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• W2113238094 abstract "Abstract Brain (central nervous system; CNS) metastases pose a life-threatening problem for women with advanced metastatic breast cancer. It has recently been shown that the vasculature within preclinical brain metastasis model markedly restricts paclitaxel delivery in approximately 90% of CNS lesions. Therefore to improve efficacy, we have developed an ultra-small hyaluronic acid (HA) paclitaxel nanoconjugate (∼5 kDa) that can passively diffuse across the leaky blood–tumor barrier and then be taken up into cancer cells (MDA–MB–231Br) via CD44 receptor–mediated endocytocis. Using CD44 receptor–mediated endocytosis as an uptake mechanism, HA-paclitaxel was able to bypass p-glycoprotein–mediated efflux on the surface of the cancer cells. In vitro cytoxicity of the conjugate and free paclitaxel were similar in that they (i) both caused cell-cycle arrest in the G2–M phase, (ii) showed similar degrees of apoptosis induction (cleaved caspase), and (iii) had similar IC50 values when compared with paclitaxel in MTT assay. A preclinical model of brain metastases of breast cancer using intracardiac injections of Luc-2 transfected MDA–MB–231Br cells was used to evaluate in vivo efficacy of the nanoconjugate. The animals administered with HA–paclitaxel nanoconjugate had significantly longer overall survival compared with the control and the paclitaxel-treated group (P &lt; 0.05). This study suggests that the small molecular weight HA–paclitaxel nanoconjugates can improve standard chemotherapeutic drug efficacy in a preclinical model of brain metastases of breast cancer. Mol Cancer Ther; 12(11); 2389–99. ©2013 AACR." @default.
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• W2113238094 date "2013-11-01" @default.
• W2113238094 modified "2023-10-16" @default.
• W2113238094 title "Paclitaxel–Hyaluronic NanoConjugates Prolong Overall Survival in a Preclinical Brain Metastases of Breast Cancer Model" @default.
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• W2113238094 doi "https://doi.org/10.1158/1535-7163.mct-13-0132" @default.
• W2113238094 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8391070" @default.
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