title: HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy.
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.
authors.affiliation: 1. Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA 95817, USA;
authors.forename: Tzu-Yin
authors.initials: TY
authors.lastname: Lin
authors.affiliation: 2. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA;
authors.forename: Wenchang
authors.initials: W
authors.lastname: Guo
authors.affiliation: 3. Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China;
authors.forename: Qilai
authors.initials: Q
authors.lastname: Long
authors.affiliation: 4. Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA;
authors.forename: Aihong
authors.initials: A
authors.lastname: Ma
authors.affiliation: 4. Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA;
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: 1. Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA 95817, USA;
authors.forename: Hongyong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 4. Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA;
authors.forename: Yee
authors.initials: Y
authors.lastname: Huang
authors.affiliation: 4. Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA;
authors.forename: Siddarth
authors.initials: S
authors.lastname: Chandrasekaran
authors.affiliation: 1. Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA 95817, USA;; 5. VA Northern California Health Care System, Mather, CA, USA.
authors.forename: Chongxian
authors.initials: C
authors.lastname: Pan
authors.affiliation: 1. Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA 95817, USA;; 4. Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA;
authors.forename: Kit S
authors.initials: KS
authors.lastname: Lam
authors.affiliation: 4. Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA;
authors.forename: Yuanpei
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D064593:Heterografts; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000628:therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000068936:Theranostic Nanomedicine / Q000379:methods; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D018841:HSP90 Heat-Shock Proteins; D011166:Porphyrins; D017382:Reactive Oxygen Species
keywords: Combination therapy; Hsp90 inhibitor; Nano-theranostics; Photo-therapy; Prostate cancer.