Polylactide-tethered prodrugs in polymeric nanoparticles as reliable nanomedicines for the efficient eradication of patient-derived hepatocellular carcinoma.
Polylactide-tethered prodrugs in polymeric nanoparticles as reliable nanomedicines for the efficient eradication of patient-derived hepatocellular carcinoma.
复制标题
聚合物纳米粒子中的聚丙交酯系前药作为可靠的纳米药物，可有效根除患者源性肝细胞癌
DOI：
10.7150/thno.26161
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发表时间：
2018
期刊：
影响因子：
12.4
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Wang H;Zhou L;Xie K;Wu J;Song P;Xie H;Zhou L;Liu J;Xu X;Shen Y;Zheng S
Nanomedicines have been extensively explored for cancer treatment, and their efficacies have arguably been proven in various cancer cell-derived xenograft (CDX) mouse models. However, they generally fail to show such therapeutic advantages in patients because of the huge pathological differences between human tumors and CDX models. Methods: In this study, we fabricated colloidal ultrastable nanomedicines from polymeric prodrugs and compared the therapeutic efficacies in hepatocellular carcinoma (HCC) CDX and clinically relevant patient-derived xenograft (PDX) mouse models, which closely mimic human tumor pathological properties. Working towards this goal, we esterified a highly potent SN38 (7-ethyl-10-hydroxycamptothecin) agent using oligo- or polylactide (oLA or PLA) segments with varying molecular weights. Results: The resulting SN38 conjugates assembled with polyethylene glycol-block-polylactic acid to form systemically injectable nanomedicines. With increasing PLA chain length, the SN38 conjugates showed extended retention in the nanoparticles and superior antitumor activity, completely eradicating xenografted tumors in both mouse models. Our data implicate that these small-sized and ultrastable nanomedicines might also efficaciously treat cancer in patients. More interestingly, the systemically delivered nanomedicines notably alleviated the incidence of bloody diarrhea. Conclusion: Our studies demonstrate that the appropriate molecular editing of anticancer drugs enables the generation of better tolerated cytotoxic nanotherapy for cancer, which represents a potentially useful scaffold for further clinical translation.
