In situ forming hydrogels for colorectal cancer therapy

Area of Science:

• Biomaterials Science
• Cancer Therapy
• Drug Delivery Systems

Background:

• Systemic treatments for colorectal cancer (CRC) face challenges like off-target toxicity and poor drug accumulation.
• In situ forming hydrogels (ISFGs) provide a localized drug delivery platform to overcome these limitations.
• ISFGs form drug depots in the tumor microenvironment or surgical bed via stimuli-responsive sol-gel transitions.

Purpose of the Study:

• To review recent advancements in ISFG materials for CRC therapy.
• To highlight the therapeutic applications and preclinical efficacy of ISFGs in CRC.
• To discuss the translational potential and future directions of ISFGs in CRC treatment.

Main Methods:

• Review of literature on ISFG materials (thermosensitive, ion-responsive, dynamic networks, ROS/pH-sensitive polymers).
• Analysis of ISFG drug delivery strategies for cytotoxic agents, immunomodulators, photosensitizers, and metabolic inhibitors.
• Evaluation of preclinical data on ISFG efficacy, biocompatibility, and clinical translation status.

Main Results:

• ISFGs demonstrate injectability, adhesiveness, and biocompatibility.
• Engineered ISFGs enable synergistic chemo-immunotherapy, postoperative vaccines, and tumor microenvironment remodeling.
• Preclinical studies show enhanced antitumor efficacy, reduced recurrence, immune activation, abscopal effects, and minimal systemic toxicity.

Conclusions:

• ISFGs combine localized treatment with systemic immune priming, ideal for neoadjuvant, adjuvant, or interventional CRC therapy.
• Clinical translation is progressing, with ISFG systems entering early-phase trials.
• ISFGs represent a versatile strategy for improving local tumor control and long-term outcomes in colorectal cancer.