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Ponraj , T R Vivek (2019) 11P Photosensitizer-based multimodal nanocomposites as a theranostic agent for near infrared (NIR)-guided cancer-targeting synergistic chemo-phototherapy. Annals of oncology , 30. ISSN 1569-8041

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Background: Many therapeutic methods existing for conventional cancer therapy have not been successful in achieving ideal outcomes or have noticeable side effects from offtargeting cytotoxicity. The photosensitizer-based cancer treatment approach has attracted great attention. Chemotherapy (CT), photodynamic therapy (PDT), and photothermal therapy (PTT), called combination treatments. In a single system could be potential solutions to address the above mentioned adverse effects in conventional therapy. Multimodal nanocomposites (NCs) are being used to achieve with innovative and noninvasive enhanced targeting synergistic anticancer phototherapy. Methods: We prepared spherical-like titanium dioxide nanoparticles TiO2NPs by the water in oil emulsification method, obtaining a novel theranostic nanocomplex FA-ICG-Qtn@PVPylated-TiO2NPs. Nanocomplex (NCs) were characterized by various physicochemical techniques including UV via spectroscopy, TEM, DLS, FTIR, MTT, AO/EtBr, DAPI, cell cycle arrest, ROS, mitochondrial membrane potential loss, Western blot, RT-PCR, Histopathology, and immunohistochemistry. Studies were performed both in vitro/in vivo. Results: The resulting TiO2NPs achieved high drug loading in combination with low leakage at physiological pH, and minimal toxicity toward healthy cells. To assist drug delivery, we have prepared FA-ICG-Qtn@PVPylated-TiO2NPs containing Qtn withhigh loading efficiency (35.2% w/w) as a novel drug delivery system. The NCs are taken up via FR endocytosis by MCF-7 cells and can generate intracellular reactive oxygen species (ROS) in order to increase mitochondrial membrane potential loss (MMPL) and enable release of cytochrome-c, followed by dysregulation of Bcl-xL into the cytosol and activation of caspase-7 to induce cancer cell apoptosis. These NCs can be utilized to improve cancer nanotherapy by induction of apoptosis in vitro. After intravenous in vivo direction of FA-ICG-Qtn@PVPylated-TiO2NPs NCs could significantly accumulate in the tumour-bearing Balb/c mice, and effectively inhibit the tumor growth after 808 nm laser irradiation as confirmed by the cancer cell killing studies in vivo. Conclusions: The present thermal/pH-coupling controlled and targeted drug delivery system paves the way for the next generation of nanotherapeutics working toward a potential proficient targeted anticancer treatment.

Item Type: Article
Uncontrolled Keywords: cancer chemotherapy regimen photosensitizing agents phototherapy
Subjects: Cancer Research
Depositing User: Central Library RGCB
Date Deposited: 04 Jul 2019 09:54
Last Modified: 04 Jul 2019 09:55
URI: http://rgcb.sciencecentral.in/id/eprint/801

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