Background: Single therapeutic modality always has its limitations in combating metastatic lesions with complicacy. Although the emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. Rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer.
Results: Poly lactic-co-glycolic acid (PLGA) nanospheres were constructed with photothermal transduction agents (PTAs)- Prussian blue (PB) encapsulated in the core and chemotherapeutic docetaxel (DTX)/ immune adjuvant- imiquimod (R837) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated as “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, which was 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 immune adjuvant R837, the maturation of DCs were promoted. Besides, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving immunosuppressive TME. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased. The 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.