Structural Engineering\nof Cationic Block Copolymer\nArchitectures for Selective Breaching of Prokaryotic and Eukaryotic\nBiological Species

Positively\ncharged antimicrobial polymers are known to cause severe\ndamage to biological systems, and thus synthetic strategies are urgently\nrequired to design next-generation nontoxic cationic macromolecular\narchitectures for healthcare applications. Here, we report a structural-engineering\nstrategy to build cationic linear and star-block copolymer nanoarchitectures\nhaving identical chemical composition, molar mass, nanoparticle size,\nand positive surface charge, yet they differ distinctly in their biological\naction in breaching prokaryotic species such as <i>E. coli</i> (Gram-negative bacteria) without affecting eukaryotic species like\nred-blood and mammalian cells. For this purpose, linear and star-block\nstructures are built on a polycaprolactone biodegradable platform\nhaving an imidazolium positive handle. Under physiological conditions,\nthe linear architecture exhibits toxicity indiscriminately to all\nbiological species, whereas its star counterpart is remarkably selective\nin membrane breaching action toward bacteria while maintaining inertness\ntoward eukaryotic species. Confocal microscopy analysis of HPTS fluorescent\ndye-loaded star-polymer nanoparticles substantiated their antimicrobial\naction in <i>E. coli</i>. Tissue-penetrable near-infrared\nfluorescent dye (IR-780) loaded NP aided the <i>in vivo</i> biodistribution analysis and <i>ex vivo</i> quantification\nof cationic species’ accumulations in vital organs in mice.\nAzithromycin, a clinical water-insoluble macrolide, is delivered from\nthe star platform to accomplish synergistic antimicrobial activity\nby the combination of bactericidal–bacteriostatic action of\nthe polymer carrier and drug together in a single system.