Co-delivery of immunochemotherapeutic by classified targeting based on chitosan and cyclodextrin derivatives

Herein, a cyclodextrin derivative (R6RGD-CMβCD) with tumor target and a carboxymethyl chitosan derivative (M2pep-CMCS) with tumor-associated macrophages 2 (TAM2) target were successfully synthesized, respectively. DOX-loaded nanoparticles (R6RGD-CMβCD@DOX NPs, RCNP_DOX) and R848-loaded nanoparticles (M2pep-CMCS@R848 NPs, MCNP_R848) were prepared. Furthermore, the RCNP_DOX and MCNP_R848 exhibited good DOX and R848 absorption. Meanwhile, the synergetic cell toxicity of RCNP_DOX and MCNP_R848 was found. Additionally, RCNP_DOX + MCNP_R848 nanoparticles greatly promoted the expression levels of cleaved Caspase3, which indicated that the nanoparticles could induce cell apoptosis. At the same time, the immunohistochemical images exhibited that RCNP_DOX + MCNP_R848 group could effectively transform the phenotype of tumor-associated macrophages. Importantly, in vivo experiments revealed that RCNP_DOX + MCNP_R848 NPs exerted excellent anticancer effects in tumor-bearing mice. To summarize, RCNP_DOX + MCNP_R848 NPs are effective anticancer treatment combining chemotherapy and immunotherapy, M2pep-CMCS and R6RGD-CMβCD are good delivery materials.