Chen Xinxin, Sun Jiang, Ye Tingxian, Li Fanzhu
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
Jinhua Academy of Zhejiang Chinese Medical University, Jinhua 321015, China.
Pharmaceutics. 2025 May 5;17(5):614. doi: 10.3390/pharmaceutics17050614.
: , a tumor-resident bacterium colonizing breast cancer (BC), results in an immunosuppressive microenvironment and facilitates tumor growth and metastasis. This study aimed to develop a neutrophil-based liposome delivery system designed for dual-targeted elimination of tumor cells and , while simultaneously upregulating pathogen-associated molecular patterns and damage-associated molecular patterns to potentiate tumor immunotherapy. : The liposomes (PD/GA-LPs) loaded with the perylene diimide complex (PD) and gambogic acid (GA) were fabricated via the extrusion method. Subsequently, comprehensive evaluations including physicochemical characteristics, antibacterial activity, antitumor effect, and immunomodulatory effect evaluation were systematically conducted to validate the feasibility of this delivery system. : The resulting PD/GA-LPs exhibited a dynamic size (121.3 nm, zeta potential -44.1 mV) and a high encapsulation efficiency of approximately 78.1% (PD) and 91.8% (GA). In addition, the optimized PD/GA-LPs exhibited excellent photothermal performance and antibacterial efficacy. In vitro cellular experiments revealed that PD/GA-LPs exhibited enhanced internalization by neutrophils, followed by extracellular trap-mediated release, ultimately significantly inhibiting tumor cell proliferation and inducing immunogenic cell death. During in vivo treatment, PD/GA-LPs exhibited targeted tumor accumulation, where -driven PD reduction activated near-infrared-responsive photothermal ablation. When combined with GA, this delivery system effectively eliminated tumor cells and , while facilitating the subsequent T-cell infiltration. : This strategy amplified the antitumor immune response, thus leading to effective treatment of BC and prevention of metastasis. In summary, this approach, grounded in the distinct microecology of tumor and normal tissues, offers novel insights into the development of precise and potent immunotherapies for BC.
粪肠球菌是一种定植于乳腺癌（BC）的肿瘤驻留细菌，会导致免疫抑制微环境并促进肿瘤生长和转移。本研究旨在开发一种基于中性粒细胞的脂质体递送系统，用于双重靶向消除肿瘤细胞和粪肠球菌，同时上调病原体相关分子模式和损伤相关分子模式以增强肿瘤免疫治疗。方法：通过挤压法制备负载苝二亚胺复合物（PD）和藤黄酸（GA）的脂质体（PD/GA-LPs）。随后，系统地进行了包括物理化学特性、抗菌活性、抗肿瘤作用和免疫调节作用评估在内的综合评价，以验证该递送系统的可行性。结果：所得的PD/GA-LPs呈现出动态大小（121.3nm，zeta电位-44.1mV）以及约78.1%（PD）和91.8%（GA）的高包封率。此外，优化后的PD/GA-LPs表现出优异的光热性能和抗菌效果。体外细胞实验表明，PD/GA-LPs被中性粒细胞摄取增强，随后通过细胞外陷阱介导释放，最终显著抑制肿瘤细胞增殖并诱导免疫原性细胞死亡。在体内治疗期间，PD/GA-LPs表现出靶向肿瘤蓄积，其中粪肠球菌驱动的PD减少激活了近红外响应光热消融。当与GA联合使用时，该递送系统有效地消除了肿瘤细胞和粪肠球菌，同时促进了随后的T细胞浸润。结论：该策略放大了抗肿瘤免疫反应，从而有效治疗BC并预防转移。总之，这种基于肿瘤和正常组织不同微生态的方法为开发精确有效的BC免疫疗法提供了新的见解。
