Hyaluronic acid nanogels prepared via ortho ester linkages show pH-triggered behavior, enhanced penetration and antitumor efficacy in 3-D tumor spheroids

Journal of Colloid and Interface Science
Guanqing YangRupei Tang

Abstract

A new type of pH-triggered hyaluronic acid nanogel system (HA-NGs) was successfully developed for tumor-targeted delivery of drugs. HA-NGs were obtained by copolymerization between methacrylate HA and a new cross-linker containing ortho ester groups in an aqueous solution. The therapeutic drug (DOX) was loaded into the HA-NGs (DOX@HA-NGs) and exhibited appropriate loading of about 17.3% with a size of around 200nm. Such new pH-triggered HA-NGs are found to be highly desirable for targeted cancer therapy because it could significantly minimize the amount of premature drug release in neutral pH, and also provide a sufficient amount of drug to effectively kill the cancer cells caused by the degradation of ortho ester groups at acid pH values. Results from the cellular uptake and cytotoxicity of DOX@HA-NGs performed in two-dimensional (2D) cell culture demonstrated that DOX@HA-NGs exhibit excellent tumor homing and higher cytotoxicity. Importantly, the penetration and inhibition against three-dimensional (3D) tumor spheroids demonstrated that DOX@HA-NGs could fully penetrate into HepG2 tumor spheroids, thus leading to higher inhibition. So, such new tumor-targeting DOX@HA-NGs prepared via ortho ester linkages will exhibit excellent...Continue Reading

Citations

Jul 3, 2019·Pharmaceutics·Kibeom KimJa-Hyoung Ryu
Mar 11, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Somayeh RezaeiMarjan Motiei
Dec 12, 2020·Biomaterials Science·Zhen LiJun Wu
Jun 3, 2021·Gels·Brielle StawickiHyunah Cho
Aug 9, 2021·International Journal of Biological Macromolecules·Xu ChengRupei Tang
Aug 24, 2021·Carbohydrate Polymers·Asghar Narmani, Seid Mahdi Jafari

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