Delayed photolysis of liposomes: a strategy for the precision timing of bolus drug release using ex-vivo photochemical sensitization
2012
Chemotherapy is a standard treatment for metastatic cancer. However drug toxicity limits the dosage that can safely
be used, thus reducing treatment efficacy. Drug carrier particles, like liposomes, can help reduce toxicity by
shielding normal tissue from drug and selectively depositing drug in tumors. Over years of development, liposomes
have been optimized to avoid uptake by the Reticuloendothelial System (RES) as well as effectively retain their drug
content during circulation. As a result, liposomes release drug passively, by slow leakage, but this uncontrolled drug
release can limit treatment efficacy as it can be difficult to achieve therapeutic concentrations of drug at tumor sites
even with tumor-specific accumulation of the carriers. Lipid membranes can be photochemically lysed by both
Type I (photosensitizer-substrate) and Type II (photosensitizer-oxygen) reactions. It has been demonstrated in red
blood cells (RBCs) in vitro that these photolysis reactions can occur in two distinct steps: a light-initiated reaction
followed by a thermally-initiated reaction. These separable activation steps allow for the delay of photohemolysis in
a controlled manner using the irradiation energy, temperature and photosensitizer concentration. In this work we
have translated this technique from RBCs to liposomal nanoparticles. To that end, we present in vitro data
demonstrating this delayed bolus release from liposomes, as well as the ability to control the timing of this event.
Further, we demonstrate for the first time the improved delivery of bioavailable cargo selectively to target sites in
vivo.
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