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

Scientific fraternity revealed thepotential of stimuli-responsivenanotherapeutics for cancer treatment that aids in tackling the majorrestrictions of traditionally reported drug delivery systems. Amongstimuli-responsive inorganic nanomaterials, metal-organic frameworks(MOFs) have transpired as unique porous materials displaying resilientstructures 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-responsivemultifunctional MOFs for targeted drug delivery and bioimaging foreffective cancer therapy. Initially, the concept of cancer, traditionalcancer treatment, background of MOFs, and approaches for MOFs synthesishave been discussed. After this, applications of stimuli-responsivemultifunctional MOFs-assisted nanostructures that include pH, light,ions, temperature, magnetic, redox, ATP, and others for targeted drugdelivery and bioimaging in cancer have been thoroughly discussed.As an outcome, the designed multifunctional MOFs showed an alterationin properties due to the exogenous and endogenous stimuli that arebeneficial for drug release and bioimaging. The several reported typesof stimuli-responsive surface-modified MOFs revealed good biocompatibilityto normal cells, promising drug loading capability, target-specificdelivery of anticancer drugs into cancerous cells, etc. Despite substantialprogress in this field, certain crucial issues need to be addressedto reap the clinical benefits of multifunctional MOFs. Specifically,the toxicological compatibility and biodegradability of the buildingblocks of MOFs demand a thorough evaluation. Moreover, the investigationof sustainable and greener synthesis methods is of the utmost importance.Also, the low flexibility, off-target accumulation, and compromisedpharmacokinetic profile of stimuli-responsive MOFs have attractedkeen attention. In conclusion, the surface-modified nanosized designof inorganic diverse stimuli-sensitive MOFs demonstrated great potentialfor targeted drug delivery and bioimaging in different kinds of cancers.In the future, the preference for stimuli-triggered MOFs will opena new frontier for cancer theranostic applications.