文獻名：PSMA-targeted melanin-like nanoparticles as a multifunctional nanoplatform for prostate cancer theranostics

作者： Liqun Dai^a  Guohua Shen^a  Yuanyuan Wang^b  Peng Yang^c  Hong Wang^d  and  Zhenhua Liu ^e   

^a Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China

^b Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China

^c College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, People's Republic of China

^d Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, People's Republic of China

^e Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, People's Republic of China

摘要：Prostate-specific membrane antigen (PSMA) is highly expressed on the surface of most prostate tumor cells and is considered a promising target for prostate cancer imaging and treatment. It is possible to establish a PSMA-targeted theranostic probe to achieve early diagnosis and treatment of this cancer type. In this contribution, we prepared a multifunctional melanin-like polydopamine (PDA) nanocarrier decorated with a small-molecule PSMA inhibitor, N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-(S)-l-lysine (DCL). PDA-DCL was then functionalized with perfluoropentane (PFP) and loaded with the photosensitizer chlorin e6 (Ce6) to give Ce6@PDA-DCL-PFP, which was successfully used for ultrasound-guided combined photodynamic/photothermal therapy (PDT/PTT) of prostate cancer. Compared with the corresponding non-targeted probe (Ce6@PDA-PEG-PFP), our targeted probe induced higher cellular uptake in vitro (6.5-fold) and more tumor accumulation in vivo (4.6-fold), suggesting strong active targeting capacity. Meanwhile, this new nanoplatform significantly enhanced the ultrasound contrast signal at the tumor site in vivo, thus facilitating precise and real-time detection of the tumor. In addition, this Ce6-loaded PDA nanoplatform produced a synergistic effect of PDT and PTT under 660 nm and 808 nm irradiation, inducing a more efficient killing effect compared with the individual therapy in vitro and in vivo. Furthermore, the tumor in the targeted group was more effectively suppressed than that in the non-targeted group under the same irradiation condition. This multifunctional probe may hold great potential for precise and early theranostics of prostate cancer.

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