Polarization of Tumor-Associated Macrophages by Nanoparticle-Loaded Escherichia coli Combined with Immunogenic Cell Death for Cancer Immunotherapy.
Baicheng WeiJingmei PanRuiting YuanBinfen ShaoYi WangXing GuoShaobing ZhouPublished in: Nano letters (2021)
The tumor immunosuppressive microenvironment greatly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the tumor microenvironment, which can inhibit the tumor after converting it to an M1-like phenotype. In addition, immunogenic cell death (ICD) can increase the amount of T lymphocytes in tumors, activating antineoplastic immunity. Herein, tumor-associated macrophage polarization therapy supplemented with PLGA-DOX (PDOX)-induced ICD is developed for cancer treatment. The nanoparticles/bacteria complex (Ec-PR848) is fabricated for tumor targeting and TAM polarization, and PLGA-R848 (PR848) are attached to the surface of Escherichia coli (E. coli) MG1655 via electrostatic absorption. The toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) and E. coli can greatly polarize M2 macrophages to M1 macrophages, while PDOX-induced ICD can also impair the immunosuppression of the tumor microenvironment. This strategy shows that tumor-associated macrophage polarization therapy combined with ICD induced by low-dose chemotherapeutic drugs can commendably enhance the efficacy of immunotherapy.
Keyphrases
- escherichia coli
- toll like receptor
- cell death
- cell cycle arrest
- drug delivery
- low dose
- inflammatory response
- nuclear factor
- high glucose
- immune response
- diabetic rats
- cancer therapy
- stem cells
- induced apoptosis
- drug induced
- biofilm formation
- high dose
- klebsiella pneumoniae
- endothelial cells
- oxidative stress
- mesenchymal stem cells
- bone marrow
- wound healing