Tailoring Phage Nanosomes for Enhanced Theranostic Properties of Near Infrared Dyes

Near-infrared (NIR) phototherapies offer noninvasive, cost-effective solutions for treating tumors and microbial infections. However, organic NIR dyes commonly used suffer from solubility and stability issues requiring frequent dosing. We address this challenge by exploring the bacteriophage-mediated enhancement of NIR dye properties. Upon encapsulation within phage nanosomes, IR780 and Indocyanine green (ICG), with similar optical properties but distinct water solubility and exhibit enhanced UV-vis absorbance and photothermal transduction efficacy compared to liposomes. Experimental characterization corroborated with all-atom molecular dynamics simulations imprints the nanoscale structure, solubility, dynamics, and binding of these NIR dye molecules to the membrane and protein molecules present in Phage capsid. These NIR dye-loaded phage nanosomes, coencapsulated with mitoxantrone, demonstrate enhanced anticancer activity, and when combined with amphotericin B, these dye molecules exhibit superior photothermal effects against fungal infections. Our findings present a simple and efficient approach for tuning the photothermal performance of existing NIR dyes through a rational design for enhanced therapeutic outcomes.