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

• Published in: International journal of biological macromolecules 2023-01, Vol.226, p.1396-1410
• Main Authors: Chen, Zhimeng, Wen, Tiantian, Wang, Xueyuan, Yang, Lin, Wang, Zhongjie, Qin, Yanru, Hu, Yixue, Zhang, Tianyu, Wang, Dongna, Liu, Amin, Zhang, Liefeng, Lei, Meng, Zhu, Yongqiang
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Breast cancer; Chitosan; Classified target; DOX; Doxorubicin - pharmacology; Immunochemotherapy; Mice; Nanoparticles; Neoplasms - drug therapy; R848
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.11.253

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, RCNPDOX) and R848-loaded nanoparticles (M2pep-CMCS@R848 NPs, MCNPR848) were prepared. Furthermore, the RCNPDOX and MCNPR848 exhibited good DOX and R848 absorption. Meanwhile, the synergetic cell toxicity of RCNPDOX and MCNPR848 was found. Additionally, RCNPDOX + MCNPR848 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 RCNPDOX + MCNPR848 group could effectively transform the phenotype of tumor-associated macrophages. Importantly, in vivo experiments revealed that RCNPDOX + MCNPR848 NPs exerted excellent anticancer effects in tumor-bearing mice. To summarize, RCNPDOX + MCNPR848 NPs are effective anticancer treatment combining chemotherapy and immunotherapy, M2pep-CMCS and R6RGD-CMβCD are good delivery materials.