3 years ago

Tailor-Making Fluorescent Hyaluronic Acid Microgels via Combining Microfluidics and Photoclick Chemistry for Sustained and Localized Delivery of Herceptin in Tumors

Tailor-Making
Fluorescent Hyaluronic Acid Microgels via Combining Microfluidics
and Photoclick Chemistry for Sustained and Localized Delivery of Herceptin
in Tumors
Ke Huang, Jian Zhang, Zhiyuan Zhong, Jing Chen, Chao Deng, Qijun Chen
Antibody therapeutics, though representing a most used biomedicine, suffers from poor in vivo stability, rapid degradation, and frequent injections. Here, we report that fluorescent hyaluronic acid microgels (HMGs) tailor-made by combining microfluidics and “tetrazole–alkene” photoclick chemistry enable sustained and localized delivery of Herceptin in ovarian tumors. HMGs were obtained with a defined size (25–50 μm), narrow size distribution, high stability, and strong green fluorescence. Notably, HMGs exhibited a remarkably high loading of proteins such as Herceptin and IgG with a loading efficiency exceeding 90% at a theoretical protein-loading content of 30 wt %. In vitro protein release experiments revealed a sustained and hyaluronidase (HAase)-dependent release of Herceptin from HMGs, in which 80.6% of Herceptin was released at 1 U/mL HAase in 10 days. The released Herceptin maintained its secondary structure and antitumor activity. In vivo imaging results demonstrated obviously better tumoral retention for Cy5-labeled Herceptin-loaded HMGs following subcutaneous (sc) injection than for the free-protein counterpart. Interestingly, sc injection of the Herceptin-loaded HMGs into SKOV-3 human ovarian tumor-bearing nude mice at a dose of 30 mg Herceptin equiv/kg induced nearly complete tumor suppression, which was significantly more effective than the sc or systemic injection of free Herceptin. These tailor-made fluorescent HMGs appeared as a robust injectable platform for sustained and localized delivery of therapeutic proteins.

Publisher URL: http://dx.doi.org/10.1021/acsami.7b15832

DOI: 10.1021/acsami.7b15832

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