A new group of “clickable” and brightly emissive metalloporphyrins has been developed for the visualization of oxygenation under ambient light by eye. These alkynyl-terminated compounds permit the rapid and facile synthesis of oxygen-sensing dendrimers through azide-alkyne click chemistry. With absorption maxima overlapping with the wavelengths of common commercial laser sources, they are readily applicable to biomedical imaging of tissue oxygenation. An efficient synthetic methodology, featuring the stable trimethylacetyl (pivaloyl) protecting group, is described for their preparation. A paint-on liquid bandage containing a new, click-synthesized porphyrin dendrimer has been used to map oxygenation across an ex vivo porcine skin burn model. A group of easy-to-use, mass-producible sensors should spur major advances in both clinical use and basic research in the field of oxygen sensing.

Photodynamic therapy regimens, which use light-activated molecules known as photosensitizers, are highly selective against many malignancies and can bypass certain challenging therapeutic resistance mechanisms. Photosensitizers such as the small cationic molecule EtNBS (5-ethylamino-9-diethyl-aminobenzo[a]phenothiazinium chloride) have proven potent against cancer cells that reside within acidic and hypoxic tumour microenvironments. At higher doses, however, these photosensitizers induce “dark toxicity” through light-independent mechanisms. In this study, we evaluated the use of nanoparticle encapsulation to overcome this limitation. Interestingly, encapsulation of the compound within poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-EtNBS) was found to significantly reduce EtNBS dark toxicity while completely retaining the molecule’s cytotoxicity in both normoxic and hypoxic conditions. This dual effect can be attributed to the mechanism of release: EtNBS remains encapsulated until external light irradiation, which stimulates an oxygen-independent, radical-mediated process that degrades the PLGA nanoparticles and releases the molecule. As these PLGA-encapsulated EtNBS nanoparticles are capable of penetrating deeply into the hypoxic and acidic cores of 3D spheroid cultures, they may enable the safe and efficacious treatment of otherwise unresponsive tumour regions.

Figure S1, schematic concept of the three-dimensional dark-field microscopy imaging setup; Figure S2, dynamic light scattering measurement of anti-CA125 and anti-Biotin antibody-conjugated 80 nm spherical gold plasmonic nanoparticles (PNPs); Figure S3, dynamic light scattering measurement and UV-visible absorption spectra of anti-CA125 and anti-Biotin antibody-conjugated PNPs treated with various concentrations of CA125 antigen; Figure S4, color quantization for monomer, dimer, and trimer based on the red/ green intensity ratios (R/G ratios); Figure S5, mathematical model for evaluating the systemic error of the color quantization method for bound PNPs in MUC16 binding on the surface of the cell; Figure S6, PNP-based digital cytometric assay on ovarian cancer cells (OVCAR3) with and without centrifugation; Figure S7, optimization of incubation conditions for the ratio of treated PNPs to cells in the PNP-based digital cytometric assay on ovarian cancer cells (OVCAR3); Figure S8, cell membrane mask generated by a deep convolutional neural network (U-Net) to exclude unbound PNPs nearby the cells in the enumeration of bound PNPs on the surface of cells; Figure S9, longitudinal study of bound MUC16/CA125 on the surface of EOC patient's PBMCs over a 17 month period at 1 month intervals; Figure S10, evaluation of the specific binding ability of anti-CA125 PNPs toward its targets on the patient's and healthy subject's PBMCs with various PBMC to PNP ratios; Figure S11, dark-field microscopy image montages of anti-CA125 PNPs bound to individual PBMCs in samples from five healthy donors and five serous invasive EOC patients; Figure S12, flow cytometric analysis for the evaluation of bound MUC16 on the surface of PBMCs from five healthy donors and five serous invasive ovarian cancer patients; Figure S13, scanning electron microscopy images of OVCAR3 clone treated with antibody-conjugated PNPs; and Table S1, ages and the CA125 levels in the serum of healthy donors and ovarian cancer patients (PDF)

Inflammation involves a cascade of cellular and molecular mediators that ultimately lead to the infiltration of immune cells into the affected area. This inflammatory process in skin is common to many diseases including acne, infection, and psoriasis, with the presence or absence of immune cells a potential diagnostic marker. Here we show that skin inflammation can be non-invasively measured and mapped using a paint-on oxygen sensing bandage in an in vivo porcine inflammation model. After injection of a known inflammatory agent, the bandage could track the increase, plateau, and decrease in oxygen consumption at the injury site over 7 weeks, as well as discern inflammation resultant from injection at various depths beneath the surface of the skin. Both the initial rate of pO 2 change and the change in bandage pO 2 at equilibration (CBP 20 ) were found to be directly related to the metabolic oxygen consumption rate of the tissue in contact. Healthy skin demonstrated an initial pO 2 decrease rate of 6.5 , and a larger CBP 20 of 140 mmHg . The change in the bandage pO 2 before and after equilibration with tissue was found to correlate well with histological evidence of skin inflammation in the animals. Birngruber, G. Apiou-Sbirlea, R. Matyal, T. Huang, R. Chan, S. J. Lin, and C. L. Evans, "Non-invasive transdermal two-dimensional mapping of cutaneous oxygenation with a rapid-drying liquid bandage," Biomed.