Tianjin Key Laboratory of Biomedical Materials, Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.
J Nanobiotechnology. 2022 Mar 18;20(1):140. doi: 10.1186/s12951-022-01353-5.
Chemotherapeutics that can trigger immunogenic cell death (ICD) and release tumor-specific antigens are effective on treating a variety of cancers. The codelivery of chemotherapeutics with adjuvants is a promising strategy to achieve synergistic therapeutic effect. However, low drug loading and complicated preparation of current delivery systems lead to carrier-associated toxicity and immunogenicity. Herein, we developed a facile approach to construct liposomal spherical nucleic acids (SNA) by the self-assembly of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE)-doxorubicin conjugate and DOPE-matrix metalloproteinases-9 (MMP-9) responsive peptide-CpG conjugate (DOPE-MMP-CpG). Liposomal SNAs efficiently co-delivered DOX and CpG into tumors and released the two drugs upon biological stimuli of MMP-9 enzyme in tumor microenvironment (TME) and high concentration of endogenous glutathione in tumor cells. We demonstrated that liposomal SNA enhanced activation of dendritic cells (DCs), promoted expansion of CD8 and CD4 T cells in both tumors and spleen, inhibited tumor growth, and extended animal survival. This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors with synergistic therapeutic effect and reduced side effect.
能够引发免疫原性细胞死亡 (ICD) 并释放肿瘤特异性抗原的化疗药物对治疗多种癌症有效。化疗药物与佐剂的共递送是实现协同治疗效果的一种很有前途的策略。然而，目前递送系统的载药量低且制备复杂，导致载体相关的毒性和免疫原性。在此，我们开发了一种简便的方法，通过 1,2-二油酰基-sn-甘油-3-磷酸乙醇胺 (DOPE)-阿霉素偶联物和 DOPE-基质金属蛋白酶-9 (MMP-9) 响应肽-CpG 偶联物 (DOPE-MMP-CpG) 的自组装构建脂质体球形核酸 (SNA)。脂质体 SNA 能够有效地将 DOX 和 CpG 共递送入肿瘤，并在肿瘤微环境 (TME) 中 MMP-9 酶和肿瘤细胞中内源性谷胱甘肽的高浓度的生物刺激下释放这两种药物。我们证明，脂质体 SNA 增强了树突状细胞 (DC) 的激活，促进了肿瘤和脾脏中 CD8 和 CD4 T 细胞的扩增，抑制了肿瘤生长，并延长了动物的存活期。这项工作提供了一种将化疗药物和佐剂递送到肿瘤的简单策略，具有协同的治疗效果和降低的副作用。
