Abstract

In most of the cases, the diagnostic and therapy stages are carried out independently and this lead todelays in the application of the treatments and, therefore, an important risk to the patients´ health. Toovercome these incoveniences, in the few last years theranostic has reached an important role to joinin a unique nanoplatform therapeutic treatment, action and monitoring of the response to simultaneoustherapy. Thus, we designed an hybrid nanosystems based on gold nanoparticles capable ofsimultaneously combining their potential as a photodynamic therapeutic agent (PDT), plasmonicphotothermal therapy (PPTT) and/or chemotherapy to kill malignant cells. In order to do that,gold nanorods (GNR) were functionalized by the layer-by-layer (LbL) assembly technique usingalternate layers of polyelectrolytes (PE): poly (styrene sulfonate) (PSS) and poly-L-lysine (PLL) asanionically and cationically charged polymeric layers, and an outer layer of hyaluronic acid (HA) toprovide the hybrid particles with sufficient colloidal stability and steering ability. Doxorrubicin(DOXO) and SiRNA were added by electrostatic interactions to the PSS and PLL layers for providingchemo- and genetic therapy, respectively, controlling the % weight and encapsulated efficiency ofdoxorubicin and SiRNA with their calibration curve. To provide the PDT capabilities to thenanoplatform, the green indocyanine photosensitizer (ICG) was previously conjugated to the PLLpolymer and assembled into the nanoplatform by electrostatic interactions, checking its efficiencywith the fluorometer. In this way, hybrid particles formed by GNR coated with PSS/DOXO/PLL @ICG@SiRNA / HA layers were obtained, in which the therapeutic PDT activity of the dye ICG,chemo- activity of DOXO and the photothermal properties of the plasmonic metal nanoparticles canbe simultaneously be applied for efficient cancer therapeutics. Nanoplatforms were characterizated byUV-Vis, FTIR and RAMAN spectroscopy, -potential and TEM. In addition, PPTT therapy of thenanoplatforms was evaluated at different irradiation powers. Finally, single oxygen ( 1 O 2 ) productionunder NIR light excitation by the hybrid nanosystem was evaluated in vitro at several powerintensities by means of fluorescence and absorbance spectroscopies and fluorescent microscopy.

Highlights

  • In the few last years theranostic has reached an important role to join in a unique nanoplatform therapeutic treatment, action and monitoring of the response to simultaneous therapy

  • We designed an hybrid nanosystems based on gold nanoparticles capable of simultaneously combining their potential as a photodynamic therapeutic agent (PDT), plasmonic photothermal therapy (PPTT) and/or chemotherapy to kill malignant cells [1–9]

  • Hybrid particles formed by gold nanorods (GNR) coated with PSS/DOXO/PLL @ ICG@SiRNA/hyaluronic acid (HA) layers were obtained, in which the therapeutic PDT activity of the dye ICG, chemoactivity of DOXO and the photothermal properties of the plasmonic metal nanoparticles can be simultaneously be applied for efficient cancer therapeutics

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Summary

Introduction

In most of the cases, the diagnostic and therapy stages are carried out independently and this lead to delays in the application of the treatments and, an important risk to the patients’ health. In the few last years theranostic has reached an important role to join in a unique nanoplatform therapeutic treatment, action and monitoring of the response to simultaneous therapy.

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