Liposome-Tethered Gold Nanoparticles Triggered by Pulsed NIR Light for Rapid Liposome Contents Release and Endosome Escape.

Remote triggering of contents release with micron spatial and sub-second temporal resolution has been a long-time goal of medical and technical applications of liposomes. Liposomes can sequester a variety of bioactive water-soluble ions, ligands and enzymes, and oligonucleotides. The bilayer that separates the liposome interior from the exterior solution provides a physical barrier to contents release and degradation. Tethering plasmon-resonant, hollow gold nanoshells to the liposomes, or growing gold nanoparticles directly on the liposome exterior, allows liposome contents to be released by nanosecond or shorter pulses of near-infrared light (NIR). Gold nanoshells or nanoparticles strongly adsorb NIR light; cells, tissues, and physiological media are transparent to NIR, allowing penetration depths of millimeters to centimeters. Nano to picosecond pulses of NIR light rapidly heat the gold nanoshells, inducing the formation of vapor nanobubbles, similar to cavitation bubbles. The collapse of the nanobubbles generates mechanical forces that rupture bilayer membranes to rapidly release liposome contents at the preferred location and time. Here, we review the syntheses, characterization, and applications of liposomes coupled to plasmon-resonant gold nanostructures for delivering a variety of biologically important contents in vitro and in vivo with sub-micron spatial control and sub-second temporal control.

Mixed poly(vinyl pyrrolidone)-based drug-loaded nanomicelles shows enhanced efficacy against pancreatic cancer cell lines.

We report in this paper on the enhanced efficacy of a physical mixture of two single anti-cancer loaded nanomicelles against PANC-1 and BxPC-3. Poly(vinyl pyrrolidone-b-polycaprolactone) (PVP-b-PCL) and poly(vinyl pyrrolidone-b-poly(dioxanone-co-methyl dioxanone)) (PVP-b-P(DX-co-MeDX)) were synthesized and successfully loaded with various anti-cancer drugs - gemcitabine (GEM), doxorubicin.HCl (DOX.HCl), doxorubicin.NH2 (DOX), 5-fluorouracil (5-FU) and paclitaxel (PTX). Spherical micelles of size 160-477 nm were obtained as characterized by DLS while sizes determined by TEM were in the range 140-250 nm. The hydrophobic drugs had a higher loading percentage efficiency compared to hydrophilic drugs in the trend PTX>DOX>5-FU>GEM>DOX.HCl whereas the drug release pattern followed the reverse trend in accordance with decreased polymer-drug interaction as quantified by the binding constant and micellar drug location. Cellular uptake studies showed that nanomicelles are taken up by pancreatic cancer cells into the cytoplasm and nucleus. The free nanomicelles were confirmed to be non-cytotoxic. A physical mixture of GEM loaded micelles and DOX.HCl loaded micelles of comparable size showed significantly higher cytotoxicity than either the free drug mixture or the individual single drug loaded micelles as confirmed by their IC50 values.