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Liposomes show great promise as intravenous drug delivery vehicles, but it is difficult to combine stability in the
circulation, extended drug retention and rapid, targeted release at the site of interest. Accessorizing conventional and
multicompartment liposomes with photo-activated hollow gold nanoshells (HGN) provides a convenient method to
initiate drug release with spatial and temporal control. HGN efficiently absorb near infrared (NIR) light and rapidly
convert the absorbed optical energy into heat. Femto- to nano-second NIR light pulses cause the HGNs to rapidly heat,
creating large temperature gradients between the HGNs and surrounding fluid. The formation and collapse of unstable
vapor bubbles transiently rupture liposome and other bilayer membranes to trigger contents release. Near-complete
contents release occurs when the nanoshells are encapsulated within the liposome or tethered to the outer surface of the
liposome, with no chemical damage to the contents. Release is achieved by focusing the laser beam at the target,
eliminating the need for highly specific targeting ligands or antibodies. Although HGN heating can be intense, the
overall energy input is small causing minimal heating of the surroundings. To ensure that drugs are retained within the
liposomes until delivery in a physiological environment, we have made novel multicompartment carriers called
vesosomes, which consist of an outer lipid bilayer shell that encloses and protects the drug-carrying liposomes. The
second bilayer increases the serum half-life of ciprofloxacin from <10 minutes in liposomes to 6 hours in vesosomes
and alters the release kinetics. The enhanced drug retention is due to the outer membrane preventing enzymes and
proteins in the blood from breaking down the drug-carrying interior compartments.
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