Folate-targeted Pluronic-chitosan nanocapsules loaded with IR780 for near-infrared fluorescence imaging and photothermal-photodynamic therapy of ovarian cancer.

Herein, we report the fabrication of a nanotherapeutic platform integrating near-infrared (NIR) imaging with combined therapeutic potential through photodynamic (PDT) and photothermal therapies (PTT) and recognition functionality against ovarian cancer. Owing to its NIR fluorescence, singlet oxygen generation and heating capacity, IR780 iodide is exploited to construct a multifunctional nanosystem for single-wavelength NIR laser imaging-assisted dual-modal phototherapy. We opted for loading IR780 into polymeric Pluronic-F127-chitosan nanoformulation in order to overcome its hydrophobicity and toxicity and to allow functionalization with folic acid. The obtained nanocapsules show temperature-dependent swelling and spectroscopic behavior with favorable size distribution for cellular uptake at physiological temperatures, improved fluorescence properties and good stability. The fabricated nanocapsules can efficiently generate singlet oxygen in solution and are able to produce considerable temperature increase (46 °C) upon NIR laser irradiation. Viability assays on NIH-OVCAR-3 cells confirm the successful biocompatibilization of IR780 by encapsulating in Pluronic and chitosan polymers. NIR fluorescence imaging assays reveal the ability of folic-acid functionalized nanocapsules to serve as intracellular contrast agents and demonstrate their active targeting capacity against folate receptor expressing ovarian cancer cells (NIH-OVCAR-3). Consequently, the targeted nanocapsules show improved NIR laser induced phototherapeutic performance against NIH-OVCAR-3 cells compared to free IR780. We anticipate that this class of nanocapsules holds great promise as theranostic agents for application in image-guided dual PDT-PTT and imaging assisted surgery of ovarian cancer.

Biosynthesis of silver nanoparticles using Sambucus nigra L. fruit extract for targeting cell death in oral dysplastic cells.

The study aims to evaluate the impact of silver nanoparticles, phytosynthesized with polyphenols from Sambucus nigra L. (SN) fruit extract (AgSN), on dysplastic oral keratinocytes (DOK) and human gingival fibroblasts (HGF) in terms of cell viability and apoptosis. The morphology and ultrastructure of treated cells as well as the mechanisms involved in cell death induction were investigated in DOK cultures. The structure of AgSN was studied by using the appropriate analysis tools such as UV-Vis, transmission electron microscopy, Raman spectroscopy, dynamic light scattering (DLS) and zeta potential assessment. DOK and HGF were treated either with silver nanoparticles capped with Sambucus nigra L. extract or with SN extract. Untreated cells were used as controls. Viability was determined by MTS assay. Transmission electronic microscopy (TEM) was used to evaluate the intracellular localization of the nanoparticles at 4 and 24 h. Annexin V-FITC/propidium iodide staining and the expressions of p53, BAX, BCL2, NFkB, phosphorylated NFkB (pNFkB), pan AKT, pan phosphoAKT, LC3B and É£H2AX were evaluated to quantify the cell death. ELISA measurements of TNF-α and TRAIL was used for the study of the inflammatory response. Oxidative stress damage induced by nanoparticles was assessed by the malondialdehyde (MDA) level. Silver nanoparticles stimulated HGF proliferation and significantly diminished DOK viability at doses higher than 20 µg/ml. TEM analysis demonstrated the internalization of silver nanoparticles and showed ultrastructural changes of cells such as the appearance of vacuoles, autophagosomes, endosomes. AgSN inhibited the pro-survival molecules and regulators of apoptosis, diminished oxidative stress and inflammation and induced cell death through various mechanisms: necrosis, autophagy and DNA lesions. SN extract had antioxidant and anti-inflammatory effect and increased the DNA lesions and autophagy in DOK cells. Silver nanoparticles protected the normal cells and induced cell death in dysplastic cells by different mechanisms thus offering beneficial effects in the treatment of oral dysplasia.

Efficient combined near-infrared-triggered therapy: Phototherapy over chemotherapy in chitosan-reduced graphene oxide-IR820 dye-doxorubicin nanoplatforms.

Significant efforts are currently being funneled into the improvement of therapeutic outcomes in cancer by designing hybrid nanomaterials that synergistically combine chemotherapeutic abilities and near-infrared (NIR) light-activated photothermal (PTT) and photodynamic (PDT) activity. Herein, a nanotherapeutic platform is specifically designed to integrate combinational functionalities: chemotherapy, PTT, PDT and traceable optical properties. The system, based on chitosan-reduced graphene oxide (chit-rGO), incorporates and carries a large payload of IR820 dye with dual PTT and PDT activity and a chemotherapeutic drug, doxorubicin (DOX). The potential of the fabricated nanoplatforms to operate as an NIR activatable therapeutic agent is first assessed in aqueous solution by investigating its ability to generate singlet oxygen and heat under NIR irradiation with 785 nm laser irradiation. The in vitro anticancer activity of chit-rGO-IR820-DOX is evaluated against murine colon carcinoma cells (C26). The fabricated nanosystem exhibits synergistic anticancer activity against C26 cancer cells by combining IR820 induced PDT, simultaneous graphene and IR820 induced PTT and the chemotherapeutic effect of DOX. Notably, the therapeutic performance of chit-rGO-IR820-DOX can be controlled by the ratio between IR820 and DOX. Moreover, chit-rGO-IR820-DOX facilitates localization inside cancer cells correlated with the release of DOX via mapping by confocal Raman microscopy.

Chitosan-coated triangular silver nanoparticles as a novel class of biocompatible, highly effective photothermal transducers for in vitro cancer cell therapy.

One of the relevant directions that nanotechnology is taking nowadays is connected with nanomedicine and specifically related to the use of light and nanoparticles in early diagnosis and effective therapeutics of cancer. Noble-metal nanoparticles can act under laser irradiation as effective photothermal transducers for triggering localized hyperthermia of tumors. In this work we report the performance of newly synthesized chitosan-coated silver nanotriangles (Chit-AgNTs) with strong resonances in near-infrared (NIR) to operate as photothermal agents against a line of human non-small lung cancer cells (NCI-H460). The hyperthermia experiments were conducted by excitation of nanoparticles-loaded cells at 800 nm wavelength from a Ti:Sapphire laser. We found that the rate of cell mortality in the presence of Chit-AgNTs is higher than in the presence of thiolated poly(ethylene) glycol capped gold nanorods (PEG-AuNRs) - a common hyperthermia agent used as reference-, while no destructive effects were noticed on the control sample (cells without nanoparticles) under identical irradiation conditions. Additionally, we conducted cytotoxicity assays and found Chit-AgNTs to be efficiently uptaken by the cells while exhibiting good biocompatibility for healthy human embryonic cells (HEK), which is essential for any in vivo applications. Our results reveal a novel class of biocompatible plasmonic nanoparticles with high potential to be implemented as effective phototherapeutic agents in the battle against cancer.