构建hPSMA单抗-聚多巴胺纳米粒子（PDA）@吲哚菁绿（ICG）复合荧光示踪剂及其对前列腺癌荧光靶标特性实验研究

根治性前列腺切除术（RP）和盆腔淋巴结清扫术（PLD）是局限性前列腺癌（PC）临床综合治疗中最重要的环节。合成特异性靶向PC组织、性质稳定的荧光示踪剂，用于术中精准判断、切除前列腺癌病灶和盆腔阳性淋巴结，对降低切缘阳性率、提高手术疗效和减少手术并发症具有重要意义。申请人前期已成功合成可高度特异性识别PC细胞的抗人PSMA胞外段单克隆抗体（anti-PSMA），并以组织相容性和生物安全性均较理想的聚多巴胺纳米粒子（PDA）为载体，成功构建PDA@ICG复合荧光示踪剂。本课题拟采用多学科技术与方法，进一步合成anti-PSMA-PDA@ICG作为前列腺癌特异性的复合示踪剂，检测其成分表征、结构表征、形貌表征和荧光特性，并采用自主研发的近红外成像系统，在体外、体内以及临床组织标本中验证其生物毒性、代谢特性、靶标特性和荧光特性，为其将来在临床实践中作为前列腺癌术中导航示踪剂提供理论依据和实验基础。

Radical prostatectomy with pelvic lymph node dissection plays a crucial role in the comprehensive treatment for localized prostate cancer. In the aim of reducing positive surgical margins and surgical complications, synthesis stable fluorescent tracer that specifically recognize prostate cancer cells may provide great assistance to accurate resection of cancer tissues and positive lymph nodes. In our previous study, we successfully synthesized anti-PSMA monoclonal antibodies that specifically recognized PSMA-expressing prostate cancer cells, and a fusion ICG tracer (PDA@ICG) with a polydopamine nanosphere backbone (PDA) that possesses ideal histocompatibility and biological safety. In this study, multidisciplinary techniques and methods will be used to further synthesize anti-PSMA-PDA@ICG as prostate cancer-specific fusion ICG tracer characterized in a componential, structural and morphological manner. The biological safety, metabolism characteristics, prostate cancer targeting and fluorescent properties will be further investigated in in vitro and in vivo settings as well as clinically acquired samples, by the near infrared imaging systems that we developed previously. This study will provide theoretical basis and experimental data to support the use of anti-PSMA-PDA@ICG fluorescent tracer as a tool of intraoperative navigation in prostate cancer surgeries.