HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy.
HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy.
复制标题
作者：
Lin TY;Guo W;Long Q;Ma A;Liu Q;Zhang H;Huang Y;Chandrasekaran S;Pan C;Lam KS;Li Y
光动力疗法（PDT）是一种有前途的非侵入性治疗方式，已被提出用于治疗前列腺癌，但该过程与有限的疗效、肿瘤复发和光毒性相关。在本研究中，我们提出开发一种新的多功能纳米平台，用于同时靶向递送热、活性氧（ROS）和热休克蛋白90（Hsp 90）抑制剂，用于前列腺癌的联合治疗。这个新的纳米平台结合了两个新开发的实体：1）独特的有机和生物相容的基于纳米卟啉的药物递送系统，其可以在肿瘤部位产生有效的热和ROS，同时具有光活化，用于双模式光热和光动力治疗（PTT/PDT），和2）新的Hsp 90抑制剂的纳米制剂，其可以降低由光疗诱导的促存活和血管生成信号分子的水平，因此，进一步使癌细胞对光疗敏感。此外，纳米颗粒具有可激活的近红外（NIR）荧光，用于光学成像，以方便地监测携带前列腺癌异种移植物的皮下和原位小鼠模型中的实时药物递送。这种新型多功能纳米平台具有很大的潜力，通过靶向联合治疗改善前列腺癌患者的护理。
Photodynamic therapy (PDT) is a promising non-invasive therapeutic modality that has been proposed for treating prostate cancer, but the procedure is associated with limited efficacy, tumor recurrence and photo-toxicity. In the present study, we proposed to develop a novel multifunctional nano-platform for targeted delivery of heat, reactive oxygen species (ROS) and heat shock protein 90 (Hsp90) inhibitor simultaneously for combination therapy against prostate cancer. This new nano-platform combines two newly developed entities: 1) a unique organic and biocompatible nanoporphyrin-based drug delivery system that can generate efficient heat and ROS simultaneously with light activation at the tumor sites for dual-modal photothermal- and photodynamic- therapy (PTT/PDT), and 2) new nano-formulations of Hsp90 inhibitors that can decrease the levels of pro-survival and angiogenic signaling molecules induced by phototherapy, therefore, further sensitizing cancer cells to phototherapy. Furthermore, the nanoparticles have activatable near infrared (NIR) fluorescence for optical imaging to conveniently monitor the real-time drug delivery in both subcutaneous and orthotopic mouse models bearing prostate cancer xenograft. This novel multifunctional nano-platform has great potential to improve the care of prostate cancer patients through targeted combination therapy.