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The lipopolyplex, a multicomponent nonviral gene carrier, generally demonstrates superior colloidal stability, reduced cytotoxicity, and high transfection efficiency. In this study, a new concept, photochemical reaction-induced transfection, using photosensitizer (PS)-loaded lipopolyplexes was applied, which led to enhanced transfection and cytotoxic effects by photoexcitation of the photosensitizer. Hypericin, a hydrophobic photosensitizer, was encapsulated in the lipid bilayer of liposomes. The preformed nanosized hypericin liposomes enclosed the linear polyethylenimine (lPEI)/pDNA polyplexes, resulting in the formation of hypericin lipopolyplexes (Hy-LPP). The diameters of Hy-LPP containing 50 nM hypericin and 0.25 μg of pDNA were 185.6 ± 7.74 nm and 230.2 ± 4.60 nm, respectively, measured by dynamic light scattering (DLS) and atomic force microscopy (AFM). Gel electrophoresis confirmed the encapsulation of hypericin and pDNA in lipopolyplexes. Furthermore, in vitro irradiation of intracellular Hy-LPP at radiant exposures of 200, 600, and 1000 mJ/cm2was evaluated. It demonstrated 60- to 75-fold higher in vitro luciferase expression than that in nonirradiated cells. The lactate dehydrogenase (LDH) assay supported that reduced transfection was a consequence of photocytotoxicity. The developed photosensitizer-loaded lipopolyplexes improved the transfection efficiency of an exogenous gene or induced photocytotoxicity; however, the frontier lies in the applied photochemical dose. The light-triggered photoexcitation of intracellular hypericin resulted in the generation of reactive oxygen species (ROS), leading to photoselective transfection in HepG2 cells. It was concluded that the two codelivered therapeutics resulted in enhanced transfection and a photodynamic effect by tuning the applied photochemical dose.

Antimicrobial strategies with high efficacy against bacterial infections are urgently needed. The development of effective therapies to control bacterial infections is still a challenge. Herein, near-infrared (NIR)-activated thermosensitive liposomes (TSL) were loaded with the NIR-dye 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR) and the water-soluble hypericin (Hyp) β-cyclodextrin inclusion complex (Hyp-βCD). DiR and Hyp-βCD loaded thermosensitive liposomes (DHβCD-TSL) are functionalized for photothermal triggered release and synergistic photodynamic therapy to eliminate the gram-positive Staphylococcus saprophyticus. The dually active liposomes allow the production of heat and singlet oxygen species with the help of DiR and Hyp, respectively. The elevated temperature, generated by the NIR irradiation, irreversibly damages the bacterial membrane, increases the permeation, and melts the liposomes via a phase-transition mechanism, which allows the release of the Hyp-βCD complex. The photodynamic effect of Hyp-βCD eradicates the bacterial cells owing to its toxic oxygen species production. DHβCD-TSL measured the size of 130 nm with an adequate encapsulation efficiency of 81.3% of Hyp-βCD. They exhibited a phase transition temperature of 42.3 °C, while they remained stable at 37 °C, and 44% of Hyp-βCD was released after NIR irradiation (T> 47 °C). The bacterial viability dropped significantly after the synergistic treatment (>4 log10), indicating that the NIR-activated TSL have immense therapeutic potential to enhance the antibacterial efficacy. The liposomes showed good biocompatibility, which was confirmed by the cellular viability of mouse fibroblasts (L929).

Photodynamic therapy (PDT) is a minimally invasive tumor targeting strategy, in which tumor tissues can be selectively destroyed. Upon excitation with light of a specific wavelength, a photosensitizer can produce reactive oxygen species (ROS) in the presence of molecular oxygen, thereby exhibiting a cytotoxic effect toward the surrounding tissues, giving a total control on the onset of therapy. In this research work, curcumin as a natural photosensitizer has been investigated against cancer cells. To enhance the solubility of curcumin, a nanoformulation is developed using chitosan as biodegradable and biocompatible polymer that has the ability to encapsulate curcumin and improve its therapeutic effect. Physicochemical characterizations revealed that the prepared formulations were in the nanoscale range and had a positive ζ‐potential. Upon irradiation using a novel LED device (λex= 457 nm), curcumin nanoparticles were able to generate ROS and destroy tumor cells. Moreover, unloaded nanoparticles exhibited nonsignificant phototoxicity. These outcomes confirm the importance of curcumin nanoparticles in enhancing the efficacy of curcumin and offer new insights in the field of PDT against cancer. Scheme of chitosan nanoparticles preparation and their effectivenessagainst tumor cells upon irradiation.