One-Pot, One-Step Synthesis of Drug-Loaded Magnetic Multimicelle Aggregates.

Lipid-based formulations provide a nanotechnology platform that is widely used in a variety of biomedical applications because it has several advantageous properties including biocompatibility, reduced toxicity, relative ease of surface modifications, and the possibility for efficient loading of drugs, biologics, and nanoparticles. A combination of lipid-based formulations with magnetic nanoparticles such as iron oxide was shown to be highly advantageous in a growing number of applications including magnet-mediated drug delivery and image-guided therapy. Currently, lipid-based formulations are prepared by multistep protocols. Simplification of the current multistep procedures can lead to a number of important technological advantages including significantly decreased processing time, higher reaction yield, better product reproducibility, and improved quality. Here, we introduce a one-pot, single-step synthesis of drug-loaded magnetic multimicelle aggregates (MaMAs), which is based on controlled flow infusion of an iron oxide nanoparticle/lipid mixture into an aqueous drug solution under ultrasonication. Furthermore, we prepared molecular-targeted MaMAs by directional antibody conjugation through an Fc moiety using Cu-free click chemistry. Fluorescence imaging and quantification confirmed that antibody-conjugated MaMAs showed high cell-specific targeting that was enhanced by magnetic delivery.

Endobronchial ultrasound-guided injection of NBTXR3 radio-enhancing nanoparticles into mediastinal and hilar lymph nodes: a swine model to evaluate feasibility, injection technique, safety, nanoparticle retention and dispersion.

BACKGROUND: Loco-regionally advanced lung cancer is typically treated with a combination of chemotherapy and radiation therapy, but overall survival and local control remain poor. Radio-enhancing nanoparticles such as NBTXR3 activated by radiotherapy results in increased cell death and potentially an anti-tumor immune response. The goal of this study was to assess the feasibility and safety of endobronchial ultrasound (EBUS)-guided injection of NBTXR3 into mediastinal and hilar lymph nodes (LN), as well as assess nanoparticle retention in the LN post-injection. METHODS: Animals underwent bronchoscopy under general anesthesia with EBUS-guided injection of NBTXR3 into hilar and mediastinal LN. LN and injection volumes were calculated based on pre-injection computed tomography (CT) scans. CT scans were repeated at 5 min, 30 min, and 8 days post-injection. Blood-draws were also obtained at baseline and post-injection. Animals were then housed, monitored, and sacrificed 8 days post-injection. Necropsy was then performed with gross and histologic analysis of LN. RESULTS: A total of 20 LN were injected in 5 pigs (4 LN per animal). Nanoparticles were retained in 100% of LN at 30 min, and 90% of LN at 8 days. Extravasation of nanoparticles was seen in 4 out of the 20 LN. There were no cases of nanoparticle embolization visible by CT in distant organs. Small air-bubbles were introduced in the targets and surrounding tissue in 3 out of 20 LN. Of note, at 8 days, none of these air-bubbles were present on CT scan. There were no intra-procedural or post-procedural complications in either CT scans or necropsy findings. Pigs remained clinically stable and neither laboratory values nor necropsy showed evidence of inflammation. CONCLUSIONS: EBUS-guided injection of NBTXR3 radio-enhancing nanoparticles can be safely performed achieving a high rate of nanoparticle retention, low extravasation, and no visible nanoparticle embolization.

Multifunctional Cu2-xTe Nanocubes Mediated Combination Therapy for Multi-Drug Resistant MDA MB 453.

Hypermethylated cancer populations are hard to treat due to their enhanced chemo-resistance, characterized by aberrant methylated DNA subunits. Herein, we report on invoking response from such a cancer lineage to chemotherapy utilizing multifunctional copper telluride (Cu2-XTe) nanocubes (NCs) as photothermal and photodynamic agents, leading to significant anticancer activity. The NCs additionally possessed photoacoustic and X-ray contrast imaging abilities that could serve in image-guided therapeutic studies.

Multi-stimuli responsive Cu2S nanocrystals as trimodal imaging and synergistic chemo-photothermal therapy agents.

A size and shape tuned, multifunctional metal chalcogenide, Cu2S-based nanotheranostic agent is developed for trimodal imaging and multimodal therapeutics against brain cancer cells. This theranostic agent was highly efficient in optical, photoacoustic and X-ray contrast imaging systems. The folate targeted NIR-responsive photothermal ablation in synergism with the chemotherapeutic action of doxorubicin proved to be a rapid precision guided cancer-killing module. The multi-stimuli, i.e., pH-, thermo- and photo-responsive drug release behavior of the nanoconjugates opens up a wider corridor for on-demand triggered drug administration. The simple synthesis protocol, combined with the multitudes of interesting features packed into a single nanoformulation, clearly demonstrates the competing role of this Cu2S nanosystem in future cancer treatment strategies.