Cheng Nuo, Zhou Qianqian, Jia Zongfang, Mu Yang, Zhang Sheng, Wang Lei, Chen Yunna
Anhui University of Chinese Medicine, Hefei, 230012, China.
MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei, 230012, China.
Mater Today Bio. 2025 Jan 1;30:101441. doi: 10.1016/j.mtbio.2024.101441. eCollection 2025 Feb.
The therapeutic effect of immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC) is unsatisfactory. The immune "cold" microenvironment caused by tumor-associated fibroblasts (TAFs) has an adverse effect on the antitumor response. Therefore, in this study, mixed cell membrane-coated porous magnetic nanoparticles (PMNPs) were constructed to deliver salvianolic acid B (SAB) to induce an antitumor immune response, facilitating the transition from a "cold" to a "hot" tumor and ultimately enhancing the therapeutic efficacy of immune checkpoint inhibitors. PMNP-SAB, which is based on a mixed coating of red blood cell membrane and TAF membrane (named PMNP-SAB@RTM), can simultaneously achieve the dual effects of "immune escape" and "homologous targeting". Under the influence of an external magnetic field (MF), SAB can be targeted and concentrated at the tumor site. The SAB released in tumors can effectively inhibit the production of extracellular matrix (ECM) by TAFs, promote T-cell infiltration, and induce antitumor immune responses. Ultimately, the combination of PMNP-SAB@RTM and BMS-1 (PD-1/PD-L1 inhibitor 1) effectively inhibited tumor growth. Finally, this study presents a precise and effective new strategy for TNBC immunotherapy on the basis of the differentiation of "cold" and "hot" microenvironments.
免疫检查点抑制剂（ICIs）在三阴性乳腺癌（TNBC）中的治疗效果并不理想。肿瘤相关成纤维细胞（TAFs）导致的免疫“冷”微环境对抗肿瘤反应产生不利影响。因此，在本研究中，构建了混合细胞膜包覆的多孔磁性纳米颗粒（PMNPs）来递送丹酚酸B（SAB）以诱导抗肿瘤免疫反应，促进从“冷”肿瘤向“热”肿瘤的转变，并最终提高免疫检查点抑制剂的治疗效果。基于红细胞膜和TAF膜的混合涂层的PMNP-SAB（命名为PMNP-SAB@RTM）能够同时实现“免疫逃逸”和“同源靶向”的双重效果。在外加磁场（MF）的影响下，SAB能够靶向并富集于肿瘤部位。在肿瘤中释放的SAB能够有效抑制TAFs产生细胞外基质（ECM），促进T细胞浸润，并诱导抗肿瘤免疫反应。最终，PMNP-SAB@RTM与BMS-1（PD-1/PD-L1抑制剂1）联合使用能够有效抑制肿瘤生长。最后，本研究基于“冷”和“热”微环境的区分，为TNBC免疫治疗提出了一种精确有效的新策略。
