Theranostics 2016; 6(9):1324-1335. doi:10.7150/thno.14882

Research Paper

HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy

Tzu-yin Lin1*, Wenchang Guo2*, Qilai Long3, Aihong Ma4, Qiangqiang Liu4, Hongyong Zhang1, Yee Huang4, Siddarth Chandrasekaran4, Chongxian Pan1,5, Kit S. Lam1, 4✉, Yuanpei Li4✉

1. Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA 95817, USA;
2. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA;
3. Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China;
4. Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA;
5. VA Northern California Health Care System, Mather, CA, USA.
*Authors contributed equally to this work.

Abstract

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.

Keywords: Nano-theranostics, Hsp90 inhibitor, Photo-therapy, Combination therapy, Prostate cancer.

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How to cite this article:
Lin Ty, Guo W, Long Q, Ma A, Liu Q, Zhang H, Huang Y, Chandrasekaran S, Pan C, Lam KS, Li Y. HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy. Theranostics 2016; 6(9):1324-1335. doi:10.7150/thno.14882. Available from http://www.thno.org/v06p1324.htm