posted on 2024-01-25, 13:34authored byLu Tang, Cong Fu, Hening Liu, Yue Yin, Yuqi Cao, Jingwen Feng, Aining Zhang, Wei Wang
Surgery is the primary method to treat malignant melanoma;
however,
the residual microtumors that cannot be resected completely often
trigger tumor recurrence, causing tumor-related mortality following
melanoma resection. Herein, we developed a feasible strategy based
on the combinational chemoimmunotherapy by cross-linking carboxymethyl
chitosan (CMCS)-originated polymetformin (PolyMetCMCS)
with cystamine to prepare stimuli-responsive nanogel (PMNG) owing
to the disulfide bond in cystamine that can be cleaved by the massive
glutathione (GSH) in tumor sites. Then, chemotherapeutic agent doxorubicin
(DOX) was loaded in PMNG, which was followed by a hyaluronic acid
coating to improve the overall biocompatibility and targeting ability
of the prepared nanogel (D@HPMNG). Notably, PMNG effectively reshaped
the tumor immune microenvironment by reprogramming tumor-associated
macrophage phenotypes and recruiting intratumoral CD8+ T
cells owing to the inherited immunomodulatory capability of metformin.
Consequently, D@HPMNG treatment remarkably suppressed melanoma growth
and inhibited its recurrence after surgical resection, proposing a
promising solution for overcoming lethal melanoma recurrence.