School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Nano Lett. 2021 Jul 28;21(14):6031-6041. doi: 10.1021/acs.nanolett.1c01210. Epub 2021 Jul 9.
Triple-negative breast cancer (TNBC) is an aggressive disease with a high recurrence rate and poor outcomes in clinic. In this study, inspired by the enriched innate immune cell type tumor-associated macrophages (TAMs) in TNBC, we proposed a matrix metalloprotease 2 (MMP2) responsive integrated immunochemotherapeutic strategy to deliver paclitaxel (PTX) and anti-CD47 (aCD47) by detachable immune liposomes (ILips). In the TNBC microenvironment, the "two-in-one" ILips facilitated MMP2-responsive release of aCD47 to efficiently polarize M2 macrophages toward the M1 phenotype to enhance phagocytosis against tumor cells and activate the systemic T cell immune response. Together with the immune effect, the detached PTX-loaded liposomes were internalized in MDA-MB-231 cells to synergistically inhibit tumor cell proliferation and metastasis. In the TNBC-bearing mouse model, PTX-loaded ILips demonstrated superior antitumor efficacy against TNBC and inhibited tumor recurrence. Our integrated strategy represents a promising approach to synchronously enhance immune response and tumor-killing effects, improving the therapeutic efficacy against TNBC.
三阴性乳腺癌(TNBC)是一种侵袭性疾病,临床上复发率高,预后差。在这项研究中,受 TNBC 中富含固有免疫细胞类型肿瘤相关巨噬细胞(TAMs)的启发,我们提出了一种基质金属蛋白酶 2(MMP2)响应性集成免疫化疗策略,通过可分离免疫脂质体(ILips)递送紫杉醇(PTX)和抗 CD47(aCD47)。在 TNBC 微环境中,“二合一”ILips 促进 MMP2 响应性释放 aCD47,有效地将 M2 巨噬细胞极化为 M1 表型,增强对肿瘤细胞的吞噬作用,并激活全身 T 细胞免疫反应。与免疫效果一起,分离的载有 PTX 的脂质体被 MDA-MB-231 细胞内化,协同抑制肿瘤细胞增殖和转移。在 TNBC 荷瘤小鼠模型中,载有 PTX 的 ILips 对 TNBC 表现出优异的抗肿瘤疗效,并抑制肿瘤复发。我们的集成策略代表了一种有前途的方法,可以同步增强免疫反应和肿瘤杀伤效应,提高对 TNBC 的治疗效果。
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