Multifunctional nanomaterials have the potential to integrate the clinical paradigms of imaging and therapy to enable real-time visualization of therapeutic biodistributions in patients. For cancer therapy, nanomaterials with capacities to be remotely detected and triggered for therapy could also close the loop between tumor detection and treatment. In this work, we show that the near-infrared plasmon resonance of gold nanorods (NRs) may be exploited to provide an integrated platform for multiplexed Raman detection and remote-controlled photothermal heating. By screening mixed-monolayer NRs, coated with polyethyleneglycol polymers alongside visible-and NIR-absorbing molecules, we achieved surface-enhanced, resonant Raman scattering (SERRS) and identified three NR formulations that may be uniquely distinguished over a spectral bandwidth of only 6 nm in the near-infrared, a spectral multiplexing density over an order of magnitude greater than attainable with semiconductor quantum dots, [1] organic fluorochromes, and Raleigh scattering nanoparticle imaging approaches. [2][3][4][5] Given the characteristic Raman fingerprint of the molecular labels on the NRs, we refer to them hereafter as SERS-coded NRs. SERS-coded NRs are found to be highly stable, to be detectable down to attomolar particle concentrations, and to have low baseline cytoxicity in vitro. In vivo, SERS-coded NRs were efficiently detected following subcutaneous or intratumoral injection and enabled remote photothermal tumor heating to ablative temperatures. In the future, the dense near-infrared spectral multiplexing of gold NRs should catalyze efficient, multivariable screening of NR surface chemistries in a single animal host, as well as provide a route towards characterizing multicomponent nanoparticle systems with cooperative in vivo functions.Raman imaging of nanomaterials has recently emerged as an attractive alternative to fluorescence approaches. [6][7][8][9][10] Raman spectroscopy is a desirable modality for in vivo imaging because, as opposed to semiconductor quantum dot labels,[1] Raman scattering may be both efficiently excited and detected within the near-infrared optical window ($700-900 nm), where endogenous tissue absorption coefficients are over two orders of magnitude lower than for blue and ultra-violet light.[11] Raman detection is also considerably less sensitive to photobleaching than fluorescence [7,12] and the characteristic bandwidths of Raman lines are up to two orders of magnitude narrower than for fluorescence. To date, Raman scattering from nanomaterials has been utilized to improve diagnostic sensitivity in vitro, [10,[13][14][15] to probe subcellular environments, [16,17] and, very recently, to track spherical gold nanoparticles [6,7] and carbon nanotubes [18] in vivo. These in vivo studies highlight the potential for Raman spectroscopy to serve as an ultra-sensitive medical imaging modality.In addition to their applications in diagnosis and imaging, plasmonic materials have recently attracted attention for their potential...

The targeted delivery of therapeutics to tumors remains an important challenge in cancer nanomedicine. Attaching nanoparticles to cells that have tumoritropic migratory properties is a promising modality to address this challenge. Here we describe a technique to create nanoparticulate cellular patches that remain attached to the membrane of cells for up to 2 days. Neutravidin-coated nanoparticles were anchored on cells by binding to biotinylated plasma membrane. Human bone marrow derived mesenchymal stem cells with nanoparticulate patches retained their inherent tumoritropic properties as shown using a tumor model in a 3D extracellular matrix (P-value < 0.001). Additionally, Human umbilical vein endothelial cells with nanoparticulate patches were able to retain their functional properties and form multicellular structures as rapidly as unmodified endothelial cells. These results provide a novel strategy to actively deliver nanostructures and therapeutics to tumors utilizing stem cells as carriers, and also suggest that nanoparticulate cellular patches may have applications in tissue regeneration.

Current approaches for topical vaginal administration of nanoparticles result in poor retention and extensive leakage. To overcome these challenges, we developed a nanoparticle-releasing nanofiber delivery platform and evaluated its ability to improve nanoparticle retention in a murine model. We individually tailored two components of this drug delivery system for optimal interaction with mucus, designing (1) mucoadhesive fibers for better retention in the vaginal tract, and (2) PEGylated nanoparticles that diffuse quickly through mucus. We hypothesized that this novel dual-functioning (mucoadhesive/mucus–penetrating) composite material would provide enhanced retention of nanoparticles in the vaginal mucosa. Equivalent doses of fluorescent nanoparticles were vaginally administered to mice in either water (aqueous suspension) or fiber composites, and fluorescent content was quantified in cervicovaginal mucus and vaginal tissue at time points from 24h to 7d. We also fabricated composite fibers containing etravirine-loaded nanoparticles and evaluated the pharmacokinetics over 7d. We found that our composite materials provided approximately 30-fold greater retention of nanoparticles in the reproductive tract at 24h compared to aqueous suspensions. Compared to nanoparticles in aqueous suspension, the nanoparticles in fiber composites exhibited sustained and higher etravirine concentrations after 24h and up to 7d, demonstrating the capabilities of this new delivery platform to sustain nanoparticle release out to 3d and drug retention out to one week after a single administration. This is the first report of nanoparticle-releasing fibers for vaginal drug delivery, as well as the first study of a single delivery system that combines two components uniquely engineered for complementary interactions with mucus.

Nanocarriers are versatile vehicles for drug delivery, and emerging as platforms to formulate and deliver multiple classes of antiretroviral (ARV) drugs in a single system. Here we describe the fabrication of hydrogel-core and lipid-shell nanoparticles (nanolipogels) for the controlled loading and topical, vaginal delivery of maraviroc (MVC) and tenofovir disoproxil fumarate (TDF), two ARV drugs with different mechanisms of action that are used in the treatment of HIV. The nanolipogel platform was used to successfully formulate MVC and TDF, which produced ARV drug-loaded nanolipogels that were characterized for their physical properties and antiviral activity against HIV-1 BaL in cell culture. We also show that administration of these drug carriers topically to the vaginal mucosa in a murine model leads to antiviral activity against HIV-1 BaL in cervicovaginal lavages. Our results suggest that nanolipogel carriers are promising for the encapsulation and delivery of hydrophilic small molecule ARV drugs, and may expand the nanocarrier systems being investigated for HIV prevention or treatment.