1. Academic Validation
  2. Chitosan-based hybrid nanospheres for vessel normalization towards enhancing tumor chemotherapy

Chitosan-based hybrid nanospheres for vessel normalization towards enhancing tumor chemotherapy

  • Int J Biol Macromol. 2024 May;267(Pt 1):131409. doi: 10.1016/j.ijbiomac.2024.131409.
Ding Wang 1 Yaoqing Chu 1 Shuiping Liu 2 Lianjiang Tan 3
Affiliations

Affiliations

  • 1 School of Materials Science and Engineering, Shanghai Institute of Technology, Shanghai 201418, China.
  • 2 College of Textile and Clothing, Yancheng Institute of Technology, Yancheng 224051, China.
  • 3 School of Materials Science and Engineering, Shanghai Institute of Technology, Shanghai 201418, China. Electronic address: tanlianjiang@126.com.
Abstract

Vessel normalization has proved imperative in tumor growth inhibition. In this work, biopolymer-based hybrid nanospheres capable of normalizing blood vessels were designed to improve the therapeutic effect of chemotherapeutic drugs. Zn0.4Fe2.6O4 nanoparticles (ZFO NPs) were synthesized, and were encapsulated in cross-inked chitosan (CS) along with a nitric oxide (NO) precursor, DETA NONOate, forming hybrid ZFO/NO@CS nanospheres highly stable in physiological environment. The structure, morphology and size of the nanospheres were characterized. The ZFO/NO@CS nanospheres could release NO under acidic conditions typical of intratumoral and intracellular environment. The results of related factors expression, wound healing and tube formation assays demonstrated that both the encapsulated ZFO NPs and the released NO were able to inhibit angiogenesis in tumors. The ZFO/NO@CS nanospheres enhanced the antitumor efficacy of the chemotherapeutic drug DOX by normalizing tumor vessels, as evidenced by in vivo experiments for CT26 tumor-bearing mice. By analyzing the contents of Fe in the tumor and different organs, the nanospheres were found to accumulate primarily at the tumor site. The blood analysis showed little side effect of the nanospheres. The ZFO/NO@CS nanospheres have great potential in improving tumor therapeutic effect when used in combination with chemotherapeutic drugs.

Keywords

Chitosan-based nanospheres; Nitric oxide; Tumor chemotherapy; Vessel normalization; ZFO nanoparticles.

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