{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:29:42Z","timestamp":1790713782595,"version":"4.1.0"},"reference-count":64,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alexander von Humboldt Foundation, Germany"},{"name":"Open Access Publishing Fund of Philipps-Universit\u00e4t Marburg"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chemoresistance encountered using conventional chemotherapy demands novel treatment approaches. Asplatin (Asp), a novel platinum (IV) prodrug designed to release cisplatin and aspirin in a reductive environment, has demonstrated high cytotoxicity at reduced drug resistance. Herein, we investigated the ability of green-synthesized nanocarriers to enhance Asp\u2019s efficacy. Zinc oxide nanoparticles (ZnO-NPs) were synthesized using a green microwave-assisted method with the reducing and capping agent gambogic acid (GA). These nanoparticles were then loaded with Asp, yielding Asp@ZnO-NPs. Transmission electron microscopy was utilized to study the morphological features of ZnO-NPs. Cell viability studies conducted on MDA-MB-231 breast cancer cells demonstrated the ability of the Asp@ZnO-NPs treatment to significantly decrease Asp\u2019s half-maximal inhibitory concentration (IC50) (5 \u00b1 1 \u00b5g\/mL). This was further demonstrated using flow cytometric analysis that revealed the capacity of Asp@ZnO-NPs treatment to significantly increase late apoptotic fractions. Furthermore, in vivo studies carried out using solid Ehrlich carcinoma-bearing mice showed significant tumor volume reduction with the Asp@ZnO-NPs treatment (156.3 \u00b1 7.6 mm3), compared to Asp alone (202.3 \u00b1 8.4 mm3) and untreated controls (342.6 \u00b1 10.3 mm3). The histopathological analysis further demonstrated the increased necrosis in Asp@ZnO-NPs-treated group. This study revealed that Asp@ZnO-NPs, synthesized using an eco-friendly approach, significantly enhanced Asp\u2019s anticancer activity, offering a sustainable solution for potent anticancer formulations.<\/jats:p>","DOI":"10.3390\/molecules29225327","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T08:12:39Z","timestamp":1731399159000},"page":"5327","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Sustainable Nanomedicine: Enhancement of Asplatin\u2019s Cytotoxicity In Vitro and In Vivo Using Green-Synthesized Zinc Oxide Nanoparticles Formed via Microwave-Assisted and Gambogic Acid-Mediated Processes"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7493-8564","authenticated-orcid":false,"given":"Hatem A. F. M.","family":"Hassan","sequence":"first","affiliation":[{"name":"Medway School of Pharmacy, University of Kent, Chatham Maritime, Kent ME4 4TB, UK"},{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2359-3799","authenticated-orcid":false,"given":"Nada K.","family":"Sedky","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, Cairo 11835, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4454-6390","authenticated-orcid":false,"given":"Mohamed S.","family":"Nafie","sequence":"additional","affiliation":[{"name":"Department of Chemistry, College of Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1486-3507","authenticated-orcid":false,"given":"Noha Khalil","family":"Mahdy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"},{"name":"School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, Cairo 11835, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iten M.","family":"Fawzy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Future University in Egypt, Cairo 11835, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0922-185X","authenticated-orcid":false,"given":"Toka Waleed","family":"Fayed","sequence":"additional","affiliation":[{"name":"School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, Cairo 11835, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2112-8436","authenticated-orcid":false,"given":"Eduard","family":"Preis","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3895-0453","authenticated-orcid":false,"given":"Udo","family":"Bakowsky","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-8281","authenticated-orcid":false,"given":"Sherif Ashraf","family":"Fahmy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s12032-023-02138-y","article-title":"Cancer chemoresistance and its mechanisms: Associated molecular factors and its regulatory role","volume":"40","author":"Kannampuzha","year":"2023","journal-title":"Med. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bukowski, K., Kciuk, M., and Kontek, R. (2020). Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21093233"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6013","DOI":"10.1021\/acs.inorgchem.7b00945","article-title":"Hydrolysis in Acidic Environment and Degradation of Satraplatin: A Joint Experimental and Theoretical Investigation","volume":"56","author":"Ritacco","year":"2017","journal-title":"Inorg. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nrc2167","article-title":"The resurgence of platinum-based cancer chemotherapy","volume":"7","author":"Kelland","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41568-020-00308-y","article-title":"The rediscovery of platinum-based cancer therapy","volume":"21","author":"Rottenberg","year":"2021","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Fahmy, S.A., Ponte, F., Grande, G., Fawzy, I.M., Mandour, A.A., Sicilia, E., and Azzazy, H.M.E.-S. (2022). Synthesis, Characterization and Host-Guest Complexation of Asplatin: Improved In Vitro Cytotoxicity and Biocompatibility as Compared to Cisplatin. Pharmaceuticals, 15.","DOI":"10.3390\/ph15020259"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41416-023-02506-5","article-title":"Aspirin and cancer treatment: Systematic reviews and meta-analyses of evidence: For and against","volume":"130","author":"Elwood","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.3390\/ph5121346","article-title":"Mechanistic and Pharmacological Issues of Aspirin as an Anticancer Agent","volume":"5","author":"Dovizio","year":"2012","journal-title":"Pharmaceuticals"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.2174\/1381612826666201102101758","article-title":"Current Studies of Aspirin as an Anticancer Agent and Strategies to Strengthen its Therapeutic Application in Cancer","volume":"27","author":"Tran","year":"2021","journal-title":"Curr. Pharm. Des."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Elwood, P., Protty, M., Morgan, G., Pickering, J., Delon, C., and Watkins, J. (2022). Aspirin and cancer: Biological mechanisms and clinical outcomes. Open Biol., 12.","DOI":"10.1098\/rsob.220124"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"87379","DOI":"10.18632\/oncotarget.20972","article-title":"Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells","volume":"8","author":"Gu","year":"2017","journal-title":"Oncotarget"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1039\/C6MT00066E","article-title":"Asplatin enhances drug efficacy by altering the cellular response\u2020","volume":"8","author":"Cheng","year":"2016","journal-title":"Metallomics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7427","DOI":"10.1039\/C4CC00419A","article-title":"The ligation of aspirin to cisplatin demonstrates significant synergistic effects on tumor cells","volume":"50","author":"Cheng","year":"2014","journal-title":"Chem. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.1039\/D4MA00075G","article-title":"From antigen uptake to immune modulation: The multifaceted potential of peptide nanofibers as vaccine nanocarriers","volume":"5","author":"Hassan","year":"2024","journal-title":"Mater. Adv."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Paveli\u0107, K., Kraljevi\u0107 Paveli\u0107, S., Bulog, A., Agaj, A., Rojni\u0107, B., \u010coli\u0107, M., and Trivanovi\u0107, D. (2023). Nanoparticles in Medicine: Current Status in Cancer Treatment. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612827"},{"key":"ref_16","first-page":"20","article-title":"Formulation considerations and factors affecting transdermal drug delivery system\u2014A review","volume":"2","author":"Shabbir","year":"2014","journal-title":"Int. J. Pharm. Integr. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Szwed, M., and Marczak, A. (2024). Application of Nanoparticles for Magnetic Hyperthermia for Cancer Treatment\u2014The Current State of Knowledge. Cancers, 16.","DOI":"10.3390\/cancers16061156"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Oehler, J.B., Rajapaksha, W., and Albrecht, H. (2024). Emerging Applications of Nanoparticles in the Diagnosis and Treatment of Breast Cancer. J. Pers. Med., 14.","DOI":"10.3390\/jpm14070723"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jconrel.2021.03.002","article-title":"PD1 blockade potentiates the therapeutic efficacy of photothermally-activated and MRI-guided low temperature-sensitive magnetoliposomes","volume":"332","author":"Ma","year":"2021","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Giordano, A., Provenza, A.C., Reverchon, G., Baldino, L., and Reverchon, E. (2024). Lipid-Based Nanocarriers: Bridging Diagnosis and Cancer Therapy. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16091158"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1021\/acsomega.2c06390","article-title":"Essential Oils Extracted from Boswellia sacra Oleo Gum Resin Loaded into PLGA\u2013PCL Nanoparticles: Enhanced Cytotoxic and Apoptotic Effects against Breast Cancer Cells","volume":"8","author":"Azzazy","year":"2023","journal-title":"ACS Omega"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5399","DOI":"10.1039\/D3NA00368J","article-title":"Box\u2013Behnken design of thermo-responsive nano-liposomes loaded with a platinum(iv) anticancer complex: Evaluation of cytotoxicity and apoptotic pathways in triple negative breast cancer cells","volume":"5","author":"Sedky","year":"2023","journal-title":"Nanoscale Adv."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sell, M., Lopes, A.R., Escudeiro, M., Esteves, B., Monteiro, A.R., Trindade, T., and Cruz-Lopes, L. (2023). Application of Nanoparticles in Cancer Treatment: A Concise Review. Nanomaterials, 13.","DOI":"10.20944\/preprints202310.0609.v1"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Fahmy, S.A., Sedky, N.K., Hassan, H.A.F.M., Abdel-Kader, N.M., Mahdy, N.K., Amin, M.U., Preis, E., and Bakowsky, U. (2024). Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16101282"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Anjum, S., Hashim, M., Malik, S.A., Khan, M., Lorenzo, J.M., Abbasi, B.H., and Hano, C. (2021). Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment. Cancers, 13.","DOI":"10.3390\/cancers13184570"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4973","DOI":"10.1039\/D0TB00739K","article-title":"Zinc oxide nanoparticles for therapeutic purposes in cancer medicine","volume":"8","author":"Wiesmann","year":"2020","journal-title":"J. Mater. Chem. B"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"672","DOI":"10.3109\/21691401.2014.978980","article-title":"Development and characterization of metal oxide nanoparticles for the delivery of anticancer drug","volume":"44","author":"Sharma","year":"2016","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1021\/acs.molpharmaceut.6b00311","article-title":"Zinc Oxide Nanoparticles as Adjuvant To Facilitate Doxorubicin Intracellular Accumulation and Visualize pH-Responsive Release for Overcoming Drug Resistance","volume":"13","author":"Liu","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/bio.3180","article-title":"Synthesis of ZnO nanoparticles using a hydrothermal method and a study its optical activity","volume":"32","author":"Bharti","year":"2017","journal-title":"Luminescence"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/s11051-021-05145-0","article-title":"Generation of ZnO nanoparticles by chemical vapor synthesis using quenching air","volume":"23","author":"Jia","year":"2021","journal-title":"J. Nanoparticle Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1016\/j.saa.2011.05.019","article-title":"Photoconductivity and photoluminescence of ZnO nanoparticles synthesized via co-precipitation method","volume":"79","author":"Kripal","year":"2011","journal-title":"Spectrochim. Acta Part A Mol. Biomol. Spectrosc."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ruan, M., Wang, X., Guo, M., Hu, Z., Hu, W., Guo, Z., Chen, W., Li, S., Wu, K., and Du, S. (2025). Gambogic acid and IR780 self-assembled nanoparticles for combined chemo-phototherapy. Colloids Surf. B Biointerfaces, 245.","DOI":"10.1016\/j.colsurfb.2024.114254"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1007\/s10311-021-01319-3","article-title":"Green synthesis of metal nanoparticles using Garcinia extracts: A review","volume":"20","author":"Sarip","year":"2022","journal-title":"Environ. Chem. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1007\/s12034-018-1568-4","article-title":"Green synthesis of zinc oxide nanoparticles using aqueous extract of Garcinia mangostana fruit pericarp and their photocatalytic activity","volume":"41","author":"Aminuzzaman","year":"2018","journal-title":"Bull. Mater. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s11671-022-03678-4","article-title":"Facile Green Synthesis of Titanium Dioxide Nanoparticles by Upcycling Mangosteen (Garcinia mangostana) Pericarp Extract","volume":"17","author":"Ahn","year":"2022","journal-title":"Nanoscale Res. Lett."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1007\/s12011-020-02138-3","article-title":"Green Synthesis of Metallic Nanoparticles and Their Prospective Biotechnological Applications: An Overview","volume":"199","author":"Salem","year":"2021","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9709","DOI":"10.1039\/C4DT03222E","article-title":"Biogenic synthesis of metallic nanoparticles and prospects toward green chemistry","volume":"44","author":"Adil","year":"2015","journal-title":"Dalton Trans."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Dikshit, P.K., Kumar, J., Das, A.K., Sadhu, S., Sharma, S., Singh, S., Gupta, P.K., and Kim, B.S. (2021). Green Synthesis of Metallic Nanoparticles: Applications and Limitations. Catalysts, 11.","DOI":"10.3390\/catal11080902"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1007\/s10854-019-02612-2","article-title":"Facile microwave-assisted green synthesis of ZnO nanoparticles: Application to photodegradation, antibacterial and antioxidant","volume":"31","author":"Mallikarjunaswamy","year":"2020","journal-title":"J. Mater. Sci. Mater. Electron."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7228","DOI":"10.1021\/acsapm.2c01093","article-title":"Peganum harmala Alkaloids and Tannic Acid Encapsulated in PAMAM Dendrimers: Improved Anticancer Activities as Compared to Doxorubicin","volume":"4","author":"Azzazy","year":"2022","journal-title":"ACS Appl. Polym. Mater."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/j.xphs.2021.12.016","article-title":"Pharmacokinetic and Pharmacodynamic Evaluation of Gemifloxacin Chitosan Nanoparticles As an Antibacterial Ocular Dosage Form","volume":"111","author":"Hassan","year":"2022","journal-title":"J. Pharm. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sarkar, J., Chakraborty, N., Chatterjee, A., Bhattacharjee, A., Dasgupta, D., and Acharya, K. (2020). Green Synthesized Copper Oxide Nanoparticles Ameliorate Defence and Antioxidant Enzymes in Lens culinaris. Nanomaterials, 10.","DOI":"10.3390\/nano10020312"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s42452-020-2813-1","article-title":"Green synthesis and characterization of zinc oxide nanoparticles using Eucalyptus globulus Labill. leaf extract and zinc nitrate hexahydrate salt","volume":"2","author":"Barzinjy","year":"2020","journal-title":"SN Appl. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1200\/JCO.1999.17.1.409","article-title":"Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin","volume":"17","author":"Go","year":"1999","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"El-Belely, E.F., Farag, M.M.S., Said, H.A., Amin, A.S., Azab, E., Gobouri, A.A., and Fouda, A. (2021). Green Synthesis of Zinc Oxide Nanoparticles (ZnO-NPs) Using Arthrospira platensis (Class: Cyanophyceae) and Evaluation of their Biomedical Activities. Nanomaterials, 11.","DOI":"10.3390\/nano11010095"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1021\/np100422z","article-title":"Absolute Configuration of (\u2212)-Gambogic Acid, an Antitumor Agent","volume":"74","author":"Ren","year":"2011","journal-title":"J. Nat. Prod."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8617290","DOI":"10.1155\/2021\/8617290","article-title":"Synthesis of Zinc Oxide Nanoparticles by Hydrothermal Methods and Spectroscopic Investigation of Ultraviolet Radiation Protective Properties","volume":"2021","author":"Bulcha","year":"2021","journal-title":"J. Nanomater."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4533","DOI":"10.1002\/slct.202100358","article-title":"Characterization Study of Cytotoxicity of Green Synthesized ZnO Nanoparticles Loaded with Anti-Cancer Doxorubicin Drug","volume":"6","author":"Gomathi","year":"2021","journal-title":"ChemistrySelect"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/1475-2867-13-89","article-title":"Acidic extracellular microenvironment and cancer","volume":"13","author":"Kato","year":"2013","journal-title":"Cancer Cell Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1146\/annurev-physiol-021119-034627","article-title":"The Acidic Tumor Microenvironment as a Driver of Cancer","volume":"82","author":"Boedtkjer","year":"2020","journal-title":"Annu. Rev. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1007\/s12011-023-03803-z","article-title":"Zinc Oxide Nanoparticles and Cancer Chemotherapy: Helpful Tools for Enhancing Chemo-sensitivity and Reducing Side Effects?","volume":"202","author":"Mohammadi","year":"2024","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.lfs.2016.08.009","article-title":"Solid Ehrlich carcinoma reproduces functional and biological characteristics of cancer cachexia","volume":"162","author":"Frajacomo","year":"2016","journal-title":"Life Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e12585","DOI":"10.1111\/jpi.12585","article-title":"Ameliorative effects of melatonin against solid Ehrlich carcinoma progression in female mice","volume":"67","author":"Amin","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e10608","DOI":"10.1016\/j.heliyon.2022.e10608","article-title":"Cisplatin for cancer therapy and overcoming chemoresistance","volume":"8","author":"Ranasinghe","year":"2022","journal-title":"Heliyon"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1007\/s10787-023-01346-2","article-title":"Using aspirin to prevent and treat cancer","volume":"32","author":"Lichtenberger","year":"2024","journal-title":"Inflammopharmacology"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Khan, P., Bhattacharya, A., Sengupta, D., Banerjee, S., Adhikary, A., and Das, T. (2019). Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-53134-0"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1182\/blood.2019004017","article-title":"How I treat cancer-associated anemia","volume":"136","author":"Gilreath","year":"2020","journal-title":"Blood"},{"key":"ref_58","first-page":"1223","article-title":"Prognostic impact of haemoglobin levels in breast cancer","volume":"27","author":"Boehm","year":"2007","journal-title":"Anticancer Res."},{"key":"ref_59","first-page":"3418975","article-title":"Role of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Cancer Prevention and Cancer Promotion","volume":"2019","author":"Wong","year":"2019","journal-title":"Adv. Pharmacol. Pharm. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Weng, M., Zhao, W., Yue, Y., Guo, M., Nan, K., Liao, Q., Sun, M., Zhou, D., and Miao, C. (2022). High preoperative white blood cell count determines poor prognosis and is associated with an immunosuppressive microenvironment in colorectal cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.943423"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Chen, S.-L., Xue, N., Wu, M.-T., Chen, H., He, X., Li, J.-P., Liu, W.-L., and Dai, S.-Q. (2016). Influence of Preoperative Serum Aspartate Aminotransferase (AST) Level on the Prognosis of Patients with Non-Small Cell Lung Cancer. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17091474"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e24356","DOI":"10.1002\/jcla.24356","article-title":"Elevated AST\/ALT ratio is associated with all-cause mortality and cancer incident","volume":"36","author":"Chen","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wang, M., Liu, C., Hao, M., Wang, W., Li, Y., Shi, J., Zhang, X., and Dang, S. (2023). Hepatoprotective effects of aspirin on diethylnitrosamine-induced hepatocellular carcinoma in rats by reducing inflammation levels and PD-L1 expression. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-48812-z"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sedky, N.K., Abdel-Kader, N.M., Issa, M.Y., Abdelhady, M.M.M., Shamma, S.N., Bakowsky, U., and Fahmy, S.A. (2023). Co-Delivery of Ylang Ylang Oil of Cananga odorata and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24098392"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/22\/5327\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:30:51Z","timestamp":1760113851000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/22\/5327"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,12]]},"references-count":64,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["molecules29225327"],"URL":"https:\/\/doi.org\/10.3390\/molecules29225327","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,12]]}}}