Bhasma to Metal Organic Frameworks: A molecular heritage from incineration to innovation

Metallodrugs, incorporates metal ions or metal complexes as active pharmacological agents, are widely used in medicine, especially in therapeutics and medical imaging, since ancient times. These metallodrugs, or metal-containing therapeutic compounds, have gained popularity in recent decades, particularly in the field of cancer treatment. The discovery of cisplatin, a platinum-based chemotherapy drug, demonstrated the potential of metals as potent therapeutic agents having broader application as antiviral, antibacterial, antifungal, anticancer, antiangiogenic, and anti-inflammatory agents.[1,2] The present strategy in metallodrug discovery incorporates clinically approved drugs as coordinating ligands in metal complexes, creating organometallic compounds that address drug resistance and provide alternatives to existing metal-based therapies.[3] The rapid advancement in materials chemistry has spurred extensive research into developing novel micro- or nano-scale platforms for regulated and responsive drug delivery, as well as to optimize therapeutic outcomes while concurrently reducing adverse effects.[4] Metal Organic Frameworks (MOFs) have emerged as a promising option for targeted drug delivery owing to their unique ability to modify configuration and porosity. MOFs present a customizable porous architecture that promotes enhanced drug interactions and facilitates higher drug encapsulation capacities. The therapeutic agents are encapsulated within nanoparticle carriers engineered to shield them from enzymatic and chemical degradation, thereby ensuring precise and targeted delivery to designated sites at predetermined dosages. This innovative technology holds substantial promise for transforming the landscape of drug delivery.[5] METAL ORGANIC FRAMEWORKS (MOFs): A BRIEF OVERVIEW MOFs, which are made up of metal ions or clusters coupled to organic linkers, offer a variety of structural diversity, high porosity, adjustable pore widths, and customizable surface functions. MOFs have emerged as a promising biological material due to their distinct features, which include high surface area, pore volume, variable pore size, flexible functional groups, and drug loading efficiency.[6] MoFs belong to the category of crystalline porous materials, having a wider application including energy storage and conversion, gas separation and storage, water purification, optoelectronics, sensors, medication delivery, etc. They can further be classified as MOFs, Covalent Organic Frameworks, and Polyoxometalates, depending on the atomic joining with covalent bonds/metal ions/clusters.[7] The first MOF, MOF-5, was introduced in the early 1990s with the introduction of tetrahedral [Zn4O]6+ clusters connected by BDC ligands (BDC = 1,4-benzenedicarboxylate).[8,9] This breakthrough marks the beginning of a new era in the science of porous materials, with the development of MOFs, followed by the emergence of an infinite number of MOFs for a variety of applications.[10] MOFs AND BIOMEDICAL RESEARCH Porosity is an important property used in medical implants and tissue scaffolds, and the emergence of MOFs, a relatively young family of porous coordination polymers, has proven popularity in biomedical research in the recent decade, accounting for around 10% of all MOF-related publications. MOFs have proven efficacy with documented biomedical research, particularly in the area of cancer, microbial infections, and inflammatory diseases.[11] MOFs are excellent for encapsulating medications, metals, and gases, protecting sensitive cargo while allowing for controlled, stimuli-responsive release (pH, redox, and temperature). Because of their inherent porosity and the ability to incorporate high-atomic-number metal nodes, MOFs are superior contrast agents used both in imaging and high-sensitivity biosensors. MOFs are increasingly being used in regenerative medicine to improve tissue regeneration in implants and stents. Surface engineering involves coating MOFs (for example, with Polyethylene Glycol [PEG] or lipids) to increase biocompatibility, cellular absorption, and stability in biological fluids.[12,13] MOFs’ surface can be modified using PEG or lipid bilayers to improve their stability, biocompatibility, and cellular absorption in biological fluids. Surface engineering enables functionalization with ligands that specifically target cancer cells, guaranteeing that MOFs deliver their medicament to the site of action while sparing healthy tissues.[14] TRADITIONAL HERBO-MINERAL- METALLIC COMPOUND AND GREEN MOFs Metals have historically served as both therapeutic and toxic agents in medicine. Rasashastra in Ayurveda has long used processed metals such as mercury, gold, and copper, as well as minerals such as HgS, As4S4, PbS, PbO, and others, for medicinal purposes. These metals are subjected to extensive processing procedures or alchemy procedures to change their chemical forms to Bhasma (~calcined ashes), which are suitable forms for therapeutic purposes. The herb-metal interactions help to deliver medications to the target, contribute to therapeutic effects, and reduce toxicity.[15] Bhasma are herbo-metallic ashes in which the metal is calcined alongside other herbal substances to generate organometallic compounds. Metals/minerals are exposed to various purification and incineration processes before being administered internally, with the goal of reducing particle size and transforming them into a biocompatible, bioassimilable, absorbable, and appropriate form for the human body. These nanoparticles are organometallic/organo-mineral complexes because they are merged with biological molecules (of organic liquid media), resulting in better stability, functioning, absorption, assimilation, bioavailability, biocompatibility, component targeting, and efficacy.[16]Bhasma is closer to nanocrystalline materials, which in nanotechnology are solids formed of crystallites smaller than 100 nm in at least one dimension.[17]Swarna bhasma (~calcined gold) is primarily pure gold at the nanoscale, as confirmed by X-Ray Diffraction and Field Emission Transmission Electron Microscopy (TEM) findings. It contains highly crystalline nanostructured gold with spherical gold nanoparticles ranging in size from 5 to 20 nm. Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) results have shown the presence of Au, Si, Ag, Al, Ca, Cu, Fe, K, Mg, etc.[18] Similarly, an analysis of Rajat bhasma (~calcined silver) revealed that it contains nanoparticles of silver (~10–60 nm), uniformly distributed without significant agglomeration. The content of silver measured in Rajat bhasma with ICP-AES was found to be 70.56%.[19] Modern researchers are now synthesizing MOFs with phytoextracts (plant extracts), forming a “green” bridge to the Ayurveda principles of Bhasma production. The biosynthesis method uses plant extract to produce MOFs for biomedical applications in a safe, healthy, and ecologically responsible manner. These environmentally and biologically acceptable MOFs are generated and developed in accordance with specific compositional requirements, which are carefully managed by selecting harmless metal ions and organic linkers as building blocks. Certain plant components, such as stems, roots, buds, leaves, seeds, and rhizomes, have been used to build MOFs and nanoparticles based on the phytochemicals in their extract.[20] Novel nanostructures of Aluminum-based MOF (Al-MOF) samples were created utilizing a green synthesis. For this, Satureja hortensis extract was utilized for the creation of Al-MOF structures, and the Fourier-Transformed Infrared spectra revealed the presence of characteristic bonds. Moreover, the Scanning Electron Microscopy and TEM studies revealed that the sample was composed of multilayers, which were agglomerated but diffused and occurred in spherical particles, indicating the presence of active organic matter, with substantial porosity, suggesting their potential for medical applications. In addition, these Al-MOF samples were treated with varying doses of anticancer agents using the MTT standard method on untreated cancer cells for 24 and 48 h. The result revealed substantial anticancer characteristics, where the Al-MOF exhibited a significantly stronger inhibitory effect on cell proliferation.[21] MOFs have the potential to meet green chemistry standards because, in addition to their surface areas and porous nature, they have exceptional mechanical strength, relatively high thermal stability, and significant resilience in harsh chemical environments. Using plant extracts to construct MOFs is a low-cost, extensible, and ecologically friendly technology. Although, despite their great potential, MOFs face significant limitations regarding long-term toxicity, stability in physiological fluids, and regulatory hurdles for clinical translation. The key challenges include potential metal ion accumulation (e.g. Ag, Cu, and Zn), poor reproducibility in large-scale manufacturing, and the need for complex surface functionalization to ensure biocompatibility.[14] Thus, the journey from Bhasma to MOFs represents a continuum of metallo-pharmaceutical innovation, connecting ancient Ayurvedic practices with cutting-edge nanotechnology, where Bhasma exemplifies early advances in metal-based therapeutics and MOFs represent the future of precision drug delivery systems. However, further scientific research, together with interdisciplinary collaboration, may open the avenues for novel therapeutic procedures which are both effective and holistic. Recognizing and integrating ancient knowledge with modern scientific developments can have a huge impact on the evolution of global healthcare. The link between Bhasma and MOF-like functional activities is mostly inferential, with limited direct experimental confirmation and mechanistic research. The convergence of Ayurvedic herbo-mineral preparations and green MOFs represents a unique intersection of ancient alchemical wisdom and modern nanotechnology. While originating from different eras, both utilize metallic-organic composites to achieve high efficacy, low dosage, and targeted therapeutic outcomes. Modern analytical instruments act as a translation layer, decoding the complex chemical and structural shifts that occur during traditional purification and incineration. By mapping macro-level traditional tests to nanometer-scale data, these tools bridge empirical historical practices with contemporary biomedical validation. Future research should prioritize multidisciplinary techniques that combine Ayurveda, materials science, and nanomedicine to systematically investigate the linkages. Rigorous characterization studies, standardization of Bhasma formulations utilizing modern analytical methods, and comparative studies with synthetic MOFs are required. Furthermore, the development of “green MOFs” based on phytoextracts aligned with Ayurvedic principles represents a promising path; however, warranting further investigation for safer and more sustainable biological applications. The future convergence of Ayurvedic Bhasmas and MOFs hinges on “safety-by-design.” This modern engineering paradigm shifts the focus from managing toxicological risks after synthesis to embedding biocompatibility, environmental safety, and predictability into the very blueprint of the material structure. Finally, well-designed preclinical and clinical research will be critical for validating efficacy, safety, and translational potential, resulting in a scientifically rigorous framework that acknowledges ancient knowledge while promoting modern therapeutics.