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Dual\u2010targeted inhibitors of phosphoinositide 3\u2010kinase (PI3\u2010K) and histone deacetylase (HDAC) have emerged as promising cancer therapy candidates. However, poor aqueous solubility and bioavailability limited their efficacy in cancer. The present study investigates the encapsulation of a PI3\u2010K\u03b4\/HDAC6 dual inhibitor into hybrid block copolymers (polylactic acid\u2010methoxy polyethylene glycol; polylactic acid\u2010polyethylene glycol\u2010polypropylene glycol\u2010polyethylene glycol\u2010polylactic acid) (HSB\u2010510) as a delivery system to target PI3\u2010K\u03b4 and HDAC6 pathways in breast cancer cells. The prepared HSB\u2010510 showed an average diameter of 96\u2009\u00b1\u20093\u2009nm, a zeta potential of \u221217\u2009\u00b1\u20092\u2009mV, and PDI of \u02c20.1 with a slow and sustained release profile of PI3\u2010K\u03b4\/HDAC6 inhibitors in a nonphysiological buffer. In vitro studies with HSB\u2010510 have demonstrated substantial growth inhibition of breast cancer cell lines, MDA\u2010MB\u2010468, SUM\u2010149, MCF\u20107, and Ehrlich ascites carcinoma (EAC)\u00a0as well as downregulation of phospho\u2010AKT, phospho\u2010ERK, and c\u2010Myc levels. Importantly, bi\u2010weekly treatment of Balb\/c wild\u2010type mice harboring EAC cells with HSB\u2010510 at a dose of 25\u2009mg\/kg resulted in significant tumor growth inhibition. The treatment with HSB\u2010510 was without any significant effect on the body weights of the mice. These results demonstrate that a novel Quatramer encapsulation of a PI3\u2010K\u03b4\/HDAC6 dual inhibitor (HSB\u2010510) represents an approach for the successful targeting of breast cancer and potentially other cancer types.<\/jats:p>","DOI":"10.1002\/btm2.10541","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T08:37:48Z","timestamp":1683880668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>Quatramer\u2122<\/scp>\n                    encapsulation of dual\u2010targeted\n                    <scp>PI3\u2010K\u03b4<\/scp>\n                    \/\n                    <scp>HDAC6<\/scp>\n                    inhibitor,\n                    <scp>HSB<\/scp>\n                    \u2010510, suppresses growth of breast 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