Smart hydrogels for overcoming cancer multidrug resistance

Area of Science:

• Oncology
• Nanomedicine
• Biomaterials

Background:

• Multidrug resistance (MDR) is a major obstacle in cancer treatment.
• Current nanomedicines face challenges with tumor microenvironment (TME) delivery and heterogeneity.
• Passive drug delivery strategies are insufficient for overcoming MDR.

Purpose of the Study:

• To review strategies for overcoming MDR by active TME remodeling.
• To highlight the potential of next-generation injectable hydrogels in cancer therapy.
• To explore the integration of mechanobiology, immunometabolism, and AI for enhanced oncology treatments.

Main Methods:

• Utilizing injectable hydrogels for localized TME modulation.
• Applying principles of mechanobiology to soften the extracellular matrix and decouple YAP/TAZ signaling.
• Disrupting tumor hypoxia-driven bioenergetics and enhancing drug delivery.
• Leveraging nanogel trafficking to bypass intracellular drug sequestration and efflux pumps.
• Mobilizing antitumor immunity via in situ vaccination and myeloid cell reprogramming.
• Integrating artificial intelligence (AI) and patient-derived organoids for treatment optimization.

Main Results:

• Hydrogels can create viscoelastic niches for controlled drug retention and TME modulation.
• Biomechanical softening of the TME disrupts YAP/TAZ-mediated mechanotransduction.
• Metabolic disruption targets hypoxia-driven cancer cell bioenergetics.
• Nanogel systems facilitate payload delivery, overcoming intracellular resistance mechanisms.
• Immune cell reprogramming and in situ vaccination enhance antitumor responses.
• AI and organoid models offer a pathway for clinical translation.

Conclusions:

• Active, localized TME remodeling using advanced hydrogels offers a promising strategy against MDR.
• This multi-tiered approach integrates biomechanics, immunometabolism, and nanomedicine for synergistic effects.
• AI and patient-derived organoids are crucial for bridging laboratory research and clinical application in oncology.