Stimuli-Responsive Design of Metal-Organic Frameworks for Cancer Theranostics: Current Challenges and Future Perspective.

Scientific fraternity revealed the potential of stimuli-responsive nanotherapeutics for cancer treatment that aids in tackling the major restrictions of traditionally reported drug delivery systems. Among stimuli-responsive inorganic nanomaterials, metal-organic frameworks (MOFs) have transpired as unique porous materials displaying resilient structures and diverse applications in cancer theranostics. Mainly, it demonstrates tailorable porosity, versatile chemical configuration, tunable size and shape, and feasible surface functionalization, etc. The present review provides insights into the design of stimuli-responsive multifunctional MOFs for targeted drug delivery and bioimaging for effective cancer therapy. Initially, the concept of cancer, traditional cancer treatment, background of MOFs, and approaches for MOFs synthesis have been discussed. After this, applications of stimuli-responsive multifunctional MOFs-assisted nanostructures that include pH, light, ions, temperature, magnetic, redox, ATP, and others for targeted drug delivery and bioimaging in cancer have been thoroughly discussed. As an outcome, the designed multifunctional MOFs showed an alteration in properties due to the exogenous and endogenous stimuli that are beneficial for drug release and bioimaging. The several reported types of stimuli-responsive surface-modified MOFs revealed good biocompatibility to normal cells, promising drug loading capability, target-specific delivery of anticancer drugs into cancerous cells, etc. Despite substantial progress in this field, certain crucial issues need to be addressed to reap the clinical benefits of multifunctional MOFs. Specifically, the toxicological compatibility and biodegradability of the building blocks of MOFs demand a thorough evaluation. Moreover, the investigation of sustainable and greener synthesis methods is of the utmost importance. Also, the low flexibility, off-target accumulation, and compromised pharmacokinetic profile of stimuli-responsive MOFs have attracted keen attention. In conclusion, the surface-modified nanosized design of inorganic diverse stimuli-sensitive MOFs demonstrated great potential for targeted drug delivery and bioimaging in different kinds of cancers. In the future, the preference for stimuli-triggered MOFs will open a new frontier for cancer theranostic applications.