**6.2 Biomolecules**

MOFs have proven themselves as effective carriers for the delivery of large biomolecules such as proteins, enzymes, DNA, RNA, and carbohydrates and small biomolecules such as amino acids, peptides and nucleotides [73]. These biomolecule-MOF composites protect the biodegradation of these biomolecules inside physiological systems and offer a pathway for their safe delivery. Many diseases are a result of protein deficiencies in the body. Also, nucleic acid and carbohydrates based therapies are gaining increasing interest. Intracellular delivery of these biomolecules using MOFs will help in preserving their bioactivity and they will be able to reach their targets avoiding unwanted side effects. There are many methods to form biomolecule-MOF composites. Post-synthetic pore entrapment is the most used method, in which biomolecules smaller than the cavity size of MOF directly diffuse into the pores of the MOF. Chen et al. have demonstrated the use of mesoporous NU-1000 MOF for the entrapment of insulin with high loading (approximately 40%) to treat diabetes mellitus (type 2) [74]. Surface attachment/adsorption is another method that is relatively easy, and biomolecules of all sizes can be attached/adsorbed on the surface *via* non-covalent interactions such as hydrogen bonding, π-π interactions, Van-der waals interaction, etc. Ni et al. have reported Hf-DBP NMOF for the delivery of αCD47 antibody attached to its surface [75]. Biomolecules can also be covalently linked to MOFs. Wang et al. immobilized dibenzylooctyne (DBCO) appended DNA on UiO-66-N3 through click reaction between DBCO and azide (N3) group [76]. Co-precipitation or one-pot synthesis is another method for biomolecule-MOF composites. The biomolecule is encapsulated during the synthesis of MOF giving high loading and preventing leakage. Shieh et al. used this *de novo* approach to encapsulate catalase enzyme into the pores of ZIF-90 [77]. Biomimetic mineralization is another *in situ* encapsulation method in which biomolecules act as templates and nucleation sites for the growth of MOF around them, dictating their final size and morphology. Liang et al. demonstrated the use of various protein, enzyme and DNA templates for the synthesis of MOFs by biomimetic mineralization [38]. Bio-MOFs can also be synthesized by incorporating biomolecules into the framework. Biomolecules have reactive functional groups. They can act as organic linkers and react with metal ions to form bio-MOFs. An et al. synthesized bio-MOF-1 made up of zinc-adeninate


## *Drug Carriers*

