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.
The synthesis and photophysical properties of two lipophilic quadrupolar chromophores featuring anthracenyl (1) or dibromobenzene (2) were described. These two chromophores combined significant two-photon absorption cross-sections with high fluorescence quantum yield for 1 and improved singlet oxygen generation efficiency for 2, in organic solvents. The use of Pluronic nanoparticles allowed a simple and straightforward introduction of these lipophilic chromophores into biological cell media. Their internal distribution in various cell lines was studied using fluorescence microscopy and flow-cytometry following a successful staining that was achieved upon 2 h of incubation. Finally, multiphoton excitation microscopy and photodynamic therapy capability of the chromophores were demonstrated by cell exposure to a 820 nm fs laser and cell death upon one photon resonant irradiation at 436 ± 10 nm, respectively.
BackgroundReleasing drug molecules at the targeted location could increase the clinical outcome of a large number of anti-tumor treatments which require low systemic damage and low side effects. Nano-carriers of drugs show great potential for such task due to their capability of accumulating and releasing their payload specifically, at the tumor site.ResultsFLT3 inhibitor - gold nanoparticle conjugates were fabricated to serve as vehicles for the delivery of anti-tumor drugs. Lestaurtinib, midostaurin, sorafenib, and quizartinib were selected among the FLT3 inhibitor drugs that are currently used in clinics for the treatment of acute myeloid leukemia. The drugs were loaded onto nanoparticle surface using a conjugation strategy based on hydrophobic-hydrophobic interactions with the Pluronic co-polymer used as nanoparticle surface coating. Optical absorption characterization of the particles in solution showed that FLT3 inhibitor-incorporated gold nanoparticles were uniformly distributed and chemically stable regardless of the drug content. Drug loading study revealed a high drug content in the case of midostaurin drug which also showed increased stability. Drug release test in simulated cancer cell conditions demonstrated more than 56 % release of the entrapped drug, a result that correlates well with the superior cytotoxicity of the nano-conjugates comparatively with the free drug.ConclusionsThis is a pioneering study regarding the efficient loading of gold nanoparticles with selected FLT3 inhibitors. In vitro cytotoxicity assessment shows that FLT3-incorporated gold nanoparticles are promising candidates as vehicles for anti-tumor drugs and demonstrate superior therapeutic effect comparatively with the bare drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s11671-015-1154-2) contains supplementary material, which is available to authorized users.
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.
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