Cisplatin Prodrug-Loaded Nanoparticles Based on Physalis Mottle Virus for Cancer Therapy.
Cisplatin Prodrug-Loaded Nanoparticles Based on Physalis Mottle Virus for Cancer Therapy.
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DOI：
10.1021/acs.molpharmaceut.0c00834
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发表时间：
2020-12-07
影响因子：
4.9
通讯作者：
Steinmetz NF
中科院分区：
文献类型：
--
作者：
Hu H;Steinmetz NF
Nanoparticle-based prodrugs offer an effective strategy to improve the safety and delivery of small-molecule therapeutics while reducing the risk of drug resistance. Here, we conjugated a maleimide-functionalized cisplatin prodrug containing Pt(IV) to the internal and/or external surface of virus-like particles (VLPs) derived from Physalis mottle virus (PhMV) to develop a pH-sensitive drug delivery system. The internally loaded and PEGylated VLPs (Pt-PhMVCy5.5-PEG) were taken up efficiently by cancer cells where they released platinum, presumably as a reduced, DNA-reactive Pt(II) complex, rapidly under acidic conditions in vitro (>80% in 30 h). The efficacy of the VLP-based drug delivery system was demonstrated against a panel of cancer cell lines, including cell lines resistant to platinum therapy. Furthermore, Pt-PhMVCy5.5-PEG successfully inhibited the growth of xenograft MDA-MB-231 breast tumors in vivo and significantly prolonged the survival of mice compared to free cisplatin and cisplatin-maleimide. Pt-PhMVCy5.5-PEG therefore appears promising as a prodrug to overcome the limitations of conventional platinum-based drugs for cancer therapy.
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影响因子：
4.9
作者：
Franke, Christina E.;Czapar, Anna E.;Steinmetz, Nicole F.
通讯作者：
Steinmetz, Nicole F.
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通讯作者：
Steinmetz NF
影响因子：
9.5
作者：
Hu, He;Masarapu, Hema;Steinmetz, Nicole F.
通讯作者：
Steinmetz, Nicole F.