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 stability in a neutral environment, pH-triggered drug release, as well as enhanced penetration and destruction against 3D
tumor spheroids, thereby making targeted
cancer therapy possible.