Antibody-Conjugated Polymersomes with Encapsulated Indocyanine Green J-Aggregates and High Near-Infrared Absorption for Molecular Photoacoustic Cancer Imaging.

Imaging plays a critical role in all stages of cancer care from early detection to diagnosis, prognosis, and therapy monitoring. Recently, photoacoustic imaging (PAI) has started to emerge into the clinical realm due to its high sensitivity and ability to penetrate tissues up to several centimeters deep. Herein, we encapsulated indocyanine green J (ICGJ) aggregate, one of the only FDA-approved organic exogenous contrast agents that absorbs in the near-infrared range, at high loadings up to ∼40% w/w within biodegradable polymersomes (ICGJ-Ps) composed of poly(lactide-co-glycolide-b-polyethylene glycol) (PLGA-b-PEG). The small Ps hydrodynamic diameter of 80 nm is advantageous for in vivo applications, while directional conjugation with epidermal growth factor receptor (EGFR) targeting cetuximab antibodies renders molecular specificity. Even when exposed to serum, the ∼11 nm-thick membrane of the Ps prevents dissociation of the encapsulated ICGJ for at least 48 h with a high ratio of ICGJ to monomeric ICG absorbances (i.e., I895/I780 ratio) of approximately 5.0 that enables generation of a strong NIR photoacoustic (PA) signal. The PA signal of polymersome-labeled breast cancer cells is proportional to the level of cellular EGFR expression, indicating the feasibility of molecular PAI with antibody-conjugated ICGJ-Ps. Furthermore, the labeled cells were successfully detected with PAI in highly turbid tissue-mimicking phantoms up to a depth of 5 mm with the PA signal proportional to the amount of cells. These data show the potential of molecular PAI with ICGJ-Ps for clinical applications such as tumor margin detection, evaluation of lymph nodes for the presence of micrometastasis, and laparoscopic imaging procedures.

Supercritical carbon dioxide extraction of Usnea longissima (L.) Ach.: Optimization by Box-Behnken design (BBD).

Usnic acid (UA) was extracted from Usnea longissima (L.) Ach. in supercritical carbon dioxide (SC-CO2) medium. The selected process parameters were extraction temperature (35-45 °C), amount of co-solvent (0%-5%) and extraction time (5-9 h). These parameters were applied to Box-Behnken design (BBD) belonging to response surface methodology (RSM) to determine optimum process parameters for the highest amount of UA in the extract. g UA/100g lichen, extraction yield % and UA content values were calculated in the range of 0.045-0.317, 2.77-5.4 and 71%-82% in different experimental conditions, respectively. The optimum conditions were predicted as 42 °C, 4.3% (ethanol) and 7.48 h. It was determined that the predicted and experimental values of g UA/100g lichen were compatible, and the suggested model was valid.

Experimental and Modelling Analysis of the Hyperthermia Properties of Iron Oxide Nanocubes.

The ability of magnetic nanoparticles (MNPs) to transform electromagnetic energy into heat is widely exploited in well-known thermal cancer therapies, such as magnetic hyperthermia, which proves useful in enhancing the radio- and chemo-sensitivity of human tumor cells. Since the heat release is ruled by the complex magnetic behavior of MNPs, a careful investigation is needed to understand the role of their intrinsic (composition, size and shape) and collective (aggregation state) properties. Here, the influence of geometrical parameters and aggregation on the specific loss power (SLP) is analyzed through in-depth structural, morphological, magnetic and thermometric characterizations supported by micromagnetic and heat transfer simulations. To this aim, different samples of cubic Fe3O4 NPs with an average size between 15 nm and 160 nm are prepared via hydrothermal route. For the analyzed samples, the magnetic behavior and heating properties result to be basically determined by the magnetic single- or multi-domain configuration and by the competition between magnetocrystalline and shape anisotropies. This is clarified by micromagnetic simulations, which enable us to also elucidate the role of magnetostatic interactions associated with locally strong aggregation.

Synthesis and characterization of Fe3O4-MPTMS-PLGA nanocomposites for anticancer drug loading and release studies.

Magnetic nanocomposites (Fe3O4-MPTMS-PLGA) were synthesized by single oil emulsion method and characterized by transmission electron microscopy (TEM), X-Ray diffraction (XRD), and vibrating sample magnetometer (VSM). Particle size of nanocomposites was between 117 nm and 246 nm. High performance liquid chromatography (HPLC) was used to investigate drug loading (paclitaxel, PTX) and release from Fe3O4-MPTMS-PLGA-PTX nanocomposites. The percentages of drug loading and encapsulation efficiency onto nanocomposites were found as 7.35 and 68.58, respectively. Cytotoxities of free anticancer drug and anticancer drug-loaded nanocomposites were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. In vitro cell culture studies indicated that Fe3O4-MPTMS-PLGA-PTX had significant toxicity on MG-63 cancer cells.