Affiliation:
1. Department of Geriatric Dentistry Beijing Laboratory of Biomedical Materials Peking University School and Hospital of Stomatology Beijing 100081 China
2. Biomedical Engineering Department Peking University Beijing 100191 China
3. Centre for Advanced Macromolecular Design and Australian Centre for NanoMedicine School of Chemical Engineering The University of New South Wales Sydney New South Wales 2052 Australia
4. Institute of Medical Technology Health Science Center of Peking University Beijing 100191 China
5. Peking University‐Yunnan Baiyao International Medical Research Center Beijing 100191 China
6. Peking University International Cancer Institute Beijing 100191 China
Abstract
AbstractProtein drugs are increasingly used as therapeutics for the treatment of cancer. However, their inherent drawbacks, such as poor stability, low cell membrane and tissue permeability, lack of tumor selectivity, and severe side effects, limit their wide applications in cancer therapy. Herein, screening of a thermo‐pH‐sensitive polymer–glucose oxidase conjugate that can controllably self‐assemble into nanoparticles with improved stability is reported. The size, surface charge, and bioactivity of the conjugate can be tuned by adjustment of the solution temperature and pH. The cellular uptake, intracellular hydrogen peroxide generation, and tumor cell spheroid penetration of the conjugate are greatly enhanced under the acidic tumor microenvironment, leading to increased cytotoxicity to tumor cells. Upon a single intratumoural injection, the conjugate penetrates into the whole tumor tissue but hardly diffuses into the normal tissues, resulting in the eradication of the tumors in mice without perceivable side effects. Simultaneously, the conjugate induces a robust antitumor immunity to efficiently inhibit the growth of distant tumors, especially in combination with an immune checkpoint inhibitor. These findings provide a novel and general strategy to make multifunctional protein‐polymer conjugates with responsiveness to the acidic tumor microenvironment for selective tumor therapy.
Funder
National Natural Science Foundation of China
Subject
Mechanical Engineering,Mechanics of Materials,General Materials Science
Cited by
6 articles.
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