Imaging-guided photo-therapeutic nanoporphyrin synergized HSP90 inhibitor in patient-derived xenograft bladder cancer model

Photodynamic therapy is a promising and effective non-invasive therapeutic approach for the treatment of bladder cancers. Therapies targeting HSP90 have the advantage of tumor cell selectivity and have shown great preclinical efficacy. In this study, we evaluated a novel multifunctional nanoporphyrin platform loaded with an HSP90 inhibitor 17AAG (NP-AAG) for use as a multi-modality therapy against bladder cancer. NP-AAG was efficiently accumulated and retained at bladder cancer patient-derived xenograft (PDX) over 7 days. PDX tumors could be synergistically eradicated with a single intravenous injection of NP-AAG followed by multiple light treatments within 7 days. NP-AAG mediated treatment could not only specifically deliver 17AAG and produce heat and reactive oxygen species, but also more effectively inhibit essential bladder cancer essential signaling molecules like Akt, Src, and Erk, as well as HIF-1α induced by photo-therapy. This multifunctional nanoplatform has high clinical relevance and could dramatically improve management for bladder cancers with minimal toxicity.

Nanomedicine : nanotechnology, biology, and medicine. 2018 Jan 06 [Epub ahead of print]

Qilai Long, Tzu-Yin Lin, Yee Huang, Xiaocen Li, Ai-Hong Ma, Hongyong Zhang, Randy Carney, Susan Airhart, Kit S Lam, Chong-Xian Pan, Yuanpei Li

Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China; Department of Internal Medicine, University of California Davis, Sacramento, CA, USA., Department of Internal Medicine, University of California Davis, Sacramento, CA, USA., Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, USA; Institute of Animal Husbandry and Veterinary Science, Zhejiang Academy of Agricultural Sciences., Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, USA., The Jackson Laboratory, Bar Harbor, Maine, USA., Department of Internal Medicine, University of California Davis, Sacramento, CA, USA; Department of Urology, University of California Davis, Sacramento, CA, USA; VA Northern California Health Care System, Mather, CA. Electronic address: ., Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, USA. Electronic address: .

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