PSMA 靶向还原裂解超支化聚酰胺-胺基因传递系统治疗前列腺癌骨转移。

PSMA-Targeting Reduction-Cleavable Hyperbranched Polyamide-Amine Gene Delivery System to Treat the Bone Metastases of Prostate Cancer.

机构信息

Department of Orthopedic Surgery, Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangzhou, Guangdong Province 510080, People's Republic of China.

Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, People's Republic of China.

出版信息

Int J Nanomedicine. 2020 Sep 28;15:7173-7184. doi: 10.2147/IJN.S268398. eCollection 2020.

OBJECTIVE

This study aimed to develop aptamer-anchored hyperbranched poly(amido amine) (HPAA) for the systemic delivery of and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro.

METHODS

A glutathione (GSH)-responsive cationic HPAA was prepared by the Michael addition reaction. Furthermore, HPAA-PEG was produced by PEGylation, and then the aptamer targeted to prostate-specific membrane antigen (PSMA) was conjugated to the HPAA-PEG. The obtained HPAA-PEG-APT could form nanocomplexes with through electrostatic adsorption.

RESULTS

The results of immunocytochemistry indicated that the complexes could target PSMA-expressing LNCaP cells. The ability of HPAA-PEG-APT to facilitate the delivery of into LNCaP cells was proven, and HPAA-PEG-APT/ demonstrated enhanced antitumor activity, lower cytotoxicity and better biocompatibility in vitro. Moreover, in a tibial injection tumor model, the intravenous injection of the HPAA-PEG-APT/ complex significantly inhibited cancer growth and extended the survival time.

CONCLUSION

This study provided an aptamer-anchored HPAA-loaded gene system to deliver for better therapeutic efficacy of bone metastasis of prostate cancer.

目的

本研究旨在开发适体锚定的超支化聚（酰胺-胺）（HPAA）用于系统递送，并评估其在体内和体外治疗前列腺癌骨转移的潜力。

方法

通过迈克尔加成反应制备谷胱甘肽（GSH）响应性阳离子 HPAA。此外，通过 PEGylation 制备 HPAA-PEG，然后将针对前列腺特异性膜抗原（PSMA）的适体连接到 HPAA-PEG 上。所得的 HPAA-PEG-APT 可通过静电吸附与形成纳米复合物。

结果

免疫细胞化学结果表明，该复合物可以靶向表达 PSMA 的 LNCaP 细胞。证明了 HPAA-PEG-APT 能够促进将递送至 LNCaP 细胞，并且 HPAA-PEG-APT/显示出增强的抗肿瘤活性、更低的细胞毒性和更好的体外生物相容性。此外，在胫骨注射肿瘤模型中，静脉注射 HPAA-PEG-APT/ 复合物显著抑制了肿瘤生长并延长了存活时间。