Injectable halloysite-g-chitosan hydrogels as drug carriers to inhibit breast cancer recurrence

Abstract

Breast cancer is one of the frequently occurring malignant tumors in the world. Breast resection, high tumor recurrence rate and high dose chemotherapy cause great pain to patients. Is there a way to prevent tumor recurrence efficiently while promoting new tissue generation after tumor resection? Based on this, an injectable biocompatible thiolated chitosan (CSSH) hydrogel with pH-response was designed to be used for accurate treatment of tumor cells in the initial stage of tissue resection and for tissue reconstruction later. To improve the mechanical strength of hydrogels, reduce the toxic and side effects, and delay the release of doxorubicin (DOX), halloysite nanotubes (HNTs) were modified to obtain thiolated HNTs (HNTs-SH), then loaded DOX (DOX@HNTs-SH), and further cross-linked CSSH to form DOX@CSSH/HNTs-SH Gel. The results showed that HNTs-SH can be evenly dispersed in the gel matrix, which improve the compressive strength of the hydrogels. In vitro DOX release experiments showed that the hydrogels were pH sensitive, DOX released slowly at normal physiological pH, but released quickly in the acidic microenvironment of tumors. Cell experiments showed that DOX@CSSH/HNTs-SH Gel released DOX can be taken up by MCF-7, thereby effectively inhibited its growth. In vivo recurrence experiments showed that the carriers can reduce the toxic and side effects of DOX, and effectively inhibited the recurrence and repair the defect tissue after tumor resection. Therefore, the drug-loaded gel is expected to be used as a carrier for local accurate and effective drug release, especially for inhibiting recurrence and repairing defective tissues after tumor resection.