Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer

Abstract

Background Mono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. Results Poly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with “Nano-targeted cells”-based cocktail therapy. Conclusion “Nano-targeted cells”-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence. Graphical Abstract

Cancer cell membrane-wrapped nanoparticles for cancer immunotherapy: A review of current developments

“…In another such study, Chen et al. reported a cocktail therapy based on “nano-targeted cells” ( 36 ). In this therapy, PTT was triggered by laser irradiation and helped the release of tumor-associated antigens (TAAs), thereby enhancing docetaxel-mediated immune effects ( 36 ).…”

“…reported a cocktail therapy based on “nano-targeted cells” ( 36 ). In this therapy, PTT was triggered by laser irradiation and helped the release of tumor-associated antigens (TAAs), thereby enhancing docetaxel-mediated immune effects ( 36 ). The released TAAs, together with the immune adjuvant R837, drove the maturation of DCs and secretion of cytokines, including TNF-α, IL-6, and IL-12 ( 36 ).…”

“…In this therapy, PTT was triggered by laser irradiation and helped the release of tumor-associated antigens (TAAs), thereby enhancing docetaxel-mediated immune effects ( 36 ). The released TAAs, together with the immune adjuvant R837, drove the maturation of DCs and secretion of cytokines, including TNF-α, IL-6, and IL-12 ( 36 ). Furthermore, docetaxel polarized protumoral M2-phenotype tumor-associated macrophages (TAMs) to tumoricidal M1-phenotype TAMs; this alleviated immunosuppression in the TME and was accompanied by a decrease in IL-10 ( 36 ).…”

“…The released TAAs, together with the immune adjuvant R837, drove the maturation of DCs and secretion of cytokines, including TNF-α, IL-6, and IL-12 ( 36 ). Furthermore, docetaxel polarized protumoral M2-phenotype tumor-associated macrophages (TAMs) to tumoricidal M1-phenotype TAMs; this alleviated immunosuppression in the TME and was accompanied by a decrease in IL-10 ( 36 ). The above processes promoted the infiltration of CTLs for the treatment of distant metastasis ( 36 ).…”

“…Furthermore, docetaxel polarized protumoral M2-phenotype tumor-associated macrophages (TAMs) to tumoricidal M1-phenotype TAMs; this alleviated immunosuppression in the TME and was accompanied by a decrease in IL-10 ( 36 ). The above processes promoted the infiltration of CTLs for the treatment of distant metastasis ( 36 ). Fang et al.…”