Implantable Bioresponsive Hydrogel Prevents Local Recurrence of Breast Cancer by Enhancing Radiosensitivity

Abstract

Breast cancer is one of the most common types of cancer. Patients are often concerned about regional recurrence after breast cancer surgery. Radiotherapy plays a vital role in reducing recurrence and prolonging the survival of patients undergoing breast-conserving surgery and high-risk mastectomy. However, 8–15% of patients still have disease progression due to radiation resistance. Therefore, new strategies for combination radiotherapy sensitization must be investigated. In this study, an implantable drug loading system, sunitinib nanoparticles @ matrix metalloproteinases -response hydrogel (NSMRH), uses enzyme-sensitive hydrogel as a carrier to load sunitinib nanoparticles, was identified. The releasing profile demonstrated that sunitinib nanoparticles may be continuously released from the hydrogels. Functional experiments revealed that, when paired with NSMRH, radiation may significantly inhibit tumor cell proliferation, migration, and invasion in vitro. Further animal experiments showed that NSMRH combined with radiotherapy could more effectively control the recurrence of subcutaneous xenograft tumors, prolong the survival time, and have no obvious toxicity in nude mice. Finally, by studying the molecular mechanism of NSMRH, it was hypothesized that in breast cancer cells, NSMRH cooperated with sensitized radiotherapy, mainly due to significantly blocking the G2/M phase, reducing the DNA repair efficiency, inhibiting tumor angiogenesis, promoting apoptosis, and reversing the abnormal expression of platelet-derived growth factor receptor alpha (PDGFRA) after radiotherapy. These findings suggest that NSMRH’s radiation sensitization and anti-tumor activity may aid in the development of a novel method in future clinical applications.

In-vivo studies of targeted and localized cancer drug release from microporous poly-di-methyl-siloxane (PDMS) devices for the treatment of triple negative breast cancer

“…The CS-FA-MBZ implants effectively inhibited the growth and spread of 4T1 breast tumors 80 . Another study has identified an implantable drug loading system for sunitinib nanoparticles at matrix metalloproteinases-response hydrogel (NSMRH), which uses enzyme-sensitive hydrogel as a carrier to load sunitinib nanoparticles 81 . Animal experiments showed that NSMRH combined with radiotherapy could more effectively control the recurrence of subcutaneous xenograft tumors, prolong the survival time, and have no obvious toxicity in nude mice.…”

Hydrogel systems for targeted cancer therapy

“…In addition, the hydrogel can effectively carry radiosensitizers, Chemotherapeutic drugs, photosensitizers and heat-sensitive agents simultaneously. Therefore, the hydrogel systems can not only inhibit the self-replication and random repair of damaged DNA but also effectively alleviate the radiation resistance state of the cancer under hypoxia, which leads to multiple damages to DNA function and enhances the therapeutic effect of brachytherapy ( Chen et al, 2021a ; Fu et al, 2022 ). Wang et al (2021) developed an injectable hydrogel based on Endostatin (ES) and hyaluronic acid-tyramine.…”

Recent progress of hydrogel-based local drug delivery systems for postoperative radiotherapy

“…Fu et al. introduced a matrix metalloproteinase (MMP) -responsive hydrogel loaded with sunitinib nanoparticles (NS-MRH) to improve radiosensitivity and prevent local breast cancer recurrence ( 75 ). By being injected into the postoperative cavity and continuously releasing sunitinib, the constructed hydrogel system in this study successfully sensitized radiation and inhibited tumor recurrence.…”