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

Abstract

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.

Synergistic applications of cyclodextrin-based systems and metal–organic frameworks in transdermal drug delivery for skin cancer therapy

“…These compounds have gained increasing interest in the last years thanks to their versatility and their wide range of applications, such as catalysis, 93–97 gas capture, 98,99 medical use, 100 and drug delivery. 23,101 For these reasons, a plethora of different MOFs has been synthesized, exploring the properties of different metal centers and ligands and the influence of the reaction conditions (solvent, temperature, pressure, etc. ).…”

“…Due to all the advantages described, MOFs have been extensively studied as drug delivery systems, and many papers and reviews have been published on the topic. 23,92,100,101,114–119 The inclusion of recent advancements in MOF research for wound healing and specific targeting of cancer cells further underscores the potential of MOFs as versatile carriers for drug delivery, opening up new avenues for innovative therapeutic strategies. 111,112 For example, El-Bindary and co-workers have recently reported the preparation of Zr-MOF (synthesized by mixing ZrCl 4 with 2-methylimidazole at basic pH) and ZIF-8 in water and their use to encapsulate doxorubicin.…”

Nanoscale Metal–Organic Frameworks and Nanoscale Coordination Polymers: From Synthesis to Cancer Therapy and Biomedical Imaging

“…Since the initial report of biologically functional NMOFs/NCPs, interest in their biomedical applications has been steadily growing. − NMOFs and NCPs have been explored for a wide range of antitumor therapies, including chemotherapy, phototherapy, chemodynamic therapy (CDT), and combination therapy. , Furthermore, they contribute to achieving efficient imaging techniques including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and optical imaging (OI). ,− Compared to existing nanocarriers, NMOFs/NCPs offer several potential advantages for biomedical applications: (1) the ability to tailor their composition and structure enables the synthesis of NMOFs/NCPs with varying morphologies, sizes, and chemical properties; (2) high specific surface area and unique structures facilitate efficient encapsulation of a diverse spectrum of imaging and therapeutic agents; (3) the capability to modulate stimulus-triggered drug release and biodegradation under specific conditions underscores their potential to enhance biosafety and reduce adverse effects. (4) the utilization of (co)polymers, ligands, proteins, etc., provides the opportunity to design functional coatings that interact with the biological body. − These attributes have been applied in the development of multifunctional NMOFs and NCPs designed to mitigate nonspecific drug dispersion, prolong circulation time, minimize toxicity to normal tissues, enhance treatment effectiveness, and provide theranostic possibilities.…”

Metal-organic frameworks: Drug delivery applications and future prospects

“…Considering their distinctive qualities, including huge porosity, an array of porous designs, huge surface areas extended up to 8000 m 2 g -1 , and customizable frameworks, these materials have attracted significant limelight as an emergent and potential group of porous materials for a variety of applications [ 4 , 5 ]. Considering their numerous benefits and broad applicability, the scientific community has paid a great deal of attention in the past 10 years to the investigation of novel approaches for MOF synthesis [ 6 ]. Essentially, these conjugates are made up of two ingredients: metal ions and organic linkers.…”