Biodegradable Polymer Theranostic Fluorescent Nanoprobe for Direct Visualization and Quantitative Determination of Antimicrobial Activity

Abstract

We report a biodegradable fluorescent theranostic nanoprobe design strategy for simultaneous visualization and quantitative determination of antibacterial activity for the treatment of bacterial infections. Cationic-charged polycaprolactone (PCL) was tailor-made through ring-opening polymerization methodology, and it was self-assembled into well-defined tiny 5.0 ± 0.1 nm aqueous nanoparticles (NPs) having a zeta potential of +45 mV. Excellent bactericidal activity at 10.0 ng/mL concentration was accomplished in Gram-negative bacterium Escherichia coli (E. coli) while maintaining their nonhemolytic nature in mice red blood cells (RBC) and their nontoxic trend in wild-type mouse embryonic fibroblast cells with a selectivity index of >10 4 . Electron microscopic studies are evident of the E. coli membrane disruption mechanism by the cationic NP with respect to their high selectivity for antibacterial activity. Anionic biomarker 8-hydroxy-pyrene-1,3,6-trisulfonic acid (HPTS) was loaded in the cationic PCL NP via electrostatic interaction to yield a new fluorescent theranostic nanoprobe to accomplish both therapeutics and diagnostics together in a single nanosystem. The theranostic NP was readily degradable by a bacteria-secreted lipase enzyme as well as by lysosomal esterase enzymes at the intracellular compartments in <12 h and support their suitability for biomedical application. In the absence of bactericidal activity, the theranostic nanoprobe functions exclusively as a biomarker to exhibit strong greenfluorescent signals in live E. coli. Once it became active, the theranostic probe induces membrane disruption on E. coli, which enabled the costaining of nuclei by red fluorescent propidium iodide. As a result, live and dead bacteria could be visualized via green and orange signals (merging of red+green), respectively, during the course of the antibacterial activity by the theranostic probe. This has enabled the development of a new image-based fluorescence assay to directly visualize and quantitatively estimate the real-time antibacterial activity. Time-dependent bactericidal activity was coupled with selective photoexcitation in a confocal microscope to demonstrate the proof-of-concept of the working principle of a theranostic probe in E. coli. This new theranostic nanoprobe creates a new platform for the simultaneous probing and treating of bacterial infections in a single nanodesign, which is very useful for a longterm impact in healthcare applications.

Dielectric Properties of ZnO-Based Nanocomposites and Their Potential Applications

“…Biodegradable polymers nanocomposites are doing very well in various fields. ey are used for food packaging to improve the shelf life of food [191][192][193], as a photocatalyst to purify water [194,195], cancer treatments [196][197][198], drug delivery in the medical field [199][200][201], antimicrobial activities [202][203][204], tissue engineering [205], and sensors [206,207].…”

Structural Engineering of Star Block Biodegradable Polymer Unimolecular Micelles for Drug Delivery in Cancer Cells

“…This emphasized the need for developing new unimolecular micelle nanoassemblies in a fully biodegradable polymer platform that would open a new avenue of opportunities in cancer research. For the past decade, our research group has been exploring carboxylic functionalized PCL-based di- and triblock copolymers for delivering a cocktail of DOX and cisplatin for synergistic combination therapy in breast cancer cell lines. ,− Fluorescent labeled PCL block copolymers were also developed to study the intracellular enzymatic-biodegradation aspects of the PCL backbone by the FRET mechanism. − Biodegradable cationic PCL nanoassemblies were also made, and their fluorescent-cum-antimicrobial action was studied in detail in Escherichia coli . This experience helped us to design one of the first examples of fully biodegradable star block copolymers based on a hydrophobic PCL core and a carboxylic acid-substituted hydrophilic PCL shell as shown in Figure .…”

Star-Polymer Unimolecular Micelles for Brain Specific Delivery of Anticancer Drug

“…Tweaking the topology of the macromolecular architectures was found to be very crucial factor in designing the star-UMM. For this purpose, hydrophobic polycaprolactone (PCL) and carboxylic substituted hydrophilic PCL segments were chosen based on our expertise in cancer research [44][45][46][47][48][49][50][51][52][53] and systematically several structures such as linear di-blocks, star di-blocks, and star random copolymers were tailor-made by ring opening polymerization (ROP) to get the right polymer geometry with high encapsulation capabilities. The in vivo biodistribution data established the supremacy of the star-UMM platform for crossing the BBB with reduced side-effect of cardiotoxicity.…”