DataVXAdvanced MaterialsPaper
journal article·2022-10Open access

A pH‐Responsive Cluster Metal–Organic Framework Nanoparticle for Enhanced Tumor Accumulation and Antitumor Effect

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

Advanced Materials· Volume 34· Issue 42
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Source abstract

Abstract

Abstract As a result of the deficient tumor‐specific antigens, potential off‐target effect, and influence of protein corona, metal–organic framework nanoparticles have inadequate accumulation in tumor tissues, limiting their 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 nanoshell to coat apilimod (Ap)‐loaded zeolitic imidazolate framework (Ap‐ZIF) to form Ap‐ZIF@SLN#L. Under the tumor microenvironment, the hydrophilic PEG and MMfu are removed, exposing the hydrophobic OA on Ap‐ZIF@SLN#L, increasing their uptake in cancer cells and accumulation in the tumor. The ZIF@SLN#L nanoparticle induces reactive oxygen species (ROS). Ap released from Ap‐ZIF@SLN#L significantly promotes intracellular ROS and lactate dehydrogenase generation. Ap‐ZIF@SLN#L inhibits tumor growth, increases the survival rate in mice, activates the tumor microenvironment, and improves the infiltration of macrophages and T cells in the tumor, as demonstrated in two different tumor‐bearing mice after injections with Ap‐ZIF@SLN#TL. Furthermore, mice show normal tissue structure 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.
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Research context

Nanomaterials

OpenAlex topics: Nanoplatforms for cancer theranostics · Cancer Research and Treatments · Nanoparticle-Based Drug Delivery

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of General Surgery Pancreatic Disease Center Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin Second Road Shanghai 200025 P. R. China

Department of Biomedical Engineering W.J. Korf Institute for Biomedical Engineering and Materials Science University Medical Center Groningen/University of Groningen Groningen 9713 AV The Netherlands

Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases Shanghai Institute of Traumatology and Orthopaedics Ruijin Hospital Shanghai Jiao Tong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 P. R. China

Drug Research Program Division of Pharmaceutical Chemistry and Technology Faculty of Pharmacy University of Helsinki Helsinki FI‐00014 Finland

Research Institute of Pancreatic Diseases Shanghai Jiaotong University School of Medicine 197 Ruijin 2nd Road Shanghai 200025 China

Laboratory of Industrial Physics Department of Physics University of Turku Turku FI‐20014 Finland

Pharmaceutical Sciences Laboratory Åbo Akademi University Turku FI‐20520 Finland

Turku Biosciences Center University of Turku and Åbo Akademi University Turku FI‐20520 Finland

Funding

National Key Research and Development Program of China · National Natural Science Foundation of China · Academy of Finland · China Scholarship Council

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