Abstract
The delivery of therapeutic compounds to target tissues is a central challenge in treating disease. Externally controlled drug release systems hold potential to selectively enhance localized delivery. Here we describe liposomes doped with porphyrin–phospholipid that are permeabilized directly by near-infrared light. Molecular dynamics simulations identified a novel light-absorbing monomer esterified from clinically approved components predicted and experimentally demonstrated to give rise to a more stable porphyrin bilayer. Light-induced membrane permeabilization is enabled with liposomal inclusion of 10 molar % porphyrin–phospholipid and occurs in the absence of bulk or nanoscale heating. Liposomes reseal following laser exposure and permeability is modulated by varying porphyrin–phospholipid doping, irradiation intensity or irradiation duration. Porphyrin–phospholipid liposomes demonstrate spatial control of release of entrapped gentamicin and temporal control of release of entrapped fluorophores following intratumoral injection. Following systemic administration, laser irradiation enhances deposition of actively loaded doxorubicin in mouse xenografts, enabling an effective single-treatment antitumour therapy.
Highlights
The delivery of therapeutic compounds to target tissues is a central challenge in treating disease
Molecular dynamics (MD) simulations are used to identify a stable new porphyrin–lipid monomer that gives rise to more stable bilayers
We recently discovered that PoP can selfassemble into liposome-like porphysome nanovesicles formed entirely from a porphyrin bilayer with intrinsic biophotonic character, nanoscale optical properties, biocompatibility and biodegradability[27,28,29]
Summary
The delivery of therapeutic compounds to target tissues is a central challenge in treating disease. Delivery is hampered by physiological barriers and release kinetics so that biodistribution and bioavailability are almost inevitably suboptimal[3,4] To address this problem, numerous diverse strategies have been pursued that make use of external stimuli to trigger local drug release[5,6,7,8,9]. Liposomal release based on heating to lipid phase-transition temperatures has been expanded to other thermal transduction methods including ultrasonic tissue heating[14], magnetic field heating using magnetoliposomes[15,16] and near-infrared (NIR) photothermal heating via gold coating[17,18], tethering[19] and co-administration[20]. Using temperature-triggered nanocarriers with phase transitions at even higher temperatures is not practical, as the elevated heating required for release would in itself destroy the target tissue and could induce stasis within tumour vesicles that could impede drug delivery[25]. PoP-liposomes can be loaded with a range of cargos including fluorophores, antibiotics and chemotherapeutics, and release these on demand with excellent spatial and temporal control
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