Subramanian Tamil Selvan

Functional and Multifunctional Nanoparticles for Bioimaging and Biosensing

Herein, we describe the synthesis of functional and multifunctional nanoparticles (NPs), derived from our recent work, for bioimaging and biosensing applications. The functionalized NPs involve quantum dots (QDs), magnetic particles (MPs) and noble metal NPs for the aforementioned applications. A diverse silica coating approaches (reverse microemulsion and thin silanization) are delineated for the design of water-soluble NPs. We also review the synthesis of silica-coated bifunctional NPs consisting of MPs and QDs for live cell imaging of human liver cancer cells (HepG2) and mouse fibroblast cells (NIH-3T3). Using silica coated NPs, various NPs that are functionalized with antibody, oligonucleotide, biotin and dextran are efficiently used for protein detection.

Gadolinium oxide ultranarrow nanorods as multimodal contrast agents for optical and magnetic resonance imaging.

We demonstrate a simple synthetic strategy for the fabrication of single-phase rare earth (RE) doped gadolinium oxide (Gd(2)O(3):RE where RE = terbium (Tb), ytterbium (Yb), and erbium (Er)) nanorods (NRs) as multimodal imaging probes. The NRs are ultranarrow and exhibit both emission and magnetic characteristics. The Tb-doped and Yb/Er-codoped Gd(2)O(3) NRs exhibit down- and up-conversion fluorescence respectively, and also exhibit paramagnetism. Importantly, these codoped NRs possess excellent magnetic characteristics, as shown in their longitudinal relaxation time (T1) -weighted image contrast, which is closer to that of commercial Gadovist for magnetic resonance imaging (MRI) applications. This property opens up new avenues in the development of contrast agents.

Synthesis of Tunable, Highly Luminescent QD‐Glasses Through Sol‐Gel Processing

Photostable quantum dot (QD)-glasses for use in optical devices can be prepared by solution-phase synthesis of the luminescent material followed by sol-gel processing, to embed the semiconductor particles in silica. Prevention of surface reactions that slowly quench the luminescence and degrade the QD is a key problem of their production. A solution to this was found in octylamine, which, when added during the sol-gel processing, not only passivates the surface of the QD but also accelerates the gelation process. CdSe QDs capped with ZnS thus treated remain luminescent over several months.

Multifunctional Iron Oxide Nanoparticles for Diagnostics, Therapy and Macromolecule Delivery

In recent years, multifunctional nanoparticles (NPs) consisting of either metal (e.g. Au), or magnetic NP (e.g. iron oxide) with other fluorescent components such as quantum dots (QDs) or organic dyes have been emerging as versatile candidate systems for cancer diagnosis, therapy, and macromolecule delivery such as micro ribonucleic acid (microRNA). This review intends to highlight the recent advances in the synthesis and application of multifunctional NPs (mainly iron oxide) in theranostics, an area used to combine therapeutics and diagnostics. The recent applications of NPs in miRNA delivery are also reviewed.

Bimodal magnetic-fluorescent probes for bioimaging.

Fluorescent optical probes have been intensively used in the area of bio‐imaging. In this review article, we describe the recent advancements in the synthesis and application of bimodal magnetic–fluorescent probes for bioimaging. The bimodal probes consist of fluorescent [semiconducting quantum dots (e.g., CdSe/ZnS) or rare‐earth doped (e.g., NaYF4:Yb,Er)] nanoparticles (NPs) and magnetic (iron oxide or gadolinium based) NPs for optical and magnetic resonance (MR) imaging. Microsc. Res. Tech., 2011.

Design and synthesis of polymer-functionalized NIR fluorescent dyes--magnetic nanoparticles for bioimaging.

The fluorescent probes having complete spectral separation between absorption and emission spectra (large Stokes shift) are highly useful for solar concentrators and bioimaging. In bioimaging application, NIR fluorescent dyes have a greater advantage in tissue penetration depth compared to visible-emitting organic dyes or inorganic quantum dots. Here we report the design, synthesis, and characterization of an amphiphilic polymer, poly(isobutylene-alt-maleic anhyride)-functionalized near-infrared (NIR) IR-820 dye and its conjugates with iron oxide (Fe3O4) magnetic nanoparticles (MNPs) for optical and magnetic resonance (MR) imaging. Our results demonstrate that the Stokes shift of unmodified dye can be tuned (from ~106 to 208 nm) by the functionalization of the dye with polymer and MNPs. The fabrication of bimodal probes involves (i) the synthesis of NIR fluorescent dye (IR-820 cyanine) functionalized with ethylenediamine linker in high yield, >90%, (ii) polymer conjugation to the functionalized NIR fluorescent dye, and (iii) grafting the polymer-conjugated dyes on iron oxide MNPs. The resulting uniform, small-sized (ca. 6 nm) NIR fluorescent dye-magnetic hybrid nanoparticles (NPs) exhibit a wider emissive range (800-1000 nm) and minimal cytotoxicity. Our preliminary studies demonstrate the potential utility of these NPs in bioimaging by means of direct labeling of cancerous HeLa cells via NIR fluorescence microscopy and good negative contrast enhancement in T2-weighted MR imaging of a murine model.

Interaction of stable colloidal nanoparticles with cellular membranes

Due to their ultra-small size, inorganic nanoparticles (NPs) have distinct properties compared to the bulk form. The unique characteristics of NPs are broadly exploited in biomedical sciences in order to develop various methods of targeted drug delivery, novel biosensors and new therapeutic pathways. However, relatively little is known in the negotiation of NPs with complex biological environments. Cell membranes (CMs) in eukaryotes have dynamic structures, which is a key property for cellular responses to NPs. In this review, we discuss the current knowledge of various interactions between advanced types of NPs and CMs.

MicroRNAs -the next generation therapeutic targets in human diseases.

MicroRNAs (miRNAs), an abundant class of ~22-nucleotide non-coding RNAs, regulate the expression of genes at post transcriptional level. MiRNAs are important regulators of eukaryotic gene expression and therefore implicated in a wide range of biological processes. The miRNA-related genetic alterations are possibly more implicated human diseases than currently appreciated. Genetic variants in miRNA target sites, called miRNA genes are identified to be associated with human diseases. This review discusses about the role of micro-RNA genes in various human diseases such as neurodegenerative disorders, cardio-vascular diseases, and metabolic disorders, and how they can be targeted as a new therapeutic tool in future with reference to drug discoveries/ development.

Core – shell upconversion nanoparticle – semiconductor heterostructures for photodynamic therapy

Core-shell nanoparticles (CSNPs) with diverse chemical compositions have been attracting greater attention in recent years. However, it has been a challenge to develop CSNPs with different crystal structures due to the lattice mismatch of the nanocrystals. Here we report a rational design of core-shell heterostructure consisting of NaYF4:Yb,Tm upconversion nanoparticle (UCN) as the core and ZnO semiconductor as the shell for potential application in photodynamic therapy (PDT). The core-shell architecture (confirmed by TEM and STEM) enables for improving the loading efficiency of photosensitizer (ZnO) as the semiconductor is directly coated on the UCN core. Importantly, UCN acts as a transducer to sensitize ZnO and trigger the generation of cytotoxic reactive oxygen species (ROS) to induce cancer cell death. We also present a firefly luciferase (FLuc) reporter gene based molecular biosensor (ARE-FLuc) to measure the antioxidant signaling response activated in cells during the release of ROS in response to the exposure of CSNPs under 980 nm NIR light. The breast cancer cells (MDA-MB-231 and 4T1) exposed to CSNPs showed significant release of ROS as measured by aminophenyl fluorescein (APF) and ARE-FLuc luciferase assays, and ~45% cancer cell death as measured by MTT assay, when illuminated with 980 nm NIR light.

Mimicking cellular transport mechanism in stem cells through endosomal escape of new peptide-coated quantum dots

Protein transport is an important phenomenon in biological systems. Proteins are transported via several mechanisms to reach their destined compartment of cell for its complete function. One such mechanism is the microtubule mediated protein transport. Up to now, there are no reports on synthetic systems mimicking the biological protein transport mechanism. Here we report a highly efficient method of mimicking the microtubule mediated protein transport using newly designed biotinylated peptides encompassing a microtubule-associated sequence (MTAS) and a nuclear localization signaling (NLS) sequence, and their final conjugation with streptavidin-coated CdSe/ZnS quantum dots (QDs). Our results demonstrate that these novel bio-conjugated QDs enhance the endosomal escape and promote targeted delivery into the nucleus of human mesenchymal stem cells via microtubules. Mimicking the cellular transport mechanism in stem cells is highly desirable for diagnostics, targeting and therapeutic applications, opening up new avenues in the area of drug delivery.