In recent decades, polymeric materials have been extensively investigated for their widespread therapeutic applications in various biomedical fields. In particular, biomolecule conjugated polymers continue to draw attention due to their distinctive physicochemical and biological properties. By appending biomolecules on polymeric constructs, these synthetic macromolecules can be strategized as multimotive theranostic agents. In this Review, we intend to spotlight the biomedical applications of polymeric materials containing cholic acid (CA) as the biomolecular counterpart. CA is the most abundantly produced bile acid during cholesterol metabolism in the human body and is also the least expensive one. The fascinating properties such as inimitable facial amphiphilicity, convenient bioavailability, trivial cytotoxicity, and excellent biocompatibility make CA unique to design numerous cholic acid-based polymers (CAPs) in the diverse areas of biomedical research. The primary focus of this Review is to highlight the recent achievements (2011−present) on the obligatory role of the CA moiety in CAPs in these biomedical applications. Especially the therapeutic applications which include drug delivery, gene transfection, antimicrobial activity, bioimaging and diagnosis, wound healing, and other miscellaneous bioapplications are highlighted in this Review.

A family of amphiphilic copolymers containing hydrophobic cholate pendants has been prepared by copolymerization of cholic acid-based monomer 2-(methacryloxy)-ethyl cholate (MAECA) with polyethylene glycol methyl ether methacrylate (PEGMA). The polymers differ for the content of MAECA that increases from 0 to 35%. The copolymers partition within liposomes and display potent ionophoric activity forming large pores in the membrane and allowing the leakage of small inorganic ions (H + , Na + ) and of large polar organic molecules (calcein). Their activity is strictly correlated to the content of cholic acid subunits, increasing as the fraction of cholate moiety increases.

The design and synthesis of a multifunctional macromolecular architecture featuring alternating cholic acid (CA) and glucose pendants in a polymer side-chain is reported. The target architecture was prepared by reversible addition–fragmentation chain-transfer copolymerization of styrene-conjugated CA (the bitter monomer) and acetyl-protected glucose appended maleimide (the sweet monomer) using the polyethylene glycol-conjugated chain transfer agent. Removal of the acetates resulted in amphiphilic “bitter-sweet” alternating copolymers that were self-assembled in aqueous media having CA containing bitter core and sugar-coated sweet shell. Dynamic light scattering measurements in water, field emission scanning electron microscopy, and transmission electron microscopy confirmed the formation of 40 to 75 nm sized micellar nanoscaffolds, depending on the chain-length of the copolymers. The nanoparticles successfully encapsulated hydrophobic molecules as witnessed via fluorescence spectroscopy using Nile red as an exemplary guest. Interestingly, the alternating copolymer recognized β-cyclodextrin (β-CD) through the formation of inclusion complexes with lateral cholate moieties in the polymer as evident from 2D NMR and nuclear Overhauser effect experiments. It is worth noting that the polymer and its inclusion complex were found to be capable of recognizing Concanavalin A (Con A), as shown by turbidimetric assay and isothermal titration calorimetry. Interestingly, the inclusion complex of the alternating copolymer showed significantly higher autofluorescence in the presence of Con A with respect to that of un-complexed one. Thus, the present study offers a simple way to prepare a multifunctional alternating copolymer having hydrophobic molecule encapsulation, inherent fluorescence, inclusion complex formation with β-CD, and lectin recognition capabilities.

To understand the effect of cholic acid (CA)-based charge variable polymeric architectures on modulating the insulin aggregation process, herein, we have designed side-chain cholate-containing charge variable polymers. Three different types of copolymers from 2-(methacryloyloxy)ethyl cholate with anionic or cationic or neutral units have been synthesized by reversible addition-fragmentation chain transfer polymerization. The effects of these copolymers on the insulin fibrillation process was studied by multiple biophysical approaches including different types of spectroscopic and microscopic analyses. Interestingly, the CA-based cationic polymer (CP-10) was observed to inhibit the insulin fibrillation process in a dose-dependent manner and to act as an effective anti-amyloidogenic agent. Corresponding anionic (AP-10) and neutral (NP-10) copolymers with cholate pendants remained insignificant in controlling the aggregation process. Tyrosine fluorescence assays and Nile red fluorescence measurements demonstrate the role of hydrophobic interaction to explain the inhibitory potencies of CP-10. Furthermore, circular dichroism spectroscopic measurements were carried out to explore the secondary structural changes of insulin fibrils in the presence of cationic polymers with and without cholate moieties. Isothermal titration calorimetry measurements revealed the involvement of electrostatic polar interaction between the CA-based cationic polymer and insulin at different stages of fibrillation. Overall, this work demonstrates the efficacy of the CA-based cationic polymer in controlling the insulin aggregation process and provides a novel dimension to the studies on protein aggregation.

Cytoskeletal movement is a compulsory necessity for proper cell functioning and is largely controlled by actin filament dynamics. The actin dynamics can be finetuned by various natural and artificial materials...