Understanding the control of the optical and plasmonic properties of unique nanosystems—gold nanostars—both experimentally and theoretically permits superior design and fabrication for biomedical applications. Here, we present a new, surfactant-free synthesis method of biocompatible gold nanostars with adjustable geometry such that the plasmon band can be tuned into the near-infrared region ‘tissue diagnostic window’, which is most suitable for in vivo imaging. Theoretical modelling was performed for multiple-branched 3D nanostars and yielded absorption spectra in good agreement with experimental results. The plasmon band shift was attributed to variations in branch aspect ratio, and the plasmon band intensifies with increasing branch number, branch length, and overall star size. Nanostars showed an extremely strong two-photon photoluminescence (TPL) process. The TPL imaging of wheat-germ agglutinin (WGA) functionalized nanostars on BT549 breast cancer cells and of PEGylated nanostars circulating in the vasculature, examined through a dorsal window chamber in vivo in laboratory mouse studies, demonstrated that gold nanostars can serve as an efficient contrast agent for biological imaging applications.

Gold nanoparticles have great potentials for plasmonic photothermal therapy (photothermolysis). However, their intracellular delivery and photothermolysis efficiency have yet been optimized. Here, we show that TAT-peptide functionalized gold nanostars enter cells significantly more than bare or PEGylated nanostars. Their major cellular uptake mechanism involves actin-driven lipid raft-mediated macropinocytosis, where particles primarily accumulate in macropinosomes but may also leak out into the cytoplasm. Following 4-hour incubation of TAT-nanostars on BT549 breast cancer cells, photothermolysis was accomplished using 850 nm pulsed laser under an irradiance of 0.2 W/cm2, which is lower than the maximal permissible exposure of skin. These results demonstrate the enhanced intracellular delivery and efficient photothermolysis of TAT-nanostars hence a promising agent in cancer therapy.

Nanomedicine has attracted increasing attention in recent years, because it offers great promise to provide personalized diagnostics and therapy with improved treatment efficacy and specificity. In this study, we developed a gold nanostar (GNS) probe for multi-modality theranostics including surface-enhanced Raman scattering (SERS) detection, x-ray computed tomography (CT), two-photon luminescence (TPL) imaging, and photothermal therapy (PTT). We performed radiolabeling, as well as CT and optical imaging, to investigate the GNS probe's biodistribution and intratumoral uptake at both macroscopic and microscopic scales. We also characterized the performance of the GNS nanoprobe for in vitro photothermal heating and in vivo photothermal ablation of primary sarcomas in mice. The results showed that 30-nm GNS have higher tumor uptake, as well as deeper penetration into tumor interstitial space compared to 60-nm GNS. In addition, we found that a higher injection dose of GNS can increase the percentage of tumor uptake. We also demonstrated the GNS probe's superior photothermal conversion efficiency with a highly concentrated heating effect due to a tip-enhanced plasmonic effect. In vivo photothermal therapy with a near-infrared (NIR) laser under the maximum permissible exposure (MPE) led to ablation of aggressive tumors containing GNS, but had no effect in the absence of GNS. This multifunctional GNS probe has the potential to be used for in vivo biosensing, preoperative CT imaging, intraoperative detection with optical methods (SERS and TPL), as well as image-guided photothermal therapy.

The vagus nerve (VN), the "great wondering protector" of the body, comprises an intricate neuro-endocrine-immune network that maintains homeostasis. With reciprocal neural connections to multiple brain regions, the VN serves as a control center that integrates interoceptive information and responds with appropriate adaptive modulatory feedbacks. While most VN fibers are unmyelinated C-fibers from the visceral organs, myelinated A- and B-fiber play an important role in somatic sensory, motor, and parasympathetic innervation. VN fibers are primarily cholinergic but other noncholinergic nonadrenergic neurotransmitters are also involved. VN has four vagal nuclei that provide critical controls to the cardiovascular, respiratory, and alimentary systems. Latest studies revealed that VN is also involved in inflammation, mood, and pain regulation, all of which can be potentially modulated by vagus nerve stimulation (VNS). With a broad vagal neural network, VNS may exert a neuromodulatory effect to activate certain innate "protective" pathways for restoring health.

The development of vagus nerve stimulation (VNS) began in the 19th century. Although it did not work well initially, it introduced the idea that led to many VNS-related animal studies for seizure control. In the 1990s, with the success of several early clinical trials, VNS was approved for the treatment of refractory epilepsy, and later for the refractory depression. To date, several novel electrical stimulating devices are being developed. New invasive devices are designed to automate the seizure control and for use in heart failure. Non-invasive transcutaneous devices, which stimulate auricular VN or carotid VN, are also undergoing clinical trials for treatment of epilepsy, pain, headache, and others. Noninvasive VNS (nVNS) exhibits greater safety profiles and seems similarly effective to their invasive counterpart. In this review, we discuss the history and development of VNS, as well as recent progress in invasive and nVNS.