Strategies to prolong drug retention in solid tumors by aggregating Endo-CMC nanoparticles

• DOI: 10.1016/j.jconrel.2023.07.006
• Publication Date: 2023-07-19T14:59:39Z
• Authors: Donglin Xia; Xiaodong Zhang; Huang Hao; Wei Jiang; Chao Chen; Haoming Li; Linzi Feng; Jia Li; Yu Wu; Ling Zhang; Yong Hu
• Keywords: Chitosan; Drug Carriers; Cell Line, Tumor; Humans; Nanoparticles; Antineoplastic Agents; Hydrogels; Nanoparticle Drug Delivery System; 3. Good health

Developing a highly effective nano-drug delivery system with sufficient drug permeability and retention in tumors is still a major challenge for oncotherapy. Herein, a tumor microenvironment responsive, aggregable nanocarriers embedded hydrogel (Endo-CMC@hydrogel) was developed to inhibit the tumoral angiogenesis and hypoxia for enhanced radiotherapy. The antiangiogenic drug (recombinant human endostatin, Endo) loaded carboxymethyl chitosan nanoparticles (Endo-CMC NPs) was wrapped by 3D hydrogel to comprise the Endo-CMC@hydrogel. After peritumoral injection, the Endo-CMC NPs were released, invaded deeply into the solid tumor, and cross-linked with intratumoral calcium ions. The cross-linking process enabled these Endo-CMC NPs to form larger particles, leading to long retention in tumor tissue to minimize premature clearance. This Endo-CMC@hydrogel, integrating the abilities of good tumoral penetration, long retention of anti-drug, and alleviation of hypoxia in tumor tissue, greatly improved the therapeutic effect of radiotherapy. This work provides a proof-of-concept of tumor microenvironment-responding and an aggregable nano-drug delivery system as promising antitumor drug carriers for effective tumor therapy.