Lee Chung-Sung, Na Kun
Department of Biotechnology, The Catholic University of Korea , 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Korea.
Biomacromolecules. 2014 Nov 10;15(11):4228-38. doi: 10.1021/bm501258s. Epub 2014 Oct 7.
A photochemically triggered cytosolic drug delivery system based on combining tumor-targeting pH-responsive hyaluronic acid (HA) nanoparticles (PHANs) with anticancer therapeutics (doxorubicin; DOX) was successfully developed for light-induced cancer therapy. PHANs were prepared through the self-assembly of a photosensitizer (PS), chlorin e6, and a pH-responsive moiety, poly(diisopropylaminoethyl) aspartamide (PDIPASP),conjugated to HA. DOX encapsulating PHANs (DOX@PHANs) have a uniform spherical shape,a sub-100 nm size distribution and a negative surface charge. The pH-responsiveness of PHANs leads to their disassembly due to the protonation of PDIPASP, which triggers DOX release. Competitive cellular uptake and confocal microscopy studies revealed CD44 receptor-mediated endocytosis, endosomal escape capability and efficient drug targeting. Compared to treatment with free DOX or PHANs, the combined treatment with DOX@PHANs and spatiotemporally defined irradiation remarkably improved the anticancer efficacy both in vitro and in vivo studies. Therefore, this strategy shows promise for the photochemically triggered cytosolic drug delivery of therapeutic agents for light-induced cancer therapy.
通过将肿瘤靶向性pH响应性透明质酸（HA）纳米颗粒（PHANs）与抗癌治疗药物（阿霉素；DOX）相结合，成功开发了一种基于光化学触发的胞质药物递送系统，用于光诱导癌症治疗。PHANs是通过将光敏剂（PS）二氢卟吩e6与pH响应部分聚（二异丙基氨基乙基）天冬酰胺（PDIPASP）共轭到HA上进行自组装制备的。包裹DOX的PHANs（DOX@PHANs）具有均匀的球形形状、小于100nm的尺寸分布和负表面电荷。PHANs的pH响应性导致其由于PDIPASP的质子化而解体，从而触发DOX释放。竞争性细胞摄取和共聚焦显微镜研究揭示了CD44受体介导的内吞作用、内体逃逸能力和有效的药物靶向性。与游离DOX或PHANs治疗相比，DOX@PHANs与时空定义照射的联合治疗在体外和体内研究中均显著提高了抗癌疗效。因此，该策略在光诱导癌症治疗中用于光化学触发的治疗剂胞质药物递送方面显示出前景。
