A pH-Responsive Cluster Metal-Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect
| Autor: | Ruoyu Cheng, Lingxi Jiang, Han Gao, Zehua Liu, Ermei Mäkilä, Shiqi Wang, Qimanguli Saiding, Lei Xiang, Xiaomei Tang, Minmin Shi, Jia Liu, Libin Pang, Jarno Salonen, Jouni Hirvonen, Hongbo Zhang, Wenguo Cui, Baiyong Shen, Hélder A. Santos |
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| Rok vydání: | 2022 |
| Předmět: |
Targeting
Metal-organic framework pH-Responsive targeting Mechanical Engineering Alanine Transaminase Hydrogen-Ion Concentration Lipids Polyethylene Glycols Mice Mechanics of Materials Neoplasms Zeolites Tumor Microenvironment Animals Nanoparticles General Materials Science Protein Corona Aspartate Aminotransferases Reactive Oxygen Species Lactate Dehydrogenases Metal-Organic Frameworks Cancer Maleic Anhydrides |
| Zdroj: | Advanced materials, 34(42):2203915. WILEY-V C H VERLAG GMBH |
| ISSN: | 1521-4095 0935-9648 |
| Popis: | As a result of the deficient tumor-specific antigens, potential off-target effect, and influence of protein corona, the metal-organic framework nanoparticles have inadequate accumulation in the tumor tissues, limiting the therapeutic effects. In this work, a pH-responsive linker (L) is prepared by covalently modifying oleylamine (OA) with 3-(bromomethyl)-4-methyl-2,5-furandione (MMfu) and poly (ethylene glycol) (PEG). Then, the L is embedded into a solid lipid nano-shell to coat apilimod (Ap)-loaded zeolitic imidazolate framework (Ap-ZIF) to form Ap-ZIF@SLNL. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap-ZIF@SLNL, increasing their uptake in cancer cells and accumulation in the tumor. ZIF@SLNL nanoparticle induced reactive oxygen species (ROS). Ap released from Ap-ZIF@SLNL significantly promoted intracellular ROS and lactate dehydrogenase generation. Ap-ZIF@SLNL inhibited tumor growth, increased the survival rate in mice, activated the tumor microenvironment, and improved the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor-bearing mice after injections with Ap-ZIF@SLNTL. Furthermore, mice showed normal physiological responses of the main organs and the normal serum level in alanine aminotransferase and aspartate aminotransferase after treatment with the nanoparticles. Overall, this pH-responsive targeting strategy improves nanoparticle accumulation in tumors with enhanced therapeutic effects. This article is protected by copyright. All rights reserved |
| Databáze: | OpenAIRE |
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