Mannosylated polylactic-co-glycolic acid (MN-PLGA) nanoparticles induce potent anti-tumor immunity in murine model of breast cancer - 18/09/21
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Abstract |
Nanoparticle-based cancer immunotherapy is considered a novel and promising therapeutic strategy aimed at stimulating host immune responses against tumors. To this end, in the present study, mannan-decorated polylactic-co-glycolic acid (PLGA) nanoparticles containing tumor cell lysate (TCL) and poly riboinosinic polycytidylic acid (poly I:C) were used as antigen delivery systems to immunize breast tumor-bearing Balb/c mice. PLGA nanoparticles were fabricated employing a double emulsion solvent evaporation method. The formation of spherical and uniform nanoparticles (NPs) ranging 150–250 nm was detected by field emission scanning electron microscopy (FESEM) and dynamic light scattering (DLS). Four nanoformulation were used to treat mice and vaccination-induced immunological responses. Tumor regression and overall survival rate were evaluated in four experimental groups. Tumor cell lysate and poly I:C loaded mannan-decorated nanoparticles (TCL-Poly I:C) NP-MN caused a significant decrease in tumor growth and 2- to 3-fold improvement in survival times of the treated mice. The NPs with or without mannan decoration elicited stronger responses in terms of lymphocyte proliferation, delayed-type hypersensitivity and CD107a expression. Moreover, our data indicated that the production of IFN-γ and IL-2 increased while the production of IL-4 and IL-10 decreased in splenocytes culture supernatants. In the pathological evaluations, we found that necrosis and immune cells infiltration rate in the tumor tissue of the treated mice was elevated, while tumor cellularity and lung metastases significantly decreased in particular in the group that received (TCL-Poly I:C) NP-MN. Altogether, our findings suggested that the mannan-decorated PLGA NPs antigen delivery system had significant anti-tumor effects against the murine model of breast cancer and it could be considered as a step forward to human breast cancer immunotherapy.
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Highlights |
• | Mannan-decorated PLGA nanoparticles containing breast tumor cell lysate and poly I:C were manufactured to treat breast cancer in Balb/c mice. |
• | Manufactured nanoparticles induced strong tumor-specific cellular and humoral immunity. |
• | Tumor cell lysate and poly I:C loaded mannan-decorated nanoparticles elicited a significant decrease in tumor growth and 2–3-fold improvement in survival times of the treated mice. |
• | This nano-based delivery system could be used as an efficient method for breast cancer treatment as well as a step forward to human breast cancer immunotherapy. |
Abbreviations : APC, CA 15-3, CEA, CTL, DC, DLS, DTH, E-NP, FDA, FESEM, LDH, MN, MN-PLGA, MR, MSBR, NC, PLGA, poly I:C, TAA, TC, TCL, TCL-poly I:C, TCL-NP, TCL-poly I:C NP, TCL-poly I:C NP-MN, Th, TSA
Keywords : Immunotherapy, PLGA nanoparticles, Tumor cell lysate, Poly I:C, Mannan, Breast cancer
Plan
Vol 142
Article 111962- octobre 2021 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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