Folic Acid-Conjugated, SERS-Labeled Silver Nanotriangles for Multimodal Detection and Targeted Photothermal Treatment on Human Ovarian Cancer Cells

The effectiveness of a therapeutic agent for cancer stands in its ability to reduce and eliminate tumors without harming the healthy tissue nearby. Nanoparticles peripherally conjugated with targeting moieties offer major improvements in therapeutics through site specificity. In this study we demonstrate this approach by targeting the folate receptor of NIH:OVCAR-3 human ovary cancer cell line. Herein we used silver nanotriangles which were biocompatibilized with chitosan (bio)­polymer, labeled with para-aminothiophenol (pATP) Raman reporter molecule, and conjugated with folic acid. The nanoparticles conjugation and efficient labeling was investigated by localized surface plasmon resonance (LSPR), zeta potential, and surface-enhanced Raman scattering (SERS) measurements. Conjugated particles were proven to be highly stable in aqueous and cellular medium. The targeted uptake of conjugated nanoparticles by human ovary cancer cells was confirmed by dark field microscopy and scattering spectra of the particles inside cells. Comparative studies revealed specific internalization of the conjugated nanoparticles in comparison with similar bare nanoparticles. Moreover, the SERS identity of the particles was proven to be highly conserved inside cells. Targeted cancer cell treatment conducted by irradiating the nanoparticle-treated cells with a continuous wave-nearinfrared (cw-NIR) laser in resonance with their plasmonic band proved an efficient therapeutic response. By integrating the advantages of multimodal optical imaging and SERS detection with hyperthermia capabilities through site specificity, these nanoparticles can represent a real candidate for personalized medicine

Additional file 1: of Design of FLT3 Inhibitor - Gold Nanoparticle Conjugates as Potential Therapeutic Agents for the Treatment of Acute Myeloid Leukemia

Figure SF1. Nanoparticle stability test by optical spectroscopy. Figure SF2. Absorption spectra of supernatants from drug-release assay. Figure SF3. Optical response of GNP-MDS-Pl after release. Table SF1. Statistical analysis for the cell proliferation for OCI-AML3 cell line. Table SF2. Statistical analysis for the cell proliferation for THP1cell line

Designing Theranostic Agents Based on Pluronic Stabilized Gold Nanoaggregates Loaded with Methylene Blue for Multimodal Cell Imaging and Enhanced Photodynamic Therapy

At present, multifunctional noble metal-based nanocomposites are extensively investigated for their potential in performing cellular imaging, diagnostics, and therapy by integration of unique plasmonic properties with the spectroscopic expression and therapeutic activity of appropriate drug. In this work, we report the fabrication of 3-dimensional (3-D) close-packed nanoassemblies of gold nanoparticles by controlling the aggregation of individual nanoparticles in solution and subsequent stabilization of formed aggregates by Pluronic block copolymer (F127) coating. Besides conferring high stability, Pluronic mediates the loading of Methylene Blue (MB) molecules which exhibit interesting spectroscopic and photochemical properties to be employed as both optical label and photosensitizing drug. Indeed, here we demonstrate the pertinence of the fabricated nanoassemblies to provide optical imaging of murine colon carcinoma cells (C-26) via both Raman and fluorescence signals collected from MB molecules, specifically by using scanning confocal surface-enhanced resonant raman spectroscopy (SERRS) and fluorescence lifetime imaging microscopy (FLIM) techniques. The specific configuration of as fabricated nanoassemblies allows a small population of MB molecules to be located in very small areas between the aggregated nanoparticles (“hot spots”) to provide SERRS signal while the other population remains captured in Pluronic coating and preserves both its fluorescence signal and singlet-oxygen generation capability. Remarkably, we demonstrate an enhanced photodynamic therapeutic activity of MB-loaded gold nanoaggregates against murine colon carcinoma cells (C-26), as compared to the free photosensitizer. To our knowledge, this is the first report on plasmonic nanoplatforms conveying photosensitizing drug into cells to operate as optical label via both SER­(R)S and FLIM and to perform enhanced photodynamic therapy