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-CMβ [email protected] NPs, RCNP DOX ) and R848-loaded nanoparticles ( [email protected] 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.