Wirelessly Powered Visible Light-Emitting Implant for Surgical Guidance during Lumpectomy.

Achieving negative surgical margins, defined as no tumor found on the edges of the resected tissue, during lumpectomy for breast cancer is critical for mitigating the risk of local recurrence. To identify nonpalpable tumors that cannot be felt, pre-operative placements of wire and wire-free localization devices are typically employed. Wire-free localization approaches have significant practical advantages over wired techniques. In this study, we introduce an innovative localization system comprising a light-emitting diode (LED)-based implantable device and handheld system. The device, which is needle injectable and wire free, utilizes multiple wirelessly powered LEDs to provide direct visual guidance for lumpectomy. Two distinct colors, red and blue, provide a clear indication of tissue depth: blue light is absorbed strongly in tissue, visible within a close range of <1 cm, while red light remains visible through several centimeters of tissue. The LEDs, integrated with an impedance-matching circuit and receiver coil, are encapsulated in biocompatible epoxy for injection with a 12 G needle. Our findings demonstrate that the implant exhibits clearly perceivable depth-dependent color changes and remains visible through >2 cm of ex vivo chicken breast and bovine muscle tissue using less than 4 W of transmitted power from a handheld antenna. These miniaturized needle-injectable localization devices show promise for improving surgical guidance of nonpalpable breast tumors.

Miniature wireless LED-device for photodynamic-induced cell pyroptosis.

The inability of visible light to penetrate far through biological tissue limits its use for phototherapy and photodiagnosis of deep-tissue sites of disease. This is unfortunate because many visible dyes are excellent photosensitizers and photocatalysts that can induce a wide range of photochemical processes, including photogeneration of reactive oxygen species. One potential solution is to bring the light source closer to the site of disease by using a miniature implantable LED. With this goal in mind, we fabricated a wireless LED-based device (volume of 23 mm3) that is powered by RF energy and emits light with a wavelength of 573 nm. It has the capacity to excite the green absorbing dye Rose Bengal, which is an efficient type II photosensitizer. The wireless transfer of RF power is effective even when the device is buried in chicken breast and located 6 cm from the transmitting antenna. The combination of a wireless device as light source and Rose Bengal as photosensitizer was found to induce cell death of cultured HT-29 human colorectal adenocarcinoma cells. Time-dependent generation of protruding bubbles was observed in the photoactivated cells suggesting cell death by light-induced pyroptosis and supporting evidence was gained by cell staining with the fluorescence probes Annexin-V FITC and Propidium Iodide. The results reveal a future path towards a wireless implanted LED-based device that can trigger photodynamic immunogenic cell death in deep-seated cancerous tissue.

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.

Measurements of acoustic radiation force of ultrahigh frequency ultrasonic transducers using model-based approach.

Even though ultrahigh frequency ultrasonic transducers over 60 MHz have been used for single-cell-level manipulation such as intracellular delivery, acoustic tweezers, and stimulation to investigate cell phenotype and cell mechanics, no techniques have been available to measure the actual acoustic radiation force (ARF) applied to target cells. Therefore, we have developed an approach to measure the ARF of ultrahigh frequency ultrasonic transducers using a theoretical model of the dynamics of a solid sphere in a gelatin phantom. To estimate ARF at the focus of a 130 MHz transducer, we matched measured maximum displacements of a solid sphere with theoretical calculations. We selected appropriate ranges of input voltages and pulse durations for single-cell applications, and the estimated ARF was in the range of tens of µN. To gauge the influence of pulse duration, an impulse of different pulse durations was estimated. Fluorescence resonance energy transfer live cell imaging was demonstrated to visualize calcium transport between cells after a target single cell was stimulated by the developed ultrasonic transducer.

Size-Dependent EPR Effect of Polymeric Nanoparticles on Tumor Targeting.

Passive targeting of large nanoparticles by the enhanced permeability and retention (EPR) effect is a crucial concept for solid tumor targeting in cancer nanomedicine. There is, however, a trade-off between the long-term blood circulation of nanoparticles and their nonspecific background tissue uptake. To define this size-dependent EPR effect, near-infrared fluorophore-conjugated polyethylene glycols (PEG-ZW800s; 1-60 kDa) are designed and their biodistribution, pharmacokinetics, and renal clearance are evaluated in tumor-bearing mice. The targeting efficiency of size-variant PEG-ZW800s is investigated in terms of tumor-to-background ratio (TBR). Interestingly, smaller sized PEGs (≤20 kDa, 12 nm) exhibit significant tumor targeting with minimum to no nonspecific uptakes, while larger sized PEGs (>20 kDa, 13 nm) accumulate highly in major organs, including the lungs, liver, and pancreas. Among those tested, 20 kDa PEG-ZW800 exhibits the highest TBR, while excreting unbound molecules to the urinary bladder. This result lays a foundation for engineering tumor-targeted nanoparticles and therapeutics based on the size-dependent EPR effect.