Biomimetic Nanohybrids for Combined imaging and Cancer Therapy
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Biomimetic Nanohybrids for Combined imaging and Cancer Therapy A. Topete1, P. Iglesias2, M. Alatorre-Meda1, A. Cambón1, E. Alvarez1, J. A. Costoya2, S. Barbosa1, P. Taboada1*, V. Mosquera1 1 Grupo de Física de Coloides y Polímeros; and 2Grupo de Oncología Molecular, Universidad de Santiago de Compostela, 15782, Santiago de Compostela, Spain. ABSTRACT In this work, we have developed a multifunctional theranostic nanoplatform consisting of a poly(lactic-co-glycolic acid) (PLGA) biodegradable matrix covered by a gold shell, which provides the system with NIR absorption ability and subsequent generation of hyperthermia effect. Inside the PLGA nanoparticle, the chemotherapeutic drug doxorubicin (DOXO) and the NIR dye isocyanine green (ICG) were loaded. The characterization of the particles, their in vitro cytotocixity combining NIR light irradiation and chemotherapy and their preliminary in vivo biodistribution is analyzed. INTRODUCTION One of the areas of nanotechnology that has captured the interest of researchers worldwide is the development of nanoengineered multifunctional systems which could be simultaneously used for the treatment and diagnosis of diseases, the so-called nanotheranostic devices.1 Nanoengineering of materials for this purpose involves the design, fabrication and testing of systems that must combine several features such as biocompatibility, stealthness, longcirculating blood times, drug transpot ability, triggerable drug release, imaging detection capabilities, targetability amongst others. Improvement and suitable conjunction of all these characteristics would allow the early diagnosis of cancer and other diseases, the significant reduction in the therapeutic drug doses, or the simultaneous combination of several therapeutic treatments with a monitorization in real time to check their effectiveness. The combination of hyperthermia by using NIR absorbing plasmonic materials such metallic nanostructures, and chemotherapy is an encouraging approach for cancer treatment, which results in synergistic cytotoxic effects that are greater than the two treatments alone.2 By the integration of the advantages of NIR optical imaging capabilities, then avoiding the autofluorescence of body tissues to a nanodevice with the former therapeutic capabilities, a fully developed theranostic system would be created. Following this approach, we have developed a multifunctional nanoplatform consisting of a poly(lactic-co-glycolic acid) (PLGA) biodegradable matrix covered by a gold shell, which provides the system with NIR absorption ability and subsequent generation of hyperthermia effect. Inside the PLGA nanoparticle, the chemotherapeutic drug doxorubicin (DOXO) and the near-infrared (NIR) dye isocyanine green (ICG) were loaded, the latter being the only NIR dye approved by FDA for medical diagnosis3, and widely used for angiography and for evaluation of cardiac output and hepatic function.4 The present nanoconstruct display several similarities with previously synthesized gold-shell-coated PLGA NPs 5-7, although the la
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