Exoskeleton for Biofunctionality Protection of Enzymes and Proteins for Intracellular Delivery

Abstract

Driven by the challenges to protect and restore biofunctionality of enzymes and proteins due to fluctuation of temperature, pH, and solvents, desired tolerances against the intracellular microenvironment can be gained via sheltering enzyme and proteins into nanoscale cages of exoskeleton, one of which involves confinement into the pore and channels of metal–organic frameworks (MOFs). While confining biomolecules, such framework exoskeleton and nanoscale cages should drive the enzyme embedding process and induce the formation of the resulting biocomposite suitable for intracellular delivery for therapeutic applications. Translational challenges faced by framework materials such as ZIF‐8 exoskeleton along with few more MOFs for armoring biofunctionality modulation of enzymes and proteins for intracellular delivery efficiency are highlighted. Herein, enzyme embedding patterns, encapsulation of oxidase enzymes, hybrid protein–MOFs, protected protein delivery, and mechanism of biofunctionality protection are discussed. Furthermore, an attempt is made to highlight the scope of exoskeleton biocomposites.

Biomolecules meet organic frameworks: from synthesis strategies to diverse applications

“…67,68 Polysaccharides with relatively rigid ring structures not only guaranteed the mechanical strength but also made resultant organic framework permeant porosity. 69,70 Among them, BOFs based on cyclodextrins (CD) are the most widely used polysaccharide-BOFs because of their inherent cavities (17 Å generated by CD) and the existence of a lot of hydroxyl groups. 71 These make them promising candidates for the adsorption and separation applications of diversified gases and other organic small molecules.…”

Biocompatible nanoreactors of catalase and nanozymes for anticancer therapeutics

“…Therefore, this strategy generates a scope encapsulating IrO x within a protein or MOF‐based exoskeleton for the protection of tumor‐therapy strategy. [ 81,82 ] At the mildly acidic TME, IrO x ‐GOD can catalyze H 2 O 2 to O 2 production for resisting tumor hypoxia, and correspondingly O 2 can further react with glucose to produce gluconic acid and H 2 O 2 . This occurs by the cyclic consumption of glucose and generation of O 2 and H 2 O 2 .…”

Cellular metabolic activity and electrochemical stability assay of embedded oxidoreductase enzyme confined in the nanospace of a framework exoskeleton

“…3 The ZIF framework is particularly versatile for encapsulating and protecting biomolecules, including proteins, enzymes, and stem cells, for immunotherapy via intracellular delivery for anticancer therapeutics. [10][11][12] The overproduction of reactive oxygen species (ROS) can cause oxidative stress in cells and tissues, for which the simultaneous encapsulation of multiple enzymes, such as the two kinds of antioxidants superoxide dismutase (SOD) and catalase (CAT), can maintain redox homeostasis. 13 Such MOF-biomolecule heterostructures introduces multiple components into one MOF encapsulation unit and is seen as a promising approach to design all-in-one theranostics.…”