The ability of glucagon-like peptide-1 analogs to enhance glucose-dependent insulin secretion and to inhibit β cell apoptosis could be of potential benefit for islet transplantation. In this study, we investigated the effect of sustained local delivery of exenatide, a synthetic exendin-4, on the in vitro viability and function of encapsulated porcine islets. Prior to encapsulation, we fabricated exenatide-loaded poly(latic-co-glycolic acid) microspheres, and investigated their release behavior with different initial drug-loading amounts. Exenatide-loaded microspheres, exhibiting a sustained release over 21 days, were subsequently chosen and co-encapsulated with porcine islets in alginate microcapsules. During the 21-day period, the islets co-encapsulated with the exenatide-loaded microspheres exhibited improved survival and glucose-stimulated insulin secretion, compared to those without. This suggested that the intracapsular sustained delivery of exenatide via microspheres could be a promising strategy for improving survival and function of microencapsulated porcine islets for islet xenotransplantation.
Real-time guidance through fluorescence imaging improves
the surgical
outcomes of tumor resections, reducing the chances of leaving positive
margins behind. As tumors are heterogeneous, it is imperative to interrogate
multiple overexpressed cancer biomarkers with high sensitivity and
specificity to improve surgical outcomes. However, for accurate tumor
delineation and ratiometric detection of tumor biomarkers, current
methods require multiple excitation wavelengths to image multiple
biomarkers, which is impractical in a clinical setting. Here, we have
developed a biomimetic platform comprising near-infrared fluorescent
semiconducting polymer nanoparticles (SPNs) with red blood cell membrane
(RBC) coating, capable of targeting two representative cell-surface
biomarkers (folate, αυβ3 integrins) using a single
excitation wavelength for tumor delineation during surgical interventions.
We evaluate our single excitation ratiometric nanoparticles in in vitro tumor cells, ex vivo tumor-mimicking
phantoms, and in vivo mouse xenograft tumor models.
Favorable biological properties (improved biocompatibility, prolonged
blood circulation, reduced liver uptake) are complemented by superior
spectral features: (i) specific fluorescence enhancement in tumor
regions with high tumor-to-normal tissue (T/NT) ratios in ex vivo samples and (ii) estimation of cell-surface tumor
biomarkers with single wavelength excitation providing insights about
cancer progression (metastases). Our single excitation, dual output
approach has the potential to differentiate between the tumor and
healthy regions and simultaneously provide a qualitative indicator
of cancer progression, thereby guiding surgeons in the operating room
with the resection process.
Tumor-targeted fluorescent probes in the near-infrared spectrum can provide invaluable information about the location and extent of primary and metastatic tumors during intraoperative procedures to ensure no residual tumors are...
.
Significance
Near-infrared fluorescence image-guided surgery is often thought of as a spectral imaging problem where the channel count is the critical parameter, but it should also be thought of as a multiscale imaging problem where the field of view and spatial resolution are similarly important.
Aim
Conventional imaging systems based on division-of-focal-plane architectures suffer from a strict relationship between the channel count on one hand and the field of view and spatial resolution on the other, but bioinspired imaging systems that combine stacked photodiode image sensors and long-pass/short-pass filter arrays offer a weaker tradeoff.
Approach
In this paper, we explore how the relevant changes to the image sensor and associated image processing routines affect image fidelity during image-guided surgeries for tumor removal in an animal model of breast cancer and nodal mapping in women with breast cancer.
Results
We demonstrate that a transition from a conventional imaging system to a bioinspired one, along with optimization of the image processing routines, yields improvements in multiple measures of spectral and textural rendition relevant to surgical decision-making.
Conclusions
These results call for a critical examination of the devices and algorithms that underpin image-guided surgery to ensure that surgeons receive high-quality guidance and patients receive high-quality outcomes as these technologies enter clinical practice.
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