{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T16:05:05Z","timestamp":1784909105919,"version":"3.55.0"},"reference-count":53,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T00:00:00Z","timestamp":1654128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Qatar University Student Grant","award":["QUST-2-CHS-2020-11"],"award-info":[{"award-number":["QUST-2-CHS-2020-11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Tyrosine kinase inhibitors (TKIs) are the new generation of anti-cancer drugs with high potential against cancer cells\u2019 proliferation and growth. However, TKIs are associated with severe cardiotoxicity, limiting their clinical value. One TKI that has been developed recently but not explored much is Ponatinib. The use of nanoparticles (NPs) as a better therapeutic agent to deliver anti-cancer drugs and reduce their cardiotoxicity has been recently considered. In this study, with the aim to reduce Ponatinib cardiotoxicity, Poly(D,L-lactide-co-glycolide)-b-poly(ethyleneoxide)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was used to synthesize Ponatinib in loaded PLGA-PEG-PLGA NPs for chronic myeloid leukemia (CML) treatment. In addition to physicochemical NPs characterization (NPs shape, size, size distribution, surface charge, dissolution rate, drug content, and efficacy of encapsulation) the efficacy and safety of these drug-delivery systems were assessed in vivo using zebrafish. Zebrafish are a powerful animal model for investigating the cardiotoxicity associated with anti-cancer drugs such as TKIs, to determine the optimum concentration of smart NPs with the least side effects, and to generate a xenograft model of several cancer types. Therefore, the cardiotoxicity of unloaded and drug-loaded PLGA-PEG-PLGA NPs was studied using the zebrafish model by measuring the survival rate and cardiac function parameters, and therapeutic concentration for in vivo efficacy studies was optimized in an in vivo setting. Further, the efficacy of drug-loaded PLGA-PEG-PLGA NPs was tested on the zebrafish cancer xenograft model, in which human myelogenous leukemia cell line K562 was transplanted into zebrafish embryos. Our results demonstrated that the Ponatinib-loaded PLGA-PEG-PLGA NPs at a concentration of 0.001 mg\/mL are non-toxic\/non-cardio-toxic in the studied zebrafish xenograft model.<\/jats:p>","DOI":"10.3390\/ma15113960","type":"journal-article","created":{"date-parts":[[2022,6,2]],"date-time":"2022-06-02T04:46:23Z","timestamp":1654145183000},"page":"3960","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Reduced Cardiotoxicity of Ponatinib-Loaded PLGA-PEG-PLGA Nanoparticles in Zebrafish Xenograft Model"],"prefix":"10.3390","volume":"15","author":[{"given":"Hissa F.","family":"Al-Thani","sequence":"first","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"},{"name":"Department of Biomedical Science, College of Health Sciences, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar","family":"Shurbaji","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9656-8367","authenticated-orcid":false,"given":"Zain Zaki","family":"Zakaria","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maram H.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8101-6359","authenticated-orcid":false,"given":"Katerina","family":"Goracinova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"},{"name":"Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Mother Theresa 47, 1000 Skopje, North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5745-9643","authenticated-orcid":false,"given":"Hesham M.","family":"Korashy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3825-9934","authenticated-orcid":false,"given":"Huseyin C.","family":"Yalcin","sequence":"additional","affiliation":[{"name":"Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"448","DOI":"10.21037\/jtd.2017.02.75","article-title":"Cancer prevention from the perspective of global cancer burden patterns","volume":"9","author":"Nagai","year":"2017","journal-title":"J. Thorac. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21087","DOI":"10.3390\/ijms141021087","article-title":"Cancer development, progression, and therapy: An epigenetic overview","volume":"14","author":"Sarkar","year":"2013","journal-title":"Int. J. Mol. 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