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.

中文翻译：

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PSMA靶向黑色素样纳米颗粒作为前列腺癌治疗学的多功能纳米平台

前列腺特异性膜抗原（PSMA）在大多数前列腺肿瘤细胞的表面上高度表达，被认为是前列腺癌成像和治疗的有希望的靶标。可以建立靶向PSMA的治疗诊断探针，以实现对该癌症类型的早期诊断和治疗。在这项贡献中，我们制备了装饰有小分子PSMA抑制剂N- [ N -[（S）-1,3-二羧丙基]氨基甲酰基]-（S的多功能黑色素样聚多巴胺（PDA）纳米载体-l-赖氨酸（DCL）。然后用全氟戊烷（PFP）对PDA-DCL进行功能化，并装载光敏剂二氢卟酚e6（Ce6），得到Ce6 @ PDA-DCL-PFP，该产品成功用于超声引导下的光动力/光热疗法联合治疗前列腺癌。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）和在体内更多的肿瘤蓄积（4.6倍），表明具有强大的主动靶向能力。同时，这种新的纳米平台显着增强了体内肿瘤部位的超声对比信号，从而有助于精确，实时地检测肿瘤。此外，这种负载Ce6的PDA纳米平台在660 nm和808 nm辐射下产生了PDT和PTT的协同作用，与体外和体内的单个疗法相比，诱导了更有效的杀伤作用。此外，在相同的照射条件下，目标组的肿瘤比非目标组的肿瘤更有效地被抑制。这种多功能的探针可能对前列腺癌的精确和早期治疗有很大的潜力。