National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Jilin Collaborative Innovation Center for Antibody Engineering, Jilin Medical University, Jilin, China.
Int J Cancer. 2024 Dec 1;155(11):2094-2106. doi: 10.1002/ijc.35065. Epub 2024 Jul 10.
The precise delivery of drugs to tumor sites and the thermoresistance of tumors remain major challenges in photothermal therapy (PTT). Somatostatin receptor 2 (SSTR2) is proposed as an ideal target for the precise treatment of SCLC. We developed a targeting nano-drug delivery system comprising anti-SSTR2 monoclonal antibody (MAb) surface-modified nanoparticles co-encapsulating Cypate and gambogic acid (GA). The formed SGCPNs demonstrated excellent monodispersity, physiological stability, preferable biocompatibility, and resultant efficient photothermal conversion efficacy. SGCPNs were quickly internalized by SSTR2-overexpressing SCLC cells, triggering the release of GA under acidic and near-infrared (NIR) laser irradiation environments, leading to their escape from lysosomes to the cytosol and then diffusion into the nucleus. SGCPNs can not only decrease the cell survival rate but also inhibit the activity of heat shock protein 90 (HSP90). SGCPNs can be precisely delivered to xenograft tumors of SSTR2-positive SCLC in vivo. Upon NIR laser irradiation, therapy of SGCPNs showed significant tumor regression. In conclusion, SGCPNs provide a new chemo-photothermal synergistic treatment strategy for targeting SCLC.
药物精确递送到肿瘤部位和肿瘤的热抗性仍然是光热治疗（PTT）的主要挑战。生长抑素受体 2（SSTR2）被提议作为精确治疗 SCLC 的理想靶点。我们开发了一种靶向纳米药物递送系统，包括抗 SSTR2 单克隆抗体（MAb）表面修饰的纳米颗粒，共包封了 Cypate 和藤黄酸（GA）。形成的 SGCPNs 表现出优异的单分散性、生理稳定性、良好的生物相容性和高效的光热转换效率。SGCPNs 被 SSTR2 过表达的 SCLC 细胞快速内化，在酸性和近红外（NIR）激光照射环境下触发 GA 的释放，导致它们从溶酶体逃逸到细胞质，然后扩散到核内。SGCPNs 不仅可以降低细胞存活率，还可以抑制热休克蛋白 90（HSP90）的活性。SGCPNs 可以精确递送到体内 SSTR2 阳性 SCLC 的异种移植肿瘤。在 NIR 激光照射下，SGCPNs 的治疗显示出显著的肿瘤消退。总之，SGCPNs 为靶向 SCLC 提供了一种新的化疗-光热协同治疗策略。
