Delivery strategies and applications of HA-based delivery carriers. (A) The preparation of HAss nanogels and the targeting of HAss nanogels to RHAMM in cancer cell and lymph node which contains cancer cells with RHAMM overexpression. (B) Diagrammatic drawing of establishing lymph node metastases model in mouse and RBITC-HAss nanogels (red) penetrated in metastatic lymph node (left) and normal one (right) at 2 h post-injection ex vivo. The scale bar is 500 μm. (C) Immunofluorescence staining sections of RHAMM (green) expression in tumor, RBITC-HAss nanogels (red) penetrated in the tumor at 24 h post-injection. All cell nuclei are not shown in this figure. The scale bar is 100 μm. Adapted with permission from Yang C, Li C, Zhang P, Wu W, Jiang X. Redox Responsive Hyaluronic Acid Nanogels for Treating RHAMM (CD168) Over-expressive Cancer, both Primary and Metastatic Tumors. Theranostics. 2017;7(6):1719–1734. (https://creativecommons.org/licenses/by-nc/4.0/).243 (D) Graphic illustration of the preparation strategy and the antitumor function of HA-Zein-HNK nanoparticles. (E) The representative images and particle sizes of HA-Zein-HNK at different HA concentrations. (F) Expressions of pro-apoptotic proteins Bax and anti-apoptotic proteins Bcl-2 in 4T1 cells incubation with various HNK formulations. (G) The expressions of Vimentin and E-cadherin in 4T1 cells treated by Zein-HNK, HA-Zein-HNK, and free HNK were examined using western blot. Reprinted from Carbohydrate Polymers, 240, Zhang Q, Wang J, Liu D, et al. Targeted delivery of honokiol by zein/hyaluronic acid core-shell nanoparticles to suppress breast cancer growth and metastasis, 116325, Copyright 2020, with permission from Elsevier.118