Vaccines based on recombinant proteins avoid toxicity and anti-vector immunity associated with live vaccine (e.g., viral) vectors, but their immunogenicity is poor, particularly for CD8+ T-cell (CD8T) responses. Synthetic particles carrying antigens and adjuvant molecules have been developed to enhance subunit vaccines, but in general these materials have failed to elicit CD8T responses comparable to live vectors in preclinical animal models. Here, we describe interbilayer-crosslinked multilamellar vesicles (ICMVs) formed by crosslinking headgroups of adjacent lipid bilayers within multilamellar vesicles. ICMVs stably entrapped protein antigens in the vesicle core and lipid-based immunostimulatory molecules in the vesicle walls under extracellular conditions, but exhibited rapid release in the presence of endolysosomal lipases. We found that these antigen/adjuvant-carrying ICMVs form an extremely potent whole-protein vaccine, eliciting endogenous T-cell and antibody responses comparable to the strongest vaccine vectors. These materials should enable a range of subunit vaccines and provide new possibilities for protein therapeutic delivery.

An elusive goal for systemic drug delivery is to provide both spatial and temporal control of drug release. Liposomes have been evaluated as drug delivery vehicles for decades 1-5 , but their clinical significance has been limited by slow release or poor availability of the encapsulated drug 6 . Here we show that near-complete liposomal release can be initiated within seconds by irradiating hollow gold nanoshells (HGNs) with a near-infrared (NIR) pulsed laser. Our findings reveal that different coupling methods, such as having the HGNs tethered to, encapsulated within, or suspended freely outside the liposomes, all triggered liposomal release but with different levels of efficiency. For the underlying content release mechanism, our experiments suggest that microbubble formation and collapse due to the rapid temperature increase of the HGN is responsible for liposome disruption, as evidenced by the formation of solid gold particles after NIR irradiation and the coincidence of a laser power threshold for both triggered release and pressure fluctuations in the solution associating with cavitations. These effects are similar to those induced by ultrasound and our approach is conceptually analogous to use optically triggered nano-"sonicators" deep inside the body for drug delivery. We expect HGNs can be coupled with any nanocarriers to promote spatially and temporally controlled drug release. In addition, the capability of external HGNs to permeabilize lipid membranes can facilitate the cellular uptake of macromolecules, including proteins and DNA and allow for promising applications in gene therapy.One major challenge for current drug delivery is to control the drug release both spatially and temporally. Liposomes have been evaluated as drug delivery vehicles for decades 1-5 , but their clinical significance has been limited by slow release or poor availability of the encapsulated drug 6 . Here we show that near-complete liposomal release can be initiated within seconds ("burst" kinetics) by irradiating hollow gold nanoshells (HGNs) with a near-infrared (NIR) pulsed laser. Tissues are relatively transparent to NIR light which penetrates into body up to 10 cm 7 . This allows these HGN/liposome complexes to be addressed non-invasively within a significant fraction of the human body. Our findings on the underlying release mechanism reveal that this approach is conceptually analogous to using optically triggered nano-"sonicators" deep inside the body for drug delivery. Email: gorilla@engineering.ucsb Liposomes optimized to be highly stable and resistant to drug leakage in the circulation 8,9 are hampered by suboptimal drug release to serve as drug carriers. Current endogenous strategies in drug release have focused on incorporating components into liposomes to achieve either thermal, pH, enzymatically triggered or receptor-targeted liposomes 3-5 , however, none of them has led to marketed drugs 10 . It is difficult to include a destabilizing agent into the liposomes to promote release without compromising their ...

Synaptotagmin acts as a Ca(2+) sensor in neurotransmitter release through its two C(2) domains. Ca(2+)-dependent phospholipid binding is key for synaptotagmin function, but it is unclear how this activity cooperates with the SNARE complex involved in release or why Ca(2+) binding to the C(2)B domain is more crucial for release than Ca(2+) binding to the C(2)A domain. Here we show that Ca(2+) induces high-affinity simultaneous binding of synaptotagmin to two membranes, bringing them into close proximity. The synaptotagmin C(2)B domain is sufficient for this ability, which arises from the abundance of basic residues around its surface. We propose a model wherein synaptotagmin cooperates with the SNAREs in bringing the synaptic vesicle and plasma membranes together and accelerates membrane fusion through the highly positive electrostatic potential of its C(2)B domain.

We report the nanoscale loading and confinement of aquated Gd3+n-ion clusters within ultra-short single-walled carbon nanotubes (US-tubes); these Gd3+n@US-tube species are linear superparamagnetic molecular magnets with Magnetic Resonance Imaging (MRI) efficacies 40 to 90 times larger than any Gd3+-based contrast agent (CA) in current clinical use.