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.

Improved pharmacokinetics and reduced side effects of doxorubicin therapy by liposomal co-encapsulation with curcumin.

The goal of the current study was to investigate the pharmacokinetic profile, tissue distribution and adverse effects of long-circulating liposomes (LCL) with curcumin (CURC) and doxorubicin (DOX), in order to provide further evidence for previously demonstrated enhanced antitumor efficacy in colon cancer models. The pharmacokinetic studies were carried out in healthy rats, following the i.v. injection of a single dose of LCL-CURC-DOX (1 mg/kg DOX). For the tissue distribution study, DOX concentration in tumours, heart and liver were measured after the administration of two i.v. doses of LCL-CURC-DOX (2.5 mg/kg DOX and 5 mg/kg CURC) to Balb/c mice bearing C26 colon tumours. Markers of murine cardiac and hepatic oxidative status were determined to provide additional insights into the benefit of co-encapsulating CURC and DOX in LCL over DOX-induced adverse effects in these organs. The current study demonstrated that the liposomal association of CURC and DOX effectively improved the pharmacokinetics and biodistribution of DOX, limiting its side effects, via CURC-dependent antioxidant effects.

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.