Multifunctional stimuli-responsive hybrid nanogels for cancer therapy: Current status and challenges

With cancer research shifting focus to achieving multifunctionality in cancer treatment strategies, hybrid nanogels are making a rapid rise to the spotlight as novel, multifunctional, stimuli-responsive, and biocompatible cancer therapeutic strategies. They can possess cancer cell-specific cytotoxic effects themselves, carry drugs or enzymes that can produce cytotoxic effects, improve imaging modalities, and target tumor cells over normal cells. Hybrid nanogels bring together a wide range of desirable properties for cancer treatment such as stimuli -responsiveness, efficient loading and protection of molecules such as drugs or enzymes, and effective crossing of cellular barriers among other properties. Despite their promising abilities, hybrid nanogels are still far from being used in the clinic, and their available data remains relatively limited. However, many studies can be done to facilitate this clinical transition. This review is critically summarizing and analyzing the recent information and progress on the use of hybrid nanogels particularly inorganic nanoparticle-based and organic nanoparticle-based hybrid nanogels in the field of oncology and future directions to aid in transferring those results to the clinic. This work concludes that the future of hybrid nanogels is greatly impacted by therapeutic and non-therapeutic factors. Therapeutic factors include the lack of hemocompatibility studies, acute and chronic toxicological studies, and information on agglomeration capability and extent, tumor heterogeneity, interaction with proteins in physio-logical fluids, endocytosis-exocytosis, and toxicity of the nanogels' breakdown products. Non-therapeutic factors include the lack of clear regulatory guidelines and standardized assays, limitations of animal models, and dif-ficulties associated with good manufacture practices (GMP).

Automated summary

Hybrid nanogels are emerging as novel and multifunctional cancer therapeutic strategies, with the potential to possess cytotoxic effects, carry drugs/enzymes, improve imaging, and target tumor cells. Despite their promising abilities, their clinical application is limited and further research is needed. Factors affecting their future include lack of hemocompatibility studies, toxicological evaluations, and information on tumor heterogeneity and interaction with physiological fluids.