Many therapeutic methods existing for conventional cancer therapy have not been successful in achieving ideal outcomes or have noticeable side effects from off-targeting 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.
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.
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 with high 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.
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.
Department of Zoology, Bharathiar University, Coimbatore.
Has not received any funding.
C. Massard: Consultant/Advisory fees: Amgen, Astellas, Astra Zeneca, Bayer, BeiGene, BMS, Celgene, Debiopharm, Genentech, Ipsen, Janssen, Lilly, MedImmune, Novartis, Pfizer, Roche, Sanofi, Orion; Principal/sub-Investigator of Clinical Trials: Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Arno Therapeutics, Astex Pharmaceuticals, Astra Zeneca, Aveo, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, Bioalliance Pharma, Biontech Ag, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Ca, Celgene Corporation, Chugai Pharmaceutical Co., Clovis Oncology, Daiichi Sankyo, Debiopharm S.A., Eisai, Exelixis, Forma, Gamamabs, Genentech, Inc., Gilead Sciences, Inc, Glaxosmithkline, Glenmark Pharmaceuticals, H3 Biomedicine, Inc, Hoffmann La Roche Ag, Incyte Corporation, Innate Pharma, Iris Servier, Janssen, Kura Oncology, Kyowa Kirin Pharm, Lilly, Loxo Oncology, Lytix Biopharma As, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Millennium Pharmaceuticals, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncomed, Oncopeptides, Onyx Therapeutics, Orion Pharma, Oryzon Genomics, Pfizer, Pharma Mar, Pierre Fabre, Rigontec Gmbh, Roche, Sanofi Aventis, Sierra Oncology, Taiho Pharma, Tesaro, Inc, Tioma Therapeutics, Inc., Xencor; Research Grants: Astrazeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Non-financial support (drug supplied): Astrazeneca, Bayer, BMS, Boringher Ingelheim, Johnson & Johnson, Lilly, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. All other authors have declared no conflicts of interest.