Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
J Mater Chem B. 2021 Jan 28;9(4):1151-1161. doi: 10.1039/d0tb02576c. Epub 2021 Jan 12.
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.
前列腺特异性膜抗原（PSMA）在大多数前列腺肿瘤细胞表面高度表达，被认为是前列腺癌成像和治疗的有前途的靶点。有可能建立一种 PSMA 靶向治疗探针，以实现对这种癌症类型的早期诊断和治疗。在本研究中，我们制备了一种多功能黑色素样聚多巴胺（PDA）纳米载体，该载体表面修饰有小分子 PSMA 抑制剂 N-[N-[(S)-1,3-二羧基丙基]氨基甲酰基]-(S)-L-赖氨酸（DCL）。然后，PDA-DCL 用全氟戊烷（PFP）功能化，并负载光敏剂氯[e6]（Ce6），得到 Ce6@PDA-DCL-PFP，该探针成功地用于超声引导的联合光动力/光热治疗（PDT/PTT）前列腺癌。与相应的非靶向探针（Ce6@PDA-PEG-PFP）相比，我们的靶向探针在体外诱导更高的细胞摄取（6.5 倍）和体内更多的肿瘤积累（4.6 倍），表明具有很强的主动靶向能力。同时，这种新的纳米平台显著增强了体内肿瘤部位的超声对比信号，从而便于对肿瘤进行精确和实时的检测。此外，负载 Ce6 的 PDA 纳米平台在 660nm 和 808nm 照射下产生光动力和光热治疗的协同效应，与体外和体内的单一疗法相比，诱导出更有效的杀伤效果。此外，在相同的照射条件下，靶向组的肿瘤比非靶向组更有效地被抑制。这种多功能探针可能在前列腺癌的精确和早期治疗中有很大的潜力。
