An Enzyme-responsive Porphyrin Metal-organic Framework Nanosystem for Targeted and Enhanced Synergistic Cancer Photo-chemo Therapy.

Current drug delivery Pub Date : 2024-02-27 DOI:10.2174/0115672018286563240223072702

Mengqi Yi, Yangxin Lin, Yuyang Li, Bei Xiong, Yunhan Huang, Wei Guo, Bo Lu

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Abstract

Background: The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting.

Objective: The goal of the current research was to create a biocompatible GSH-depleting and tumor- targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy.

Methods: The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells.

Results: The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells in vitro. DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of 2.71 μg mL-1.

Conclusion: This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

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一种酶响应卟啉金属有机框架纳米系统，用于靶向和增强癌症光化学疗法的协同作用。

背景：光动力疗法（PDT）联合化疗的临床疗效已被证明是一种很有前景的肿瘤治疗策略，但却受到肿瘤部位谷胱甘肽（GSH）浓度过高和非特异性药物靶向的限制：当前研究的目标是为光动力和化疗联合疗法创造一种生物相容性好的GSH消耗和肿瘤靶向纳米粒子（标记为DOX/CA@PCN-224@HA）：方法：采用透射电子显微镜（TEM）对纳米粒子进行表征。采用紫外可见分光光度计测量药物负载效率（DE）和封装效率（EE）。使用 Ellman 试验测量了 GSH 的消耗能力。共聚焦激光扫描显微镜（CLSM）用于评估细胞摄取情况。采用 MTT 评估 DOX/CA@PCN-224@HA 对 4T1 细胞的细胞毒性：结果：改变后的 PCN-224 显示出良好的单分散性，长度约为 193 nm ± 2 nm，宽度约为 79 nm ± 3 nm。与其他球形 PCN-224 纳米颗粒相比，PCN-224 更大的纺锤网格状结构具有更好的双药负载能力（DOX：20.58%±2.60%，CA：21.81%±1.98%）。72小时后，DOX/CA@PCN-224@HA在透明质酸酶（HAase）作用下的最终累积药物释放率分别为74%±1%（DOX）和45%±2%（CA）。通过生物学评价，载药纳米粒子能准确靶向4T1细胞。此外，释放的 DOX 和 CA 在体外对 4T1 细胞有协同作用。DOX/CA@PCN-224@HA 纳米颗粒对 4T1 细胞有抑制作用，IC50 值为 2.71 μg mL-1：该纳米系统在肿瘤靶向增强（光化学疗法）治疗方面具有巨大潜力。

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Current drug delivery

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