Multistage-responsive nanovehicle to improve tumor penetration for dual-modality imaging-guided photodynamic-immunotherapy
Multistage-responsive nanovehicle to improve tumor penetration for dual-modality imaging-guided photodynamic-immunotherapy
复制标题
多级响应纳米载体可提高双模成像引导光动力免疫治疗的肿瘤渗透性
DOI：
10.1016/j.biomaterials.2021.120990
复制
发表时间：
2021-06-26
期刊：
影响因子：
14
通讯作者：
Liu, Yiyao
中科院分区：
文献类型：
--
作者：
Feng, Yi;Xie, Xiaoxue;Liu, Yiyao
The exploration of an intelligent multifunctional imaging-guided therapeutic platform is of great significance because of its ideal delivery efficiency and controlled release. In this work, a tumor microenvironment (TME)responsive nanocarrier (denoted as MB@MSP) is designed for on-demand, sequentially release of a short Dpeptide antagonist of programmed cell death-ligand 1 (named as PDPPA-1) and a photosensitizer methylene blue (MB). Fe3O4-Au located in the core of MB@MSP is used as a magnetic resonance imaging and micro-computed tomography imaging contrast agent for noninvasive diagnosis of solid tumors and simultaneous monitoring of drug delivery. The PDPPA-1 coated on MB@MSP can be shed due to the cleavage of the peptide substrate by matrix metalloproteinase-2 (MMP-2) that is highly expressed in the tumor stroma, and disulfide bonding is further broken when it encounters high levels of glutathione (GSH) in TME, which finally leads to significant size reduction and charge-reversal. These transitions facilitate penetration and uptake of nanocarriers against tumors. Noticeably, the released PDPPA-1 can block the immune checkpoint to create an environment that favors the activation of cytotoxic T lymphocytes and augment the antitumor immune response elicited by photodynamic therapy, thus significantly improving therapeutic outcomes. Studies of the underlying mechanisms suggest that the designed MMP-2 and GSH-sensitive delivery system not only induce apoptosis of tumor cells but also modulate the immunosuppressive tumor microenvironment to eventually augment the suppression tumor metastasis effect of CD8+ cytotoxic T cells. Overall, the visualization of the therapeutic processes with comprehensive information renders MB@MSP an intriguing platform to realize the combined treatment of metastatic tumors.
