Injectable Thermosensitive Hydrogels for a Sustained Release of Iron Nanochelators.

Deferoxamine (DFO) is an FDA-approved iron-chelating agent which shows good therapeutic efficacy, however, its short blood half-life presents challenges such as the need for repeated injections or continuous infusions. Considering the lifelong need of chelating agents for iron overload patients, a sustained-release formulation that can reduce the number of chelator administrations is essential. Here, injectable hydrogel formulations prepared by integrating crosslinked hyaluronic acid into Pluronic F127 for an extended release of DFO nanochelators are reported. The subcutaneously injected hydrogel shows a thermosensitive sol-gel transition at physiological body temperature and provides a prolonged release of renal clearable nanochelators over 2 weeks, resulting in a half-life 47-fold longer than that of the nanochelator alone. In addition, no chronic toxicity of the nanochelator-loaded hydrogel is confirmed by biochemical and histological analyses. This injectable hydrogel formulation with DFO nanochelators has the potential to be a promising formulation for the treatment of iron overload disorders.

A dual modal silver bumpy nanoprobe for photoacoustic imaging and SERS multiplexed identification of in vivo lymph nodes.

Multimodal imaging can provide complementary biomedical information which has huge potential in pre-clinical and clinical imaging and sensing. In this study, we introduce dual modal NIR silver bumpy nanoprobes for in vivo imaging and multiplexed detection of biomolecules by both photoacoustic imaging (PAI) and surface-enhanced Raman scattering (SERS) techniques. For this study, we used silica-coated silver bumpy nanoshell probes (AgNS@SiO2). AgNS@SiO2 have strong NIR-absorption and scattering properties compared with other nanostructures, and therefore, can be a good candidate for photoacoustic (PA) and SERS multimodal imaging. We obtained PA images of the skin and SLNs of rats by injecting various kinds of Raman-labeled AgNS@SiO2. Multiplexed identification of the injected AgNS@SiO2 was achieved by measuring SERS signals. AgNS@SiO2 have the potential to be applied in detecting cancer biomarkers by locating biomarkers quickly using PA imaging, and identification by multiplexed target measurement using SERS signals in vivo.

Target-specific near-IR induced drug release and photothermal therapy with accumulated Au/Ag hollow nanoshells on pulmonary cancer cell membranes.

Au/Ag hollow nanoshells (AuHNSs) were developed as multifunctional therapeutic agents for effective, targeted, photothermally induced drug delivery under near-infrared (NIR) light. AuHNSs were synthesized by galvanic replacement reaction. We further conjugated antibodies against the epidermal growth factor receptor (EGFR) to the PEGylated AuHNS, followed by loading with the antitumor drug doxorubicin (AuHNS-EGFR-DOX) for lung cancer treatment. AuHNSs showed similar photothermal efficiency to gold nanorods under optimized NIR laser power. The targeting of AuHNS-EGFR-DOX was confirmed by light-scattering images of A549 cells, and doxorubicin release from the AuHNSs was evaluated under low pH and NIR-irradiated conditions. Multifunctional AuHNS-EGFR-DOX induced photothermal ablation of the targeted lung cancer cells and rapid doxorubicin release following irradiation with NIR laser. Furthermore, we evaluated the effectiveness of AuHNS-EGFR-DOX drug delivery by comparing two drug delivery methods: receptor-mediated endocytosis and cell-surface targeting. Accumulation of the AuHNS-EGFR-DOX on the cell surfaces by targeting EGFR turned out to be more effective for lung cancer treatments than uptake of AuHNS-EGFR-DOX. Taken together, our data suggest a new and optimal method of NIR-induced drug release via the accumulation of targeted AuHNS-EGFR-DOX on cancer cell membranes.