Dynamic control of neurochemical release with ultrasonically-sensitive nanoshell-tethered liposomes

The unique surface plasmon resonance of hollow gold nanoshells can be used to achieve drug release from liposomes upon laser stimulation, and adapted to mimic the intricate dynamics of neurotransmission ex vivo in brain preparations. However, to induce a physiological response in vivo requires the degree of temporal precision afforded by laser stimulation, but with a greater depth of penetration through tissue. Here we report that the attachment of hollow gold nanoshells to the surface of robust liposomes results in a construct that is highly sensitive to ultrasonic stimulation. The resulting construct can be remotely triggered by low intensity, therapeutic ultrasound. To our knowledge, this is the first example of nanoparticle-liposome system that can be activated by both laser and acoustic stimulation. The system is capable of encapsulating the neurochemical dopamine, and repeatedly releasing small amounts on-demand in a circulating environment, allowing for precise spatiotemporal control over the release profile.

Hollow gold nanoshells-incorporated injectable genetically engineered hydrogel for sustained chemo-photothermal therapy of tumor

Background Combined therapy has demonstrated to be an effective strategy for cancer therapy. Herein, an injectable hydrogel based on the genetically engineered polypeptide and hollow gold nanoshells (HAuNS) has been developed for chemo-photothermal therapy of HepG2 tumor. Methods PC10A/DOX/HAuNS nanogel was prepared with layer-by-layer through the adsorption of DOX and PC10A successively. DOX with positive charge and PC10A with negative charge were coated step by step onto the surface of negatively charged HAuNS. The multifunctional hydrogel PC10A/DOX/HAuNS were prepared via dissolving hybrid PC10A/DOX/HAuNS nanogel in polypeptide PC10A. Chemotherapy drug DOX in the PC10A/DOX/HAuNS hydrogel was absorbed on the HAuNS and directly embedded in the PC10A hydrogel, which contributes to sequentially release of the drug. Specifically, DOX adsorbed on the HAuNS could be released slowly for sustainable chemotherapy. Results The PC10A/DOX/HAuNS hydrogel could pass 26-gauge needle without clogging, indicating that it is injectable. In addition, the PC10A/DOX/HAuNS hydrogel possessed outstanding photothermal effect and photothermal stability. In both in vitro cell and in vivo tumor-bearing mice experiments, a remarkably enhance tumor inhibition was observed by the combined therapy of chemo-photothermal therapy compared with photothermal therapy or chemotherapy alone. Conclusions The combined chemotherapy and photothermal therapy of PC10A/DOX/HAuNS hydrogels could significantly improve the therapeutic effect. Therefore, the multifunctional hydrogel PC10A/DOX/HAuNS is promising to provide a new strategy for sustained chemo-photothermal therapy.