A novel and modified fluorescent amphiphilic block copolymer simultaneously targeting to lysosomes and lipid droplets for cell imaging with large Stokes shift

Lipid droplets (LDs) and lysosomes are vital subcellular organelles which exist in almost all eukaryotic cells and play important roles in various physiological activities. In addition, recent studies showed that the interplay between LDs and lysosomes was related to metabolic diseases. Therefore, it is particularly meaningful for the medical field to develop an effective strategy to monitor lysosomes and LDs simultaneously aimed to understand the connection between them. However, single fluorescent tools for simultaneously visualizing LDs and lyso-somes were rarely reported and they may be faced to poor water solubility or high cytotoxicity. Herein, we designed and synthesized a novel 1,8-naphthalimide-based fluorescent monomer which can target to lysosomes and LDs simultaneously. The fluorescent monomer was applied to copolymerize with a hydrophilic material PEGMA(300) by reversible addition-fragmentation chain transfer polymerization (RAFT) for construction of fluorescent amphiphilic block copolymer Poly (Nap-Lyso-MMA-co-PEGMA(300)) for the first time, which exhibited good water solubility and photostability, large Stokes shift (almost 130 nm), good selectivity, low cytotoxicity, and wide pH stability. Furthermore, it was sensitive to the solvent polarity and lipo-solubility. We successfully achieved a series of bio-imaging applications such as cell imaging, lysosome-LDs dual-locating im-aging. These results indicated that the fluorescent copolymer possessed the remarkable bio-membrane pene-tration, lysosomes-targeting with the Pearson's Correlation of 0.832443, LDs-specificity with the Pearson's Correlation of 0.938595. Interestingly, fluorescent polymer could locate in dual-organelles simultaneously with different fluorescence signal, which could distinguish by the dot-fluorescence in LDs and the sheet-fluorescence in Lysosomes, accompanied by the brighter fluorescence in LDs than in Lysosomes. Based on these good prop-erties as mentioned above, we expect the synthetic fluorescent polyacrylate could serve as a promised candidate to understand the interplay between lysosomes and LDs for promoting progress in biomedical fields.