{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:58:37Z","timestamp":1791619117948,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Doxorubicin (DOX), an anthracycline chemotherapeutic agent, demonstrates efficacy against various types of cancer. Combining DOX with the antihypertensive drug hydralazine (HDZ) has been proposed as cardioprotective combination therapy, allowing for the use of a reduced DOX dose. The current study describes the remote co-loading of DOX and HDZ into PEGylated liposomes using, for the first time, a simultaneous pH gradient technique. First, PEGylated liposomes were prepared using an ethanol injection method and remotely loaded with DOX and HDZ. Then, DOX- and HDZ-loaded liposomes (Lip-DOX-HDZ) were characterized using DLS, TEM, FTIR, thermal analysis, drug leakage, and stability. Furthermore, the cellular uptake and cytotoxicity were evaluated in two human breast cancer cell lines (MCF7 and MDA-MB-231) and two normal cell lines (human dermal fibroblasts (HDFs) and rat cardiac cells (H9C2)). The results revealed that Lip-DOX-HDZ had a particle size of 158 \u00b1 18 nm, PDI of 0.22 \u00b1 0.08, and zeta potential of \u221222 \u00b1 5 mV. The encapsulation efficiency of DOX and HDZ was 90% and 30%, respectively. Moreover, the IC50 values of Lip-DOX-HDZ showed higher cytotoxicity against the MDA-MB-231 (5.5 \u00b1 0.4 \u00b5M) and MCF7 (6.25 \u00b1 0.9 \u00b5M) breast cancer cell lines compared to normal cells: HDF cells (20 \u00b1 3.0 \u00b5M) and H9C2 cardiac cells (19.37 \u00b1 2.0 \u00b5M). Our study found that remotely loaded Lip-DOX-HDZ showed a ~4-fold lower toxicity and selectivity for normal cells (HDFs and H9C2), compared to breast cancer cells. This suggests that Lip-DOX-HDZ is a promising nanocarrier for both DOX and HDZ, clinically potent molecules.<\/jats:p>","DOI":"10.3390\/molecules30071549","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T05:21:04Z","timestamp":1743398464000},"page":"1549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Remote Co-Loading of Doxorubicin and Hydralazine into PEGylated Liposomes: In Vitro Anti-Proliferative Effect Against Breast Cancer"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2946-7328","authenticated-orcid":false,"given":"Walhan","family":"Alshaer","sequence":"first","affiliation":[{"name":"Cell Therapy Center, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2847-2416","authenticated-orcid":false,"given":"Zainab","family":"Lafi","sequence":"additional","affiliation":[{"name":"Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamdi","family":"Nsairat","sequence":"additional","affiliation":[{"name":"Pharmacological and Diagnostic Research Center, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baidaa","family":"AlQuaissi","sequence":"additional","affiliation":[{"name":"Cell Therapy Center, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana A.","family":"Alqudah","sequence":"additional","affiliation":[{"name":"Cell Therapy Center, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadil","family":"Zureigat","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4326-8624","authenticated-orcid":false,"given":"Islam","family":"Hamad","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, American University of Madaba, Amman 11821, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1093\/annonc\/mdn728","article-title":"Expert opinion on the use of anthracyclines in patients with advanced breast cancer at cardiac risk","volume":"20","author":"Dixon","year":"2009","journal-title":"Ann. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1001\/jama.2018.19323","article-title":"Breast cancer treatment: A review","volume":"321","author":"Waks","year":"2019","journal-title":"JAMA"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1111\/j.2042-7158.2012.01567.x","article-title":"Doxorubicin: An update on anti-cancer molecular action, toxicity and novel drug delivery systems","volume":"65","author":"Tacar","year":"2013","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Davies, G.F., Berg, A., Postnikoff, S.D.L., Wilson, H.L., Arnason, T.G., Kusalik, A., and Harkness, T.A.A. (2014). TFPI1 mediates resistance to doxorubicin in breast cancer cells by inducing a hypoxic-like response. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0084611"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Alshaer, W., Alqudah, D.A., Wehaibi, S., Abuarqoub, D., Zihlif, M., Hatmal, M.M.M., and Awidi, A. (2019). Downregulation of STAT3, \u03b2-catenin, and notch-1 by single and combinations of siRNA treatment enhance chemosensitivity of wild type and doxorubicin resistant MCF7 breast cancer cells to doxorubicin. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20153696"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Argenziano, M., Gigliotti, C.L., Clemente, N., Boggio, E., Ferrara, B., Trotta, F., Pizzimenti, S., Barrera, G., Boldorini, R., and Bessone, F. (2020). Improvement in the anti-tumor efficacy of doxorubicin nanosponges in in vitro and in mice bearing breast tumor models. Cancers, 12.","DOI":"10.3390\/cancers12010162"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Moghimi, S., and Hamad, I. (2009). Factors controlling pharmacokinetics of intravenously injected nanoparticulate systems. Nanotechnology in Drug Delivery, Springer.","DOI":"10.1007\/978-0-387-77668-2_9"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1038\/nm.2919","article-title":"Identification of the molecular basis of doxorubicin-induced cardiotoxicity","volume":"18","author":"Zhang","year":"2012","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Rawat, P.S., Jaiswal, A., Khurana, A., Bhatti, J.S., and Navik, U. (2021). Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed. Pharmacother., 139.","DOI":"10.1016\/j.biopha.2021.111708"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"137414","DOI":"10.1155\/2013\/137414","article-title":"Drug resistance and the role of combination chemotherapy in improving patient outcomes","volume":"2013","author":"Yardley","year":"2013","journal-title":"Int. J. Breast. Cancer"},{"key":"ref_12","first-page":"e18194","article-title":"Association of Cardiotoxicity With Doxorubicin and Trastuzumab: A Double-Edged Sword in Chemotherapy","volume":"13","author":"Gabani","year":"2021","journal-title":"Cureus"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Toews, M.L., and Bylund, D.B. (2005). Pharmacologic principles for combination therapy. Proc. Am. Thorac. Soc., 2.","DOI":"10.1513\/pats.200504-037SR"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Baylin, S.B., and Jones, P.A. (2016). Epigenetic Determinants of Cancer. Cold Spring Harb. Perspect. Biol., 8.","DOI":"10.1101\/cshperspect.a019505"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jconrel.2012.03.020","article-title":"Doxil\u00ae\u2014The first FDA-approved nano-drug: Lessons learned","volume":"160","author":"Barenholz","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"246","DOI":"10.2174\/157489207782497208","article-title":"The efficacy of Caelyx and hyperthermia for anti-cancer treatment","volume":"2","author":"Kouloulias","year":"2007","journal-title":"Recent Pat. Anti-Cancer Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Leporatti, S. (2022). Thinking about Enhanced Permeability and Retention Effect (EPR). J. Pers. Med., 12.","DOI":"10.3390\/jpm12081259"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hamad, I., Harb, A., and Bustanji, Y. (2024). Liposome-Based Drug Delivery Systems in Cancer Research: An Analysis of Global Landscape Efforts and Achievements. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16030400"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xing, M., Yan, F., Yu, S., and Shen, P. (2015). Efficacy and cardiotoxicity of liposomal doxorubicin-based chemotherapy in advanced breast cancer: A meta-analysis of ten randomized controlled trials. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0133569"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1479-5876-4-10","article-title":"Hydralazine target: From blood vessels to the epigenome","volume":"4","author":"Arce","year":"2006","journal-title":"J. Transl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1186\/s13046-019-1160-9","article-title":"Valproic acid exhibits anti-tumor activity selectively against EGFR\/ErbB2\/ErbB3-coexpressing pancreatic cancer via induction of ErbB family members-targeting microRNAs","volume":"38","author":"Lin","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Montalvo-Casimiro, M., Gonzalez-Barrios, R., Meraz-Rodriguez, M.A., Juarez-Gonzalez, V.T., Arriaga-Canon, C., and Herrera, L.A. (2020). Epidrug Repurposing: Discovering New Faces of Old Acquaintances in Cancer Therapy. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.605386"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mello, M.L.S. (2021). Sodium Valproate-Induced Chromatin Remodeling. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.645518"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Ghazi, L., Li, F., Chen, X., Simonov, M., Yamamoto, Y., Biswas, A., Hanna, J., Shah, T., Peixoto, A.J., and Wilson, F.P. (2022). Blood pressure response to commonly administered antihypertensives for severe inpatient hypertension. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0265497"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e321","DOI":"10.1038\/emm.2017.38","article-title":"Methylation and demethylation of DNA and histones in chromatin: The most complicated epigenetic marker","volume":"49","author":"Youn","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1479-5876-4-32","article-title":"Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine","volume":"4","year":"2006","journal-title":"J. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lopes, N., Pacheco, M.B., Soares-Fernandes, D., Correia, M.P., Camilo, V., Henrique, R., and Jer\u00f3nimo, C. (2021). Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer. Biomedicines, 9.","DOI":"10.3390\/biomedicines9080976"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1111\/ajco.13443","article-title":"A clinical trial with valproic acid and hydralazine in combination with gemcitabine and cisplatin followed by doxorubicin and dacarbazine for advanced hepatocellular carcinoma","volume":"18","author":"Liu","year":"2022","journal-title":"Asia-Pac. J. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"21875","DOI":"10.18632\/oncotarget.7871","article-title":"The antihypertensive drug hydralazine activates the intrinsic pathway of apoptosis and causes DNA damage in leukemic T cells","volume":"7","author":"Lucendo","year":"2016","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1161\/01.RES.0000134924.89412.70","article-title":"Novel mechanism of action for hydralazine: Induction of hypoxia-inducible factor-1 \u03b1, vascular endothelial growth factor, and angiogenesis by inhibition of prolyl hydroxylases","volume":"95","author":"Knowles","year":"2004","journal-title":"Circ. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13131","DOI":"10.1200\/jco.2006.24.18_suppl.13131","article-title":"Hydralazine-demethylating systemic therapy for breast cancer","volume":"24","author":"Safar","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_32","first-page":"1751","article-title":"Vasodilator Hydralazine Promotes Nanoparticle Penetration in Advanced Desmoplastic Tumors","volume":"13","author":"Chen","year":"2019","journal-title":"ACS Nano"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1093\/cvr\/cvaa343","article-title":"Hydralazine protects the heart against acute ischaemia\/reperfusion injury by inhibiting Drp1-mediated mitochondrial fission","volume":"118","author":"Kalkhoran","year":"2022","journal-title":"Cardiovasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Chang, T.-T., and Chen, J.-W. (2022). Potential Impacts of Hydralazine as a Novel Antioxidant on Cardiovascular and Renal Disease&mdash;Beyond Vasodilation and Blood Pressure Lowering. Antioxidants, 11.","DOI":"10.3390\/antiox11112224"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"172850","DOI":"10.1016\/j.ejphar.2019.172850","article-title":"Cardioprotection of hydralazine against myocardial ischemia\/reperfusion injury in rats","volume":"869","author":"Li","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lafi, Z., Alshaer, W., Gharaibeh, L., Alqudah, D.A., AlQuaissi, B., Bashaireh, B., and Ibrahim, A.A. (2023). Synergistic combination of doxorubicin with hydralazine, and disulfiram against MCF-7 breast cancer cell line. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0291981"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ibrahim, M., Abuwatfa, W.H., Awad, N.S., Sabouni, R., and Husseini, G.A. (2022). Encapsulation, Release, and Cytotoxicity of Doxorubicin Loaded in Liposomes, Micelles, and Metal-Organic Frameworks: A Review. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14020254"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.2174\/1567201813666151228104643","article-title":"Liposomal Doxorubicin Delivery Systems: Effects of Formulation and Processing Parameters on Drug Loading and Release Behavior","volume":"13","author":"Mohammadi","year":"2016","journal-title":"Curr. Drug Deliv."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1016\/j.sjbs.2020.09.012","article-title":"Enhancing Azithromycin Antibacterial Activity by Encapsulation in Lipo- somes\/Liposomal-N-Acetylcysteine Formulations Against Resistant Clinical Strains of Escherichia coli","volume":"27","author":"Aljihani","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_40","first-page":"104994","article-title":"Preparation of a nanoscale dihydromyricetin-phospholipid complex to improve the bioavailability: In vitro and in vivo evaluations","volume":"138","author":"Zhao","year":"2019","journal-title":"Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci."},{"key":"ref_41","unstructured":"Soliman, G., Fathalla, D., and Fouad, E. (2015). Development and in vitro\/in vivo Evaluation of Liposomal Gels for the Sustained Ocular Delivery of Latanoprost. J. Clin. Exp. Ophthalmol., 6."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"406","DOI":"10.3109\/02652048.2011.576784","article-title":"Preparation of biodegradable nanoparticles of tri-block PLA-PEG-PLA copolymer and determination of factors controlling the particle size using artificial neural network","volume":"28","author":"Asadi","year":"2011","journal-title":"J. Microencapsul."},{"key":"ref_43","unstructured":"Smith, B.C. (1999). Infrared Spectral Interpretation: A Systematic Approach, CRC Press. [1st ed.]."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4218","DOI":"10.1039\/C6CS00636A","article-title":"Cellular uptake of nanoparticles: Journey inside the cell","volume":"46","author":"Behzadi","year":"2017","journal-title":"Chem. Soc. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1111\/jcmm.13110","article-title":"Overviews on the cellular uptake mechanism of polysaccharide colloidal nanoparticles","volume":"21","author":"Salatin","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"636","DOI":"10.2174\/1389201017666160401144440","article-title":"Synergistic combination of doxorubicin and paclitaxel delivered by blood brain barrier and glioma cells dual targeting liposomes for chemotherapy of brain glioma","volume":"17","author":"Chen","year":"2016","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"120358","DOI":"10.1016\/j.talanta.2019.120358","article-title":"Uptake and release profiles of PEGylated liposomal doxorubicin nanoparticles: A comprehensive picture based on separate determination of encapsulated and total drug concentrations in tissues of tumor-bearing mice","volume":"208","author":"Wang","year":"2020","journal-title":"Talanta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.1039\/D3RA08074A","article-title":"Dual stimuli-responsive polymeric nanoparticles combining soluplus and chitosan for enhanced breast cancer targeting","volume":"14","author":"Twal","year":"2024","journal-title":"RSC Adv."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Robson, A.-L., Dastoor, P.C., and Hua, S. (2018). Advantages and limitations of current imaging techniques for characterizing liposome morphology. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.00080"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.tranon.2014.07.003","article-title":"Co-encapsulation of doxorubicin with galactoxyloglucan nanoparticles for intracellular tumor-targeted delivery in murine ascites and solid tumors","volume":"7","author":"Joseph","year":"2014","journal-title":"Transl. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1016\/j.lfs.2004.05.040","article-title":"Mechanism of apoptosis induced by doxorubicin through the generation of hydrogen peroxide","volume":"76","author":"Mizutani","year":"2005","journal-title":"Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41419-021-03614-x","article-title":"Regulated cell death pathways in doxorubicin-induced cardiotoxicity","volume":"12","author":"Christidi","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jpha.2023.08.006","article-title":"Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52","volume":"14","author":"Li","year":"2024","journal-title":"J. Pharm. Anal."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1476-5381.1995.tb14931.x","article-title":"Inhibition of calcium release from the sarcoplasmic reticulum of rabbit aorta by hydralazine","volume":"114","author":"Gurney","year":"1995","journal-title":"Br. J. Pharmacol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1016\/j.bbamem.2014.10.030","article-title":"Ion channels in the regulation of apoptosis","volume":"1848","author":"Kondratskyi","year":"2015","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sukumaran, P., Da Conceicao, V.N., Sun, Y., Ahamad, N., Saraiva, L.R., Selvaraj, S., and Singh, B.B. (2021). Calcium Signaling Regulates Autophagy and Apoptosis. Cells, 10.","DOI":"10.3390\/cells10082125"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Sun, Y., Liu, Y., Ma, X., and Hu, H. (2021). The Influence of Cell Cycle Regulation on Chemotherapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136923"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/S0026-895X(25)09073-X","article-title":"Cell cycle-dependent cytotoxicity, G2\/M phase arrest, and disruption of p34cdc2\/cyclin B1 activity induced by doxorubicin in synchronized P388 cells","volume":"49","author":"Ling","year":"1996","journal-title":"Mol. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4804","DOI":"10.18632\/oncotarget.3103","article-title":"p53 activates G1 checkpoint following DNA damage by doxorubicin during transient mitotic arrest","volume":"6","author":"Hyun","year":"2015","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"J\u00f6nsson, L.\u00d6., Sahi, M., Lopez-Lorenzo, X., Keller, F.L., Kostopoulou, O.N., Herold, N., \u00c4hrlund-Richter, L., and Fard, S.S. (2021). Heterogeneities in cell cycle checkpoint activation following doxorubicin treatment reveal targetable vulnerabilities in Tp53 mutated ultra high-risk neuroblastoma cell lines. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073664"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"30976","DOI":"10.1039\/C9RA05636J","article-title":"Encapsulation of echinomycin in cyclodextrin inclusion complexes into liposomes: In vitro anti-proliferative and anti-invasive activity in glioblastoma","volume":"9","author":"Alshaer","year":"2019","journal-title":"RSC Adv."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"36219","DOI":"10.1039\/D0RA07325C","article-title":"Grafting of anti-nucleolin aptamer into preformed and remotely loaded liposomes through aptamer-cholesterol post-insertion","volume":"10","author":"Nsairat","year":"2020","journal-title":"RSC Adv."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/7\/1549\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:06:30Z","timestamp":1760029590000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/7\/1549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,31]]},"references-count":62,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["molecules30071549"],"URL":"https:\/\/doi.org\/10.3390\/molecules30071549","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,31]]}}}