Development of new diagnostic tools are important to accomplish therapeutic efficacies in treating the infectious disease and the next generation smart probes are required to be both therapeutics and diagnostics together (theranostics) in single system so that maximize impact in their biomedical applications. Fluorescent-tagged biodegradable cationic aliphatic polyesters are excellent candidates for this purpose to directly visualize the action of the polymer by imaging techniques as well as quantify their antimicrobial activity in real-time. We have recently developed water soluble cationic polycaprolactones by ring opening polymerisation and they were successfully tested for their antibacterial activity in gram-negative bacterium Escherichia coli. The polymers showed non-hemolytic nature in mice red blood cells (RBCs) and non-toxic trend in wild type mouse embryonic fibroblast (MEF) cells with a selectivity index of &gt; 104. Encapsulation of an anionic biomarker, HPTS (8-hydroxypyrene -1, 3, 6-trisulfonic acid) in the cationic PCL nano-assemblies resulted in the formulation of theranostic nanoprobe to visualize live and dead bacteria distinctly during the course of antibacterial activity. Recently this PCL nano-probe design has been improved by conjugating TPE-chromophores to exploit its action of aggregation induced emission (AIE) to study the membrane disruption mechanism in-depth. TPE-based macro initiator was designed and developed to make TPE-PCL fluorescent block and random copolymers. These polymers showed excellent aqueous stability with highly blue-fluorescent characteristics and enabled the direct visualization of their binding on the bacterial membrane. Confocal microscopic analysis in E. coli has established that membrane pore is created by the action of polymer at both inner and outer membranes. Time-dependent antimicrobial activity revealed that polymers minimum required 2 hrs in order to act on the bacterial membrane to accomplish &gt; 98 % growth inhibition. Currently efforts are taken to expand the structural engineering aspects to study the role of the polymer 3D architectures and also biofilm inhibition.

Biodegradable polymeric fluorescent nano-assemblies for direct visualization and quantification of antimicrobial activity

ACS Spring Meeting 2021

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