"6","author":"Zeng","year":"2021","journal-title":"Bioact. Mater."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5972","DOI":"10.1158\/1078-0432.CCR-10-1277","article-title":"Biologically targeted cancer therapy and marginal benefits: Are we making too much of too little or are we achieving too little by giving too much?","volume":"16","author":"Fojo","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_7","first-page":"1529","article-title":"Metals and metal compounds in cancer treatment","volume":"24","author":"Desoize","year":"2004","journal-title":"Anticancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"177","DOI":"10.7555\/JBR.31.20160059","article-title":"Recent advances in arsenic trioxide encapsulated nanoparticles as drug delivery agents to solid cancers","volume":"31","author":"Akhtar","year":"2017","journal-title":"J. Biomed. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1111\/bjh.14974","article-title":"Realgar nanoparticles versus ATO arsenic compounds induce In Vitro and In Vivo activity against multiple myeloma","volume":"179","author":"Cholujova","year":"2017","journal-title":"Br. J. Haematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1200\/JCO.2005.10.217","article-title":"Arsenic trioxide: New clinical experience with an old medication in hematologic malignancies","volume":"23","author":"Douer","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Sun, T., Zhang, Y.S., Pang, B., Hyun, D.C., Yang, M., and Xia, Y. (2021). Engineered Nanoparticles for Drug Delivery in Cancer Therapy. Nanomaterials and Neoplasms, Jenny Stanford Publishing.","DOI":"10.1201\/9780429027819-2"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.addr.2015.01.002","article-title":"Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity","volume":"91","author":"Maeda","year":"2015","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1021\/acs.bioconjchem.8b00032","article-title":"Direct Polymerization of the Arsenic Drug PENAO to Obtain Nanoparticles with High Thiol-Reactivity and Anti-Cancer Efficiency","volume":"29","author":"Noy","year":"2018","journal-title":"Bioconjug. Chem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104539","DOI":"10.1016\/j.yrtph.2019.104539","article-title":"Arsenic exposure: A public health problem leading to several cancers","volume":"110","year":"2020","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Pullella, K., and Kotsopoulos, J. (2020). Arsenic Exposure and Breast Cancer Risk: A Re-Evaluation of the Literature. Nutrients, 12.","DOI":"10.3390\/nu12113305"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23905","DOI":"10.18632\/oncotarget.14733","article-title":"Metabolism, toxicity and anticancer activities of arsenic compounds","volume":"8","author":"Khairul","year":"2017","journal-title":"Oncotarget"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118438","DOI":"10.1016\/j.lfs.2020.118438","article-title":"An appraisal on molecular and biochemical signalling cascades during arsenic-induced hepatotoxicity","volume":"260","author":"Renu","year":"2020","journal-title":"Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s11658-020-00236-7","article-title":"Arsenic trioxide as a novel anti-glioma drug: A review","volume":"25","author":"Fang","year":"2020","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1182\/blood.V98.5.1632","article-title":"Cardiac toxicity of arsenic trioxide","volume":"98","author":"Barbey","year":"2001","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1126\/science.1183424","article-title":"Arsenic trioxide controls the fate of the PML-RAR alpha oncoprotein by directly binding PML","volume":"328","author":"Zhang","year":"2010","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1080\/10428194.2017.1346253","article-title":"Arsenic trioxide decreases the amount and inhibits the function of regulatory T cells, which may contribute to its efficacy in the treatment of acute promyelocytic leukemia","volume":"59","author":"Xu","year":"2018","journal-title":"Leuk. Lymphoma"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1039\/C8MT00202A","article-title":"Arsenic trioxide preferentially binds to the ring finger protein PML: Understanding target selection of the drug","volume":"10","author":"Cao","year":"2018","journal-title":"Metallomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/08880018.2021.1872748","article-title":"Arsenic trioxide in pediatric cancer\u2014A case series and review of literature","volume":"38","author":"Abele","year":"2021","journal-title":"Pediatr. Hematol. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2019.08.009","article-title":"Arsenic trioxide inhibits angiogenesis In Vitro and In Vivo by upregulating FoxO3a","volume":"315","author":"Sun","year":"2019","journal-title":"Toxicol. Lett."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1477-7819-8-31","article-title":"Research The conformation change of Bcl-2 is involved in arsenic trioxide-induced apoptosis and inhibition of proliferation in SGC7901 human gastric cancer cells","volume":"8","author":"Zheng","year":"2010","journal-title":"World J. Surg. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fphar.2020.00123","article-title":"Ascorbic Acid Sensitizes Colorectal Carcinoma to the Cytotoxicity of Arsenic Trioxide via Promoting Reactive Oxygen Species-Dependent Apoptosis and Pyroptosis","volume":"11","author":"Tian","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.pneurobio.2006.07.006","article-title":"The paradoxical pro- and anti-apoptotic actions of GSK3 in the intrinsic and extrinsic apoptosis signaling pathways","volume":"79","author":"Beurel","year":"2006","journal-title":"Prog. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s12094-019-02054-6","article-title":"A candidate for lung cancer treatment: Arsenic trioxide","volume":"21","author":"Huang","year":"2019","journal-title":"Clin. Transl. Oncol."},{"key":"ref_29","first-page":"4875","article-title":"Mechanism of As2O3 induces apoptosis of glioma U87 cells","volume":"21","author":"Wang","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_30","first-page":"3341","article-title":"Arsenic trioxide and sorafenib combination therapy for human hepatocellular carcinoma functions via up-regulation of TNF-related apoptosis-inducing ligand","volume":"16","author":"Wang","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.mrgentox.2014.04.016","article-title":"Critical role of cellular glutathione homeostasis for trivalent inorganic arsenite-induced oxidative damage in human bronchial epithelial cells","volume":"770","author":"Jiang","year":"2014","journal-title":"Mutat. Res. Genet. Toxicol. Environ. Mutagen."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s11658-018-0074-4","article-title":"Arsenic trioxide induces apoptosis and the formation of reactive oxygen species in rat glioma cells","volume":"23","author":"Sun","year":"2018","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1101\/gad.272278.115","article-title":"Atomic structure of the apoptosome: Mechanism of cytochrome c-and dATP-mediated activation of Apaf-1","volume":"29","author":"Zhou","year":"2015","journal-title":"Genes Dev."},{"key":"ref_34","first-page":"1067","article-title":"Arsenic trioxide-induced cytotoxicity in small cell lung cancer via altered redox homeostasis and mitochondrial integrity","volume":"46","author":"Zheng","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.freeradbiomed.2017.02.015","article-title":"Arsenic sulfide induces apoptosis and autophagy through the activation of ROS\/JNK and suppression of Akt\/mTOR signaling pathways in osteosarcoma","volume":"106","author":"Wang","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1007\/s00125-016-4058-5","article-title":"Survival or death: A dual role for autophagy in stress-induced pericyte loss in diabetic retinopathy","volume":"59","author":"Fu","year":"2016","journal-title":"Diabetologia"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.bbrc.2018.01.018","article-title":"Arsenic trioxide induces autophagic cell death in osteosarcoma cells via the ROS-TFEB signaling pathway","volume":"496","author":"Wu","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"17523","DOI":"10.1038\/s41598-021-96822-6","article-title":"Arsenic leads to autophagy of keratinocytes by increasing aquaporin 3 expression","volume":"11","author":"Yu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4347","DOI":"10.1038\/s41467-018-06749-2","article-title":"Nanodiamond autophagy inhibitor allosterically improves the arsenical-based therapy of solid tumors","volume":"9","author":"Cui","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1007\/s12272-019-01190-5","article-title":"Potential molecular mechanisms underlying the effect of arsenic on angiogenesis","volume":"42","author":"Zhang","year":"2019","journal-title":"Arch. Pharmacal Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/nrd2792","article-title":"The FGF family: Biology, pathophysiology and therapy","volume":"8","author":"Beenken","year":"2009","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1684\/ecn.2009.0170","article-title":"VEGF-A: A critical regulator of blood vessel growth","volume":"20","author":"Ferrara","year":"2009","journal-title":"Eur. Cytokine Netw."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Zhang, L., Liu, L., Zhan, S.N., Chen, L.L., Wang, Y.Y., Zhang, Y.J., Du, J., Wu, Y.P., and Gu, L. (2018). Arsenic Trioxide Suppressed Migration and Angiogenesis by Targeting FOXO3a in Gastric Cancer Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123739"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1039\/C8BM01039K","article-title":"Facile synthesis of aquo-cisplatin arsenite multidrug nanocomposites for overcoming drug resistance and efficient combination therapy","volume":"7","author":"Xin","year":"2018","journal-title":"Biomater. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1007\/s12272-018-1014-6","article-title":"Realgar transforming solution suppresses angiogenesis and tumor growth by inhibiting VEGF receptor 2 signaling in vein endothelial cells","volume":"41","author":"Song","year":"2018","journal-title":"Arch. Pharm. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3748","DOI":"10.3892\/ol.2017.6646","article-title":"Tumour growth-suppressive effect of arsenic trioxide in squamous cell lung carcinoma","volume":"14","author":"Leung","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Laka, K., Makgoo, L., and Mbita, Z. (2019). Survivin Splice Variants in Arsenic Trioxide (As\u2082O\u2083)-Induced Deactivation of PI3K and MAPK Cell Signalling Pathways in MCF-7 Cells. Genes, 10.","DOI":"10.3390\/genes10010041"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1010428317692255","DOI":"10.1177\/1010428317692255","article-title":"Demethylation and alterations in the expression level of the cell cycle-related genes as possible mechanisms in arsenic trioxide-induced cell cycle arrest in human breast cancer cells","volume":"39","author":"Moghaddaskho","year":"2017","journal-title":"Tumor Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s00277-017-3163-y","article-title":"Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB4)","volume":"97","author":"Hassani","year":"2018","journal-title":"Ann. Hematol."},{"key":"ref_50","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_51","first-page":"4008","article-title":"Effect of As2O3 on colorectal CSCs stained with ALDH1 in primary cell culture In Vitro","volume":"16","author":"Ning","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_52","first-page":"1133","article-title":"Arsenic trioxide inhibits cancer stem-like cells via down-regulation of Gli1 in lung cancer","volume":"8","author":"Chang","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Chang, Q., Bi, Z., Fu, Y., Rice, M., Zhang, Q., Wadgaonkar, P., Almutairy, B., Zhang, W., Lu, Y., and Xu, L. (2020). Characterization of arsenic-induced cancer stem-like cells. Stem Cell Transcriptional Networks, Springer.","DOI":"10.1007\/978-1-0716-0301-7_19"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Linder, B., Wehle, A., Hehlgans, S., Bonn, F., Dikic, I., Rodel, F., Seifert, V., and Kogel, D. (2019). Arsenic Trioxide and (\u2212)-Gossypol Synergistically Target Glioma Stem-Like Cells via Inhibition of Hedgehog and Notch Signaling. Cancers, 11.","DOI":"10.3390\/cancers11030350"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41419-019-1676-0","article-title":"Arsenic trioxide inhibits liver cancer stem cells and metastasis by targeting SRF\/MCM7 complex","volume":"10","author":"Wang","year":"2019","journal-title":"Cell Death Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.ijpharm.2017.01.031","article-title":"RGD conjugated liposome-hollow silica hybrid nanovehicles for targeted and controlled delivery of arsenic trioxide against hepatic carcinoma","volume":"519","author":"Fei","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1517\/14740338.3.6.589","article-title":"Arsenic trioxide in the treatment of haematological malignancies","volume":"3","author":"Kwong","year":"2004","journal-title":"Expert Opin. Drug Safety"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.taap.2019.05.006","article-title":"Review of arsenic toxicity, speciation and polyadenylation of canonical histones","volume":"375","author":"Costa","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s40572-014-0012-1","article-title":"The effects of arsenic exposure on neurological and cognitive dysfunction in human and rodent studies: A review","volume":"1","author":"Tyler","year":"2014","journal-title":"Curr. Environ. Health Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"143941","DOI":"10.1016\/j.gene.2019.143941","article-title":"Analysis of the dynamic aberrant landscape of DNA methylation and gene expression during arsenic-induced cell transformation","volume":"711","author":"Rangel","year":"2019","journal-title":"Gene"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1093\/toxsci\/kfy176","article-title":"Arsenic Alters Exosome Quantity and Cargo to Mediate Stem Cell Recruitment Into a Cancer Stem Cell-Like Phenotype","volume":"165","author":"Ngalame","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.colsurfb.2018.05.024","article-title":"Effects of surface modification of As2O3-loaded PLGA nanoparticles on its anti-liver cancer ability: An In Vitro and In Vivo study","volume":"169","author":"Song","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.ajps.2018.12.002","article-title":"Arsenic trioxide encapsulated liposomes prepared via copper acetate gradient loading method and its antitumor efficiency","volume":"15","author":"Wang","year":"2020","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"132","DOI":"10.18433\/jpps30583","article-title":"Targeted Nanomedicines for Cancer Therapy, From Basics to Clinical Trials","volume":"23","author":"Eskandari","year":"2020","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"8016","DOI":"10.1021\/acsami.9b22802","article-title":"Delivery of Arsenic Trioxide by Multifunction Nanoparticles to Improve the Treatment of Hepatocellular Carcinoma","volume":"12","author":"Wu","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1158\/1535-7163.MCT-09-0045","article-title":"Folate-mediated intracellular drug delivery increases the anticancer efficacy of nanoparticulate formulation of arsenic trioxide","volume":"8","author":"Chen","year":"2009","journal-title":"Mol. Cancer Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbrc.2021.02.138","article-title":"Angiopep-2-modified calcium arsenite-loaded liposomes for targeted and pH-responsive delivery for anti-glioma therapy","volume":"551","author":"Xu","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1007\/s12668-020-00726-0","article-title":"Synthesis and Characterization of Arsenic(III) Oxide Nanoparticles as Potent Inhibitors of MCF 7 Cell Proliferation through Proapoptotic Mechanism","volume":"10","author":"Das","year":"2020","journal-title":"BioNanoScience"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1080\/10717544.2020.1856219","article-title":"Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal","volume":"27","author":"Kong","year":"2020","journal-title":"Drug Deliv."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e2102054","DOI":"10.1002\/adma.202102054","article-title":"Arsenene Nanodots with Selective Killing Effects and their Low-Dose Combination with ss-Elemene for Cancer Therapy","volume":"33","author":"Liu","year":"2021","journal-title":"Adv. Mater."},{"key":"ref_71","first-page":"1","article-title":"Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression","volume":"20","author":"Chen","year":"2022","journal-title":"J. Nanobiotechnol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"445101","DOI":"10.1088\/1361-6528\/aa8791","article-title":"Arsenite-loaded nanoparticles inhibit the invasion and metastasis of a hepatocellular carcinoma: In Vitro and In Vivo study","volume":"28","author":"Chi","year":"2017","journal-title":"Nanotechnology"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Akhtar, A., Ghali, L., Wang, S.X., Bell, C., Li, D., and Wen, X. (2019). Optimisation of Folate-Mediated Liposomal Encapsulated Arsenic Trioxide for Treating HPV-Positive Cervical Cancer Cells In Vitro. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20092156"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1158\/1078-0432.CCR-10-0068","article-title":"A novel nanoparticulate formulation of arsenic trioxide with enhanced therapeutic efficacy in a murine model of breast cancer","volume":"16","author":"Ahn","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1179\/joc.2008.20.2.253","article-title":"Intravenous administration of arsenic trioxide encapsulated in liposomes inhibits the growth of C6 gliomas in rat brains","volume":"20","author":"Zhao","year":"2008","journal-title":"J. Chemother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.2147\/IJN.S313962","article-title":"Liposome-Coated Arsenic-Manganese Complex for Magnetic Resonance Imaging-Guided Synergistic Therapy against Carcinoma","volume":"16","author":"Jin","year":"2021","journal-title":"Int. J. Nanomed."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"13348","DOI":"10.1021\/ja064864h","article-title":"Lipid encapsulation of arsenic trioxide attenuates cytotoxicity and allows for controlled anticancer drug release","volume":"128","author":"Chen","year":"2006","journal-title":"J. Am. Chem. Soc."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8031","DOI":"10.1039\/C7NR09503A","article-title":"Investigation of HSA as a biocompatible coating material for arsenic trioxide nanoparticles","volume":"10","author":"Hoonjan","year":"2018","journal-title":"Nanoscale"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40591-016-0048-8","article-title":"Albumin-based drug delivery: Harnessing nature to cure disease","volume":"4","author":"Larsen","year":"2016","journal-title":"Mol. Cell. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/2008-2231-21-58","article-title":"Surface modification of PLGA nanoparticles via human serum albumin conjugation for controlled delivery of docetaxel","volume":"21","author":"Manoochehri","year":"2013","journal-title":"DARU J. Pharm. Sci."},{"key":"ref_81","first-page":"80","article-title":"Bovine Serum Albumin-Conjugated Ferrimagnetic Iron Oxide Nanoparticles to Enhance the Biocompatibility and Magnetic Hyperthermia Performance","volume":"8","author":"Kalidasan","year":"2016","journal-title":"Nanomicro Lett."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1080\/03639040801926733","article-title":"Evaluation of arsenic trioxide-loaded albumin nanoparticles as carriers: Preparation and antitumor efficacy","volume":"34","author":"Yang","year":"2008","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"10845","DOI":"10.1002\/anie.201701366","article-title":"Smart human-serum-albumin\u2013As2O3 nanodrug with self-amplified folate receptor-targeting ability for chronic myeloid leukemia treatment","volume":"56","author":"Peng","year":"2017","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_84","first-page":"415289","article-title":"Bone regeneration from PLGA micro-nanoparticles","volume":"2015","year":"2015","journal-title":"BioMed Res. Int."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"11079","DOI":"10.1021\/acs.chemrev.5b00125","article-title":"Nanomedicine applications of hybrid nanomaterials built from metal\u2013ligand coordination bonds: Nanoscale metal\u2013organic frameworks and nanoscale coordination polymers","volume":"115","author":"He","year":"2015","journal-title":"Chem. Rev."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"13189","DOI":"10.1002\/chem.201902599","article-title":"Zeolitic Imidazolate Framework-8 as pH-Sensitive Nanocarrier for \u201cArsenic Trioxide\u201d Drug Delivery","volume":"25","author":"Ettlinger","year":"2019","journal-title":"Chemistry"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6313","DOI":"10.1039\/C4TB00874J","article-title":"Silica nanovehicles endow arsenic trioxide with an ability to effectively treat cancer cells and solid tumors","volume":"2","author":"Zhao","year":"2014","journal-title":"J. Mater. Chem. B"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12951-015-0068-6","article-title":"Lactosaminated mesoporous silica nanoparticles for asialoglycoprotein receptor targeted anticancer drug delivery","volume":"13","author":"Quan","year":"2015","journal-title":"J. Nanobiotechnol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"119385","DOI":"10.1016\/j.ijpharm.2020.119385","article-title":"Construction of arsenic-metal complexes loaded nanodrugs for solid tumor therapy: A mini review","volume":"583","author":"Fei","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1093\/annonc\/mdw171","article-title":"Current management of newly diagnosed acute promyelocytic leukemia","volume":"27","author":"Cicconi","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jconrel.2017.02.020","article-title":"Nanodrug delivery systems for targeting the endogenous tumor microenvironment and simultaneously overcoming multidrug resistance properties","volume":"251","author":"Li","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"152947","DOI":"10.1016\/j.phymed.2019.152947","article-title":"Tooniliatone A sensitizes multidrug resistant cancer cells by decreasing Bcl-xL via activation of JNK MAPK signaling","volume":"62","author":"Li","year":"2019","journal-title":"Phytomedicine"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1055\/s-0032-1328554","article-title":"Arsenic trioxide-enhanced, matrine-induced apoptosis in multiple myeloma cell lines","volume":"79","author":"Yu","year":"2013","journal-title":"Planta Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.ejphar.2017.12.041","article-title":"Targeting of EGFR increase anti-cancer effects of arsenic trioxide: Promising treatment for glioblastoma multiform","volume":"820","author":"Mesbahi","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jconrel.2021.08.035","article-title":"Imatinib co-loaded targeted realgar nanocrystal for synergistic therapy of chronic myeloid leukemia","volume":"338","author":"Wang","year":"2021","journal-title":"J. Control. Release"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1080\/0284186X.2019.1630750","article-title":"Arsenic trioxide and tetraarsenic oxide induce cytotoxicity and have a synergistic effect with cisplatin in paclitaxel-resistant ovarian cancer cells","volume":"58","author":"Byun","year":"2019","journal-title":"Acta Oncologica"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1111\/jcmm.13436","article-title":"Combination of arsenic trioxide and Dasatinib: A new strategy to treat Philadelphia chromosome-positive acute lymphoblastic leukaemia","volume":"22","author":"Wang","year":"2018","journal-title":"J. Cell. Mol. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"97","DOI":"10.14715\/cmb\/2019.65.4.16","article-title":"Effect of combination of all-trans retinoic acid and arsenic trioxide on apoptosis of acute promyelocytic leukemia cells","volume":"65","author":"Hu","year":"2019","journal-title":"Cell. Mol. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"10749","DOI":"10.1002\/anie.201303251","article-title":"Robust Structure and Reactivity of Aqueous Arsenous Acid-Platinum(II) Anticancer Complexes","volume":"52","author":"Miodragovic","year":"2013","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_100","first-page":"3404","article-title":"Synergistic effect of arsenic trioxide, vismodegib and temozolomide on glioblastoma","volume":"41","author":"Bureta","year":"2019","journal-title":"Oncol. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1007\/s11064-011-0620-1","article-title":"Synergistic effects of arsenic trioxide and silibinin on apoptosis and invasion in human glioblastoma U87MG cell line","volume":"37","author":"Dizaji","year":"2012","journal-title":"Neurochem. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1038\/s41401-021-00648-x","article-title":"Lipid\/PAA-coated mesoporous silica nanoparticles for dual-pH-responsive codelivery of arsenic trioxide\/paclitaxel against breast cancer cells","volume":"42","author":"Zhang","year":"2021","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.canlet.2016.07.007","article-title":"Arsenic trioxide induces Noxa-dependent apoptosis in rhabdomyosarcoma cells and synergizes with antimicrotubule drugs","volume":"381","author":"Meister","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.fct.2014.02.039","article-title":"Additivity, antagonism, and synergy in arsenic trioxide-induced growth inhibition of C6 glioma cells: Effects of genistein, quercetin and buthionine-sulfoximine","volume":"67","author":"Klauser","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_105","first-page":"1401","article-title":"Combination treatment with arsenic trioxide and sulindac augments their apoptotic potential in lung cancer cells through activation of caspase cascade and mitochondrial dysfunction","volume":"28","author":"Kim","year":"2006","journal-title":"Int. J. Oncol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"237543","DOI":"10.1155\/2013\/237543","article-title":"Indomethacin-enhanced anticancer effect of arsenic trioxide in A549 cell line: Involvement of apoptosis and phospho-ERK and p38 MAPK pathways","volume":"2013","author":"Mandegary","year":"2013","journal-title":"BioMed Res. Int."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.nano.2013.08.007","article-title":"Combination of siRNA-directed Kras oncogene silencing and arsenic-induced apoptosis using a nanomedicine strategy for the effective treatment of pancreatic cancer","volume":"10","author":"Zeng","year":"2014","journal-title":"Nanomed. Nanotechnol. Biol. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"386","DOI":"10.7150\/ijbs.28356","article-title":"Synergistic anti-tumor effects of arsenic trioxide and blue LED irradiation on human osteosarcoma","volume":"15","author":"Feng","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"271","DOI":"10.17219\/acem\/81610","article-title":"The new perspectives of targeted therapy in acute myeloid leukemia","volume":"28","author":"Walasek","year":"2019","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"108665","DOI":"10.1016\/j.biopha.2019.108665","article-title":"Pre-application of arsenic trioxide may potentiate cytotoxic effects of vinorelbine\/docetaxel on neuroblastoma SK-N-SH cells","volume":"113","author":"Qi","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_111","first-page":"566","article-title":"Arsenic trioxide cytotoxicity in steroid and chemotherapy-resistant myeloma cell lines: Enhancement of apoptosis by manipulation of cellular redox state","volume":"8","author":"Gartenhaus","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1081\/LPR-120039661","article-title":"Arsenic trioxide liposomes: Encapsulation efficiency and In Vitro stability","volume":"14","author":"Kallinteri","year":"2004","journal-title":"J. Liposome Res."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/4\/743\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:46:15Z","timestamp":1760136375000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/4\/743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,30]]},"references-count":112,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,4]]}},"alternative-id":["pharmaceutics14040743"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14040743","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,30]]}}}