pH 响应型锌离子调节免疫调节纳米颗粒用于有效的癌症免疫治疗,Biomacromolecules

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pH 响应型锌离子调节免疫调节纳米颗粒用于有效的癌症免疫治疗
Biomacromolecules ( IF 5.5 ) Pub Date : 2023-08-24 , DOI: 10.1021/acs.biomac.3c00557
Byoungjun Lim _{1,

2} , Kyoung Sub Kim ₂ , Kun Na _{1,

2}

Affiliation

在此，我们介绍了一种新方法，涉及利用含有光敏剂（HPZ）的人血清白蛋白包被的沸石咪唑酯骨架-8，该光敏剂具有对肿瘤微环境的靶向识别，能够快速升高锌离子浓度，同时促进控释封装的光敏剂（PS）。在生理 pH 值为 7.4 时，HPZ 的大小约为 170 nm，在 pH 6.5 酸性条件下显着减小至小于 10 nm。酸诱导的 HPZ 分解会引发锌离子浓度快速增加，从而对结直肠癌、乳腺癌和胰腺癌产生有效的细胞毒性作用。此外，在激光照射下，HPZ 内封装的 PS 会引发活性氧的产生，协同增强锌离子诱导的细胞毒性。在 CT26 荷瘤小鼠模型中静脉注射 HPZ 导致 CD3 ⁺ CD4 ⁺辅助 T 细胞和 CD3 ⁺ CD8 ^{+细胞毒性 T 细胞显着扩增，同时 CD4}⁺ CD25 ⁺ Foxp3 ⁺调节性 T 细胞减少人口。这些变化导致了肿瘤生长的显着抑制，凸显了 HPZ 在该实验模型中的功效。重要的是，HPZ 表现出良好的安全特性，对重要器官没有毒性，并且不会导致体重减轻。因此，HPZ 作为独立治疗或与多种抗癌免疫疗法联合使用具有巨大的前景，凸显了其在抗癌免疫治疗领域的潜力。

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pH-Responsive Zinc Ion Regulating Immunomodulatory Nanoparticles for Effective Cancer Immunotherapy

Herein, we introduce a novel approach involving the utilization of a human serum albumin-coated zeolite imidazolate framework-8 containing a photosensitizer (HPZ) that exhibits targeted recognition of the tumor microenvironment, enabling the rapid elevation of zinc ion concentrations while facilitating the controlled release of an encapsulated photosensitizer (PS). At a physiological pH of 7.4, HPZ demonstrates a size of approximately 170 nm, significantly decreasing to less than 10 nm under pH 6.5 acidic conditions. Acid-induced decomposition of HPZ triggers a rapid increase in zinc ion concentration, eliciting potent cytotoxic effects against colorectal, breast, and pancreatic cancers. Additionally, upon laser irradiation, the encapsulated PS within HPZ initiates the generation of reactive oxygen species, synergistically augmenting the cytotoxicity induced by zinc ions. Intravenous administration of HPZ in a CT26 tumor-bearing mouse model resulted in a notable expansion of CD3⁺CD4⁺ helper T cells and CD3⁺CD8⁺ cytotoxic T cells, accompanied by a reduction in the CD4⁺CD25⁺Foxp3⁺ regulatory T-cell population. These changes led to significant inhibition of tumor growth, highlighting the efficacy of HPZ in this experimental model. Importantly, HPZ exhibits favorable safety characteristics, displaying no toxicity toward vital organs and inducing no weight loss. Thus, HPZ holds immense promise as a standalone treatment or in combination with diverse anticancer immunotherapies, underscoring its potential in the field of anticancer immunotherapy.

更新日期：2023-08-24

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