Polymersomes are a unique class of self-assembled nano-scaffolds. They have very well-defined compartmentalization of hydrophilic core and hydrophobic layer for loading both water-soluble and insoluble cargoes, respectively. Incorporating fluorophore in polymersomes is an elegant approach for developing theranostic nanoprobes to study their real-time drug delivery aspects. We have recently developed a new <i>fluorescent polysaccharide polymersome</i> by cleverly merging the aggregation-induced emission (AIE) concept in clinically important polysaccharide-dextran. For this purpose, plant-based hydrophobic unit 3-pentadecyl phenol (from cashew nut shell liquid) was employed as vesicular directing hydrophobic component and tetraphenylethylene (TPE) as AIE-chromophores. This tailor-made AIE-driven polymersome was employed as a FRET donor along with acceptor-fluorophores such as Rose Bengal and Nile red (as FRET acceptor) to engineer a <i>smart enzyme-responsive fluorescent polysaccharide polymersome FRET nanoprobes</i> for cancer research. The TPE chromophore's selective photoexcitation enabled the FRET process between TPE donor and RB (or NR) acceptor molecule in &lt; 50 Å Forster distance, which could be afforded by the polymersome nano-assemblies. In vitro release studies confirmed that the polymersome FRET probe was stable at the extracellular condition. It underwent lysosomal esterase enzymatic-biodegradation at the intracellular compartments to release the cargoes. In vitro cytotoxicity studies established that the fluorescent polymersome probe was non-toxic to cells up to 300 mg/mL. Live-cell confocal microscope imaging was deployed to visualize and quantify the enzyme-trigger function of FRET probes directly. These probes became functional upon exposure to the lysosomal enzyme at the intracellular compartments. The FRET emission assay established that the polymersome typically required 2 h for the enzymatic-disassembly at the intracellular conditions. The custom-designed fluorescent polysaccharide polymersomes are a new entry in the literature; thus, they would benefit drug delivery and diagnostics for long term impact in cancer research.

Polysaccharide polymersome FRET probes for intracellular studies in live cells

ACS Spring Meeting 2021

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