氧化响应型多金属有机骨架纳米粒子用于增强 STING 激活的光动力-免疫联合治疗。
Oxidation-Responsive PolyMOF Nanoparticles for Combination Photodynamic-Immunotherapy with Enhanced STING Activation.
机构信息
School of Chemistry, Engineering Research Center of Energy Storage Materials and Devices, Ministry of Education, Xi'an Jiaotong University, Xi'an 710049, Shaanxi, China.
CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, Anhui, China.
出版信息
ACS Nano. 2023 May 23;17(10):9374-9387. doi: 10.1021/acsnano.3c01333. Epub 2023 May 4.
Stimulator of interferon genes (STING) activation by STING agonists has been recognized as one of the potent and promising immunotherapy strategies. However, the immunosuppressive tumor microenvironment always hinders the therapeutic efficacy of cancer immunotherapy. In this report, we present polymeric metal-organic framework (PMOF) nanoparticles (NPs) for the combination of photodynamic therapy (PDT) and enhanced STING activation to improve the immunotherapeutic efficacy. The PMOF NPs with poly(ethylene glycol) (PEG) shells were obtained via coordination between the block copolymer ligand PEG--PABDA consisting of 1,4-bezenedicarboxylic acid-bearing polyacrylamide (PABDA), meso-tetra(carboxyphenyl)porphyrin (TCPP), thioketal diacetic acid, and zirconyl chloride. Subsequently, the STING agonist SR-717 was loaded into the porous structure of PMOF to obtain SR@PMOF NPs which show excellent stability under the physiological conditions. After intravenous injection and tumor accumulation, light irradiation on the tumor sites results in efficient singlet oxygen (O) production from TCPP and cellular apoptosis to release fragmented DNA and tumor-associated antigens. Simultaneously, thioketal bonds can be broken by O to destroy the PMOF structure and rapidly release SR717. SR-717 and PDT synergistically enhance the antitumor immunity via combination photodynamic-immunotherapy due to reversal of the immunosuppressive tumor microenvironment and enhanced endogenous STING activation, which can suppress the growth of the primary and distant tumors efficiently. The oxidation-responsive SR@PMOF NPs represent a promising delivery system of STING agonists and efficient PDT NPs for simultaneous suppression of the primary and metastatic tumors via the rational combination of PDT and enhanced STING activation.
干扰素基因刺激物 (STING) 激动剂激活 STING 已被认为是一种强有力且有前途的免疫治疗策略。然而,免疫抑制性肿瘤微环境总是阻碍癌症免疫治疗的疗效。在本报告中,我们提出了聚合金属-有机框架 (PMOF) 纳米粒子 (NPs),用于光动力治疗 (PDT) 和增强 STING 激活的联合,以提高免疫治疗效果。PMOF NPs 具有聚乙二醇 (PEG) 壳,通过包含 1,4-苯二甲酸的嵌段共聚物配体 PEG-PABDA 与间四(羧基苯基)卟啉 (TCPP)、硫缩酮二乙酸和氯化锆之间的配位获得,PMOF NPs 具有聚乙二醇 (PEG) 壳。随后,将 STING 激动剂 SR-717 装入 PMOF 的多孔结构中,得到 SR@PMOF NPs,在生理条件下具有优异的稳定性。静脉注射并在肿瘤部位积累后,在肿瘤部位进行光照会导致 TCPP 产生有效的单线态氧 (O) 并导致细胞凋亡,从而释放断裂的 DNA 和肿瘤相关抗原。同时,O 可以破坏硫缩酮键来破坏 PMOF 结构并迅速释放 SR717。SR-717 和 PDT 通过联合光动力免疫疗法协同增强抗肿瘤免疫,因为逆转了免疫抑制性肿瘤微环境并增强了内源性 STING 激活,从而可以有效地抑制原发性和转移性肿瘤的生长。氧化响应性 SR@PMOF NPs 代表了一种有前途的 STING 激动剂递送系统和高效 PDT NPs,可通过 PDT 和增强 STING 激活的合理联合来同时抑制原发性和转移性肿瘤。