Nanotechnology-Based Diagnostics and Therapy for Pathogen-Related Infections in the CNS.

The central nervous system (CNS) encompasses the brain, spinal cord, and nerves, where both brain and spinal cord are safeguarded by the meninges. However, serious bacterial, viral, or fungal infection in the brain causes life-threatening diseases such as meningitis. Engineered nanostructures hold great promise for not only in the diagnosis but also for combating microbial drug resistance owing to their high surface area and innate antibacterial activity. We delineate several nanoparticle-based approaches to enhance the CNS delivery of drugs across the blood-brain barrier (BBB). While pathogens invade the CNS by phagocytosis or receptor (e.g., EphA2)-mediated transcytosis, most of the nanoparticles cross the BBB via receptor-mediated transcytosis (e.g., antibody, peptide, protein). We also provide our perspectives on the diagnostic pathways based on nanotechnology for the detection of pathogens in the brain, thereby opening up new therapeutic avenues.

Theranostic applications of nanoparticles in neurodegenerative disorders.

The preeminent treatments for neurodegenerative disease are often unavailable due to the poor accessibility of therapeutic drugs. Moreover, the blood-brain barrier (BBB) effectively blocks the transfer of cells, particles and large molecules, ie, drugs, across the brain. The most important challenge in the treatment of neurodegenerative diseases is the development of targeted drug delivery system. Theranostic strategies are known to combine therapeutic and diagnostic capabilities together. The aim of this review was to record the response to treatment and thereby improve drug safety. Nanotechnology offers a platform for designing and developing theranostic agents that can be used as an efficient nano-carrier system. This is achieved by the manipulation of some of the properties of nanoparticles (NPs), thereby enabling the attachment of suitable drugs onto their surface. The results provide revolutionary treatments by stimulation and thus interaction with targeted sites to promote physiological response with minimum side effects. This review is a brief discussion of the administration of drugs across the brain and the advantages of using NPs as an effective theranostic platform in the treatment of Alzheimer's, Parkinson's, epilepsy and Huntington's disease.

Recent progress in nanotechnology for stem cell differentiation, labeling, tracking and therapy.

Stem cells offer great potential for regenerative medicine due to their excellent capability to differentiate into a specialized cell type of the human body. Recently, nanomaterial based scaffolds (e.g. graphene), biodegradable polymers (e.g. PLGA: poly-d,l-lactic-co-glycolic acid), and inorganic nanoparticles (NPs, e.g. metallic, magnetic, upconversion) have made considerable advances in controlling the differentiation of stem cells. Some of the notable advances include the development of a variety of NPs such as gold, silica, selenium and graphene quantum dots (QDs) for the controlled differentiation of stem cells - human mesenchymal stem cells (hMSCs), and magnetic core-shell NPs (e.g. ZnFe2O4-Au) for the control of neural stem cells (NSCs). Multimodal imaging (MR, optical, ultrasound, photoacoustic) of stem cells provides opportunities for probing the fate of implanted cells, thereby determining the therapeutic efficacy. Novel multifunctional NPs have been developed over the years, and probed using the aforementioned imaging techniques for stem cell research. This review article underscores the recent progress in nanotechnology for stem cell differentiation, labeling, tracking and therapy. Nano/biomaterial assisted stem cell therapies for bone, heart, and liver regeneration are also delineated.

Supramolecular nanoparticle carriers self-assembled from cyclodextrin- and adamantane-functionalized polyacrylates for tumor-targeted drug delivery.

The advancement of nanobiotechnology has led to the development of various techniques for addressing target-specific drug delivery issues. In this article, we successfully developed a supramolecular self-assembly approach for the fabrication of polyacrylate-based nanoparticles with simultaneous loading of the anticancer drug doxorubicin (DOX) for targeted delivery towards cancer treatment in vitro and in vivo. Two types of polyacrylates functionalized with adamantane and ß-cyclodextrin respectively could self-assemble to form supramolecular nanoparticles through strong host-guest complexation between adamantane and ß-cyclodextrin. Folic acid was incorporated within the supramolecular nanoparticles in order to impart the targeting specificity towards selected cancerous cell lines, namely MDA-MB231 and B16-F10. The as-synthesized supramolecular nanoparticles were fully characterized by several techniques, revealing an average nanoparticle size of 35 nm in diameter, which is small enough for excellent blood circulation. The cytotoxicity studies indicate that the supramolecular nanoparticles without drug loading were non-cytotoxic under the concentrations measured, while DOX-loaded supramolecular nanoparticles showed significant cytotoxicity. In order to investigate the targeting specificity of DOX-loaded supramolecular nanoparticles towards the cancerous cells, a healthy cell line model HEK293 was employed for carrying out the comparison studies. Due to the presence of the targeting ligand, experimental results demonstrate that the supramolecular nanoparticles were highly specific for targeting the cancerous cells, but not for HEK293 cells. After the in vitro investigations, the in vivo drug delivery study using DOX-loaded supramolecular nanoparticles was performed. Tumor-bearing nude mice were treated with DOX-loaded supramolecular nanoparticles, and the analysis results indicate that DOX-loaded supramolecular nanoparticles have the capability to enhance the therapeutic effects of DOX for effectively inhibiting the tumor growth. Thus, the self-assembled polymeric nanoparticles exhibit a highly promising potential to serve as drug carriers for targeted drug delivery towards improved cancer treatment.

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.

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.