School of Chemistry and Chemical Engineering, Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin Key Laboratory of Drug Targeting and Bioimaging, Tianjin University of Technology, Tianjin 300384, China.
J Mater Chem B. 2020 Mar 11;8(10):2115-2122. doi: 10.1039/c9tb02890k.
Finding out how to overcome multistage biological barriers for nanocarriers in cancer therapy to obtain highly precise drug delivery is still a challenge. Herein, we prepared a multistage and cascaded switchable polymeric nanovehicle, self-assembled from polyethylene glycol grafted amphiphilic copolymer containing hydrophobic poly(ortho ester) and hydrophilic ethylenediamine-modified poly(glycidyl methacrylate) (PEG-g-p(GEDA-co-DMDEA)) for imaging-guided chemo-photothermal combination anticancer therapy. Notably, a novel ATRP initiator containing cyanine dye was designed and attached to the polymer, providing the nanovehicle with NIR-light induced photothermal and fluorescent properties. The PEG shell displayed tumor-microenvironment-induced detachment, resulting in the surface charge change of the nanovehicle from neutral to positive and thus enhancing cellular uptake. Subsequently, the hydrophobic pDMDEA hydrolyzed into a hydrophilic segment in the acidic lysosome, leading to sufficient drug release. Finally, with the aid of the photothermal property, the therapeutic drug DOX successfully escaped from the lysosome to exert chemotherapy. This well-defined polymeric nanoplatform promoted the development of designing novel theranostic polymeric nanovehicles for precise cancer therapy.
为了实现纳米载体在癌症治疗中高度精准的药物递送，克服多阶段生物屏障仍然是一个挑战。在此，我们制备了一种多阶段和级联可切换的聚合物纳米载体，它由聚乙二醇接枝的两亲性共聚物自组装而成，该共聚物含有疏水性聚（原酸酯）和亲水性乙二胺改性的聚（甲基丙烯酸缩水甘油酯）（PEG-g-p（GEDA-co-DMDEA）），用于成像引导的化学-光热联合抗癌治疗。值得注意的是，设计并连接了一种含有菁染料的新型 ATRP 引发剂，赋予纳米载体近红外光诱导的光热和荧光性能。PEG 壳层表现出肿瘤微环境诱导的脱落，导致纳米载体的表面电荷从中性变为正电荷，从而增强细胞摄取。随后，疏水性 pDMDEA 在酸性溶酶体中水解成亲水性片段，导致药物充分释放。最后，借助光热性能，治疗药物 DOX 成功地从溶酶体中逃脱，发挥化疗作用。这种明确的聚合物纳米平台促进了设计用于精确癌症治疗的新型治疗性聚合物纳米载体的发展。
