Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology , Shanghai 200237, China.
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University , Shanghai 201620, China.
Biomacromolecules. 2017 Dec 11;18(12):3992-4001. doi: 10.1021/acs.biomac.7b01037. Epub 2017 Oct 31.
Drug resistance is a primary obstacle that seriously reduces the therapy efficiency of most chemotherapeutic agents. To address this issue, the photochemical internalization (PCI) was employed to help the anticancer drug escape from lysosome and improve their translocation to the nucleus. A pH-sensitive porphyrin-based amphiphilic block copolymer (PEG-b-PCL-a-porphyrin) was synthesized, which was acted not only as a carrier for the delivery of DOX but also as a photosensitizer for PCI. PEG-b-PCL-a-porphyrin as a drug carrier exhibited a higher drug loading capacity, entrapment efficiency, and DOX release content. The PCI effect of PEG-b-PCL-a-porphyrin was studied by confocal laser scanning microscopy, and the results showed that most of DOX could be translocated into the nucleus for DOX-loaded PEG-b-PCL-a-porphyrin micelles. Moreover, the IC of pH-sensitive DOX-loaded PEG-b-PCL-a-porphyrin micelles was much lower than that of its counterpart without pH-responsiveness, DOX-loaded PEG-b-PCL-porphyrin micelles. Therefore, this drug delivery system based on pH-sensitive porphyrin-containing block copolymer would act as a potential vehicle for overcoming drug resistance in chemotherapy.
耐药性是严重降低大多数化疗药物治疗效果的主要障碍。为了解决这个问题，采用光化学内化（PCI）帮助抗癌药物从溶酶体逃逸，并提高其向核内的转移。合成了一种 pH 敏感的基于卟啉的两亲嵌段共聚物（PEG-b-PCL-a-porphyrin），它不仅可以作为 DOX 的递送载体，还可以作为 PCI 的光敏剂。PEG-b-PCL-a-porphyrin 作为药物载体具有更高的载药量、包封效率和 DOX 释放含量。通过共聚焦激光扫描显微镜研究了 PEG-b-PCL-a-porphyrin 的 PCI 效应，结果表明，大多数 DOX 可以转移到细胞核中，用于负载 DOX 的 PEG-b-PCL-a-porphyrin 胶束。此外，pH 敏感的负载 DOX 的 PEG-b-PCL-a-porphyrin 胶束的 IC 远低于无 pH 响应性的对照物，负载 DOX 的 PEG-b-PCL-porphyrin 胶束。因此，基于 pH 敏感的含卟啉嵌段共聚物的药物传递系统将作为克服化疗耐药性的潜在载体。
