酶促PEG-聚（胺<i>共</i>-二硫化物酯）纳米微粒作为pH-和氧化还原响应性药物纳米载体为有效的抗肿瘤治疗,ACS Applied Materials & Interfaces

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酶促PEG-聚（胺共-二硫化物酯）纳米微粒作为pH-和氧化还原响应性药物纳米载体为有效的抗肿瘤治疗
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2017-09-01 00:00:00 , DOI: 10.1021/acsami.7b10148
Ya Chen ₁ , Meifei Su ₁ , Yingqin Li ₁ , Jinbiao Gao ₁ , Chao Zhang ₁ , Zhong Cao ₁ , Jiangbing Zhou ₂ , Jie Liu ₁ , Zhaozhong Jiang ₃

Affiliation

我们已经设计和构建了新颖的多功能纳米颗粒药物递送系统，该系统在生理条件下稳定并且对肿瘤相关的pH和细胞内还原电位有反应。将纳米颗粒从酶促合成聚（乙二醇）（PEG） -聚（ω-pentadecalactone-制造共- ñ -methyldiethyleneamine- CO（PEG-PPMD）和PEG-聚（ε -己内酯-3,3'- dithiodipropionate） -共- ñ -methyldiethyleneamine-共经由自组装-3,3'- dithiodipropionate）（PEG-PCMD）嵌段共聚物在水溶液中的处理。在酸性pH值和还原剂（例如d，l-二硫苏糖醇或谷胱甘肽），由于氨基的质子化和胶束核心中的二硫键还原性裂解，纳米级胶束颗粒迅速膨胀并崩解。一致地，多西他赛（DTX）加载的PEG-PPMD和PEG-PCMD胶束可通过酸性内体pH值和高细胞内还原潜能协同触发，从而迅速释放药物以有效杀死癌细胞。基于PEG-PPMD和PEG-PCMD共聚物的药物制剂在抑制小鼠肿瘤生长方面表现出比游离DTX显着更高的效力，而它们对重要器官组织的治疗作用则微乎其微。这些结果表明，PEG-PPMD和PEG-PCMD纳米粒子具有巨大的潜力，可以用作针对特定部位的受控药物递送载体，以进行安全有效的抗肿瘤治疗。

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Enzymatic PEG-Poly(amine-co-disulfide ester) Nanoparticles as pH- and Redox-Responsive Drug Nanocarriers for Efficient Antitumor Treatment

We have designed and constructed novel multifunctional nanoparticle drug-delivery systems that are stable under physiological conditions and responsive to tumor-relevant pH and intracellular reduction potential. The nanoparticles were fabricated from enzymatically synthesized poly(ethylene glycol) (PEG)-poly(ω-pentadecalactone-co-N-methyldiethyleneamine-co-3,3′-dithiodipropionate) (PEG-PPMD) and PEG-poly(ε-caprolactone-co-N-methyldiethyleneamine-co-3,3′-dithiodipropionate) (PEG-PCMD) block copolymers via self-assembly processes in aqueous solution. At acidic pH and in the presence of a reductant (e.g., d,l-dithiothreitol or glutathione), the nanosized micelle particles rapidly swell and disintegrate due to the protonation of amino groups and reductive cleavage of disulfide bonds in the micelle cores. Consistently, docetaxel (DTX)-loaded PEG-PPMD and PEG-PCMD micelles can be triggered synergistically by acidic endosomal pH and a high intracellular reduction potential to rapidly release the drug for efficient killing of cancer cells. The drug formulations based on PEG-PPMD and PEG-PCMD copolymers exhibited a substantially higher potency than free DTX in inhibiting tumor growth in mice, whereas their therapeutic effects on important organ tissues were minimal. These results demonstrate that PEG-PPMD and PEG-PCMD nanoparticles have a great potential to serve as site-specific, controlled drug-delivery vehicles for safe and efficient antitumor treatment.

更新日期：2017-09-04

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