posted on 2024-01-18, 16:36authored bySiyu Meng, Huiping Du, Xiang Li, Xinmin Zheng, Pan Zhao, Zhang Yuan, Shaohui Huang, Yanli Zhao, Liangliang Dai
Immunotherapy
is restricted by a complex tumor immunosuppressive
microenvironment (TIM) and low drug delivery efficiency. Herein, a
multifunctional adjuvant micelle nanosystem (PPD/MPC) integrated with
broken barriers and re-education of three classes of immune-tolerant
cells is constructed for cancer immunotherapy. The nanosystem significantly
conquers the penetration barrier via the weakly acidic tumor microenvironment-responsive
size reduction and charge reversal strategy. The detached core micelle
MPC could effectively be internalized by tumor-associated macrophages
(TAMs), tumor-infiltrating dendritic cells (TIDCs), and myeloid-derived
suppressor cells (MDSCs) via mannose-mediated targeting endocytosis
and electrostatic adsorption pathways, promoting the re-education
of immunosuppressive cells for allowing them to reverse from pro-tumor
to antitumor phenotypes by activating TLR4/9 pathways. This process
in turn leads to the remodeling of TIM. In vitro and in vivo studies
collectively indicate that the adjuvant micelle-based nanosystem not
only relieves the intricate immune tolerance and remodels TIM via
reprogramming the three types of immunosuppressive cells and regulating
the secretion of relevant cytokines/immunity factors but also strengthens
immune response and evokes immune memory, consequently suppressing
the tumor growth and metastasis.