Multi-functional carboxymethyl chitin-based nanoparticles for modulation of tumor-associated macrophage polarity

Yunfeng Wan; Wenjie Yu; Jiami Li; Na Peng; Xiao Ding; Yanlong Wang; Tao Zou; Yang Cheng; Yi Liu

doi:10.1016/j.carbpol.2021.118245

Multi-functional carboxymethyl chitin-based nanoparticles for modulation of tumor-associated macrophage polarity

Carbohydr Polym. 2021 Sep 1:267:118245. doi: 10.1016/j.carbpol.2021.118245. Epub 2021 May 24.

Authors

Yunfeng Wan¹, Wenjie Yu¹, Jiami Li², Na Peng³, Xiao Ding¹, Yanlong Wang¹, Tao Zou¹, Yang Cheng¹, Yi Liu⁴

Affiliations

¹ Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China.
² College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China.
³ Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China. Electronic address: pengna@wust.edu.cn.
⁴ Key Laboratory of Coal Conversion and New Carbon Materials of Hubei Province, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China; State Key Laboratory of Separation Membranes and Membrane Process, School and Chemical Engineering & School of Environmental Science and Engineering, Tiangong University, Tianjin 300378, China; College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China. Electronic address: yiliuchem@whu.edu.cn.

PMID: 34119189
DOI: 10.1016/j.carbpol.2021.118245

Abstract

Current challenge of using cytokines is its poor distribution and systemic side effects. To avoid this issue, we prepared the tumor-targeted and microenvironment-responsive nanocarriers (TRN), which were consisted of α-tocopheryl succinate (α-TOS) loaded mesoporous silica nanoparticles as cores, and surface-modified by thioketal-linkage, electrostatically coated with carboxymethyl chitin, and further anchored glucose-regulated protein 78-binding peptide as shells for encapsulating IL-12. TRN showed a size of 260 nm after encapsulated IL-12 and α-TOS with loading content of 0.0206% and 7.21%, respectively, and exhibited good biocompatibility to 4 T1 cells and macrophages. Moreover, IL-12/α-TOS loaded TRN displayed obvious anti-tumor efficacy on BALB/c nude mice bearing 4 T1 tumors, which was derived from promoted targeting to tumor tissue, endocytosed by macrophages and locally release IL-12 to subsequently repolarize tumor-associated macrophages into tumoricidal M1 phenotype with reduced side effects. The nanosystem exhibited as a promising strategy with functional conversion of macrophages in tumor microenvironment for anti-tumor therapy.

Keywords: Carboxymethyl chitin; Endocytosed; Microenvironment-responsive; TAM repolarization; Tumor-targeted.

MeSH terms

Animals
Antineoplastic Agents / therapeutic use*
Cell Line, Tumor
Cell Polarity / drug effects*
Chitin / analogs & derivatives
Chitin / chemistry
Chitin / toxicity
Drug Carriers / chemistry*
Drug Carriers / toxicity
Immunotherapy
Interleukin-12 / therapeutic use
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles / chemistry*
Nanoparticles / toxicity
Neoplasms / drug therapy*
RAW 264.7 Cells
Silicon Dioxide / chemistry
Silicon Dioxide / toxicity
Tumor-Associated Macrophages / drug effects*
alpha-Tocopherol / therapeutic use

Substances

Antineoplastic Agents
Drug Carriers
Chitin
Interleukin-12
O-(carboxymethyl)chitin
Silicon Dioxide
alpha-Tocopherol