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

Zhimeng Chen; Tiantian Wen; Xueyuan Wang; Lin Yang; Zhongjie Wang; Yanru Qin; Yixue Hu; Tianyu Zhang; Dongna Wang; Amin Liu; Liefeng Zhang; Meng Lei; Yongqiang Zhu

doi:10.1016/j.ijbiomac.2022.11.253

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

Int J Biol Macromol. 2023 Jan 31:226:1396-1410. doi: 10.1016/j.ijbiomac.2022.11.253. Epub 2022 Nov 26.

Authors

Zhimeng Chen¹, Tiantian Wen², Xueyuan Wang³, Lin Yang¹, Zhongjie Wang², Yanru Qin², Yixue Hu², Tianyu Zhang², Dongna Wang², Amin Liu¹, Liefeng Zhang⁴, Meng Lei⁵, Yongqiang Zhu⁶

Affiliations

¹ College of Science, Nanjing Forestry University, Nanjing 210037, China.
² School of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China.
³ College of Life Science, Nanjing Normal University, Nanjing 210023, China.
⁴ School of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China. Electronic address: lfzhang@njnu.edu.cn.
⁵ College of Science, Nanjing Forestry University, Nanjing 210037, China. Electronic address: leim@njfu.edu.cn.
⁶ School of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing 210023, China; College of Life Science, Nanjing Normal University, Nanjing 210023, China. Electronic address: 08303@nnu.edu.cn.

PMID: 36442558
DOI: 10.1016/j.ijbiomac.2022.11.253

Abstract

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.

Keywords: Breast cancer; Classified target; DOX; Immunochemotherapy; R848.

MeSH terms

Animals
Apoptosis
Chitosan*
Doxorubicin / pharmacology
Mice
Nanoparticles*
Neoplasms* / drug therapy

Substances

Doxorubicin
Chitosan