Controlling the Luminescence of Carboxyl-Functionalized CdSe/ZnS Core–Shell Quantum Dots in Solution by Binding with Gold Nanorods

Plasmonic nanostructures offer promising routes toward artificial control of the photoluminescence properties of various emitters. Here, we investigated the photoluminescence of carboxyl-functionalized CdSe/ZnS core–shell quantum dots (c-QDs) localized near gold nanorods (AuNRs) as a function of c-QDs–AuNRs distance using the cetyltrimethylammonium bromide (CTAB) surfactant and Bovine Serum Albumin (BSA) protein layers over coating metal surface as spacer. The direct binding of negatively charged c-QDs to positively charged CTAB (3–4 nm thickness) caused close contact with the metal, resulting in an efficient metal-induced energy transfer (quenching). We found that quenching is modulated by the degree of spectral overlap between the photoluminescence band of c-QDs (620 nm) and longitudinal localized surface plasmon resonance (LSPR) of AuNRs (637 and 733 nm). Deposition of BSA layer over CTAB coated-AuNRs and subsequent decoration with c-QDs yielded an increase in photoluminescence signal when exciting in resonance with the transverse LSPR of AuNRs. On the basis of experimental studies using steady-state and time-resolved fluorescence measurements as well as finite-difference time-domain calculations, we report over 70% quenching efficiency for all investigated AuNRs along with a 4.6-fold in photoluminescence enhancement relative to free c-QDs (39-fold enhancement relative to c-QDs loaded AuNRs) after BSA deposition

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

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

Doxorubicin-Incorporated Nanotherapeutic Delivery System Based on Gelatin-Coated Gold Nanoparticles: Formulation, Drug Release, and Multimodal Imaging of Cellular Internalization

In this work, we developed a new pH- and temperature-responsive nanochemotherapeutic system based on Doxorubicin (DOX) noncovalently bound to biosynthesized gelatin-coated gold nanoparticles (DOX-AuNPs@gelatin). The real-time release profile of DOX was evaluated at different pH values (7.4, 5.3, and 4.6) and temperatures (22–45 °C) in aqueous solutions, and its therapeutic performance was examined <i>in vitro</i> against MCF-7 breast cancer cells. TEM, dark-field scattering, and wide-field fluorescence microscopy indicated the effective uptake of nanochemotherapeutics with the subsequent release and progressive accumulation of DOX in cell nuclei. MTT assays clearly showed the effectiveness of the treatment by inhibiting the growth of MCF-7 breast cancer cells for a loaded drug concentration of 5 μg/mL. The most informative data about the dynamic release and localization were provided by scanning confocal microscopy using time-resolved fluorescence and surface-enhanced Raman scattering (SERS) techniques. In particular, fluorescence-lifetime imaging (FLIM) recorded under 485 nm pulsed diode laser excitation revealed the bimodal distribution of DOX in cells. The shorter fluorescence lifetime of DOX localized in nuclei (1.52 ns) than in the cytoplasm (2.4 ns) is consistent with the cytotoxic mechanism induced by DOX–DNA intercalation. Remarkably, the few DOX molecules captured between nanoparticles (“electromagnetic hotspots”) after most drug is released act as SERS reporters for the localization of plasmonic nanocarriers in MCF-7 cells. The high drug loading capacity and effective drug release under pH control combined with the advantage of multimodal visualization inside cells clearly indicate the high potential of our DOX–AuNPs@gelatin delivery system for implementation in nanomedicine

Carboplatin-Loaded, Raman-Encoded, Chitosan-Coated Silver Nanotriangles as Multimodal Traceable Nanotherapeutic Delivery Systems and pH Reporters inside Human Ovarian Cancer Cells

Ovarian cancer is a common cause of cancer death in women and is associated with the highest mortality rates of all gynecological malignancies. Carboplatin (CBP) is the most used cytotoxic agent in the treatment of ovarian cancer. Herein, we design and assess a CBP nanotherapeutic delivery system which allows combinatorial functionalities of chemotherapy, pH sensing, and multimodal traceable properties inside live NIH:OVCAR-3 ovarian cancer cells. In our design, a pH-sensitive Raman reporter, 4-mercaptobenzoic acid (4MBA) is anchored onto the surface of chitosan-coated silver nanotriangles (chit-AgNTs) to generate a robust surface-enhanced Raman scattering (SERS) traceable system. To endow this nanoplatform with chemotherapeutic abilities, CBP is then loaded to 4MBA-labeled chit-AgNTs (4MBA-chit-AgNTs) core under alkaline conditions. The uptake and tracking potential of CBP-4MBA-chit-AgNTs at different <i>Z</i>-depths inside live ovarian cancer cells is evaluated by dark-field and differential interference contrast (DIC) microscopy. The ability of CBP-4MBA-chit-AgNTs to operate as near-infrared (NIR)-responsive contrast agents is validated using two noninvasive techniques: two-photon (TP)-excited fluorescence lifetime imaging microscopy (FLIM) and confocal Raman microscopy (CRM). The most informative data about the precise localization of nanocarriers inside cells correlated with intracellular pH sensing is provided by multivariate analysis of Raman spectra collected by scanning CRM. The <i>in vitro</i> cell proliferation assay clearly shows the effectiveness of the prepared nanocarriers in inhibiting the growth of NIH:OVCAR-3 cancer cells. We anticipate that this class of nanocarriers holds great promise for application in image-guided ovarian cancer chemotherapy

Spherical and Flower-Shaped Gold Nanoparticles Characterization by Scattering Correlation Spectroscopy

The aim of this study is to compare the optical scattering properties of different gold nanoparticles (GNPs), with different shapes (spherical, GNSs, and flower-shaped, GNFs), sizes (20, 30, and 50 nm), and surface chemistries (with and without PEG). These scattering properties give geometrical characterization of hydrodynamic sizes of GNPs by using the scattering correlation spectroscopy. Afterward, a multiparametric comparative study of the scattering efficiency is presented depending on various parameters such as GNPs geometry, excitation wavelength (532 and 633 nm) and powers (from 5 to 100 μW). As predicted by Mie theory, we demonstrate that the increase in GNSs size leads to an increase of the scattered intensity, proportional to the excitation power. The scattered signal is the highest when the excitation wavelength is closer to the localized surface plasmon resonance. In the case of GNFs, the measured scattered signal is around 1000 times stronger than that for GNSs of the same size and concentration. For GNFs, a scattering coefficient at the plasmon resonance of around 2 × 10^–13 m² was calculated, which is comparable to the scattering coefficient of a GNS with a diameter of 300 nm. Due to their strong scattering properties, GNFs appear as a good alternative to GNSs of the same size for cell imaging

Antibody Conjugated, Raman Tagged Hollow Gold–Silver Nanospheres for Specific Targeting and Multimodal Dark-Field/SERS/Two Photon-FLIM Imaging of CD19(+) B Lymphoblasts

In this Research Article, we propose a new class of contrast agents for the detection and multimodal imaging of CD19­(+) cancer lymphoblasts. The agents are based on NIR responsive hollow gold–silver nanospheres conjugated with antiCD19 monoclonal antibodies and marked with Nile Blue (NB) SERS active molecules (HNS-NB-PEG-antiCD19). Proof of concept experiments on specificity of the complex for the investigated cells was achieved by transmission electron microscopy (TEM). The microspectroscopic investigations via dark field (DF), surface-enhanced Raman spectroscopy (SERS), and two-photon excited fluorescence lifetime imaging microscopy (TPE-FLIM) corroborate with TEM and demonstrate successful and preferential internalization of the antibody-nanocomplex. The combination of the microspectroscopic techniques enables contrast and sensitivity that competes with more invasive and time demanding cell imaging modalities, while depth sectioning images provide real time localization of the nanoparticles in the whole cytoplasm at the entire depth of the cells. Our findings prove that HNS-NB-PEG-antiCD19 represent a promising type of new contrast agents with great possibility of being detected by multiple, non invasive, rapid and accessible microspectroscopic techniques and real applicability for specific targeting of CD19­(+) cancer cells. Such versatile nanocomplexes combine in one single platform the detection and imaging of cancer lymphoblasts by DF, SERS, and TPE-FLIM microspectroscopy