Enhanced antigen presentation and immunostimulation of dendritic cells using acid-degradable cationic nanoparticles.

Acid-degradable cationic nanoparticles encapsulating a model antigen (i.e., ovalbumin) were prepared by inverse microemulsion polymerization with acid-cleavable acetal cross-linkers. Incubation of these degradable nanoparticles with dendritic cells derived from bone marrow (BMDCs) resulted in the enhanced presentation of ovalbumin-derived peptides, as quantified by B3Z cells, a CD8+ T cell hybridoma. The cationic nature of the particles contributed to the increased surface endocytosis (or phagocytosis) observed with BMDCs, which is the first barrier to overcome for successful antigen delivery. The acid sensitivity of the particles served to direct more ovalbumin antigens to be processed into the appropriately trimmed peptide fragments and presented via the major histocompatibility complex (MHC) class I pathway following hydrolysis within the acidic lysosomes. It was also shown that adjuvant molecules such as unmethylated CpG oligonucleotides (CpG ODN) and anti-interleukin-10 oligonucleotides (AS10 ODN) could be co-delivered with the protein antigen for maximized cellular immune response

Efficient and facile delivery of gold nanoparticles in vivo using dissolvable microneedles for contrast-enhanced optical coherence tomography

Obtaining sufficient contrast is an indispensable requirement for detecting early stage cancer using optical coherence tomography (OCT), an emerging diagnostic tool that detects abnormal lesions with micrometer resolutions in real time. PEGylated gold nanoparticles (Au NPs; 87 nm in diameter) were formulated in aqueous dissolvable microneedles (dMNs; 200 μm height) for efficient, precisely controlled, and convenient delivery of Au NPs into hamster oral tissue in vivo. The Au NPs were then further briefly dissipated by ultrasound (US). The results showed 33% and 20% increase in average optical scattering intensity (contrast level) in dysplastic and normal tissues, respectively, and pinpointed pathological structures of early stage oral cancer were also identified by the highly convenient and efficient administration of Au NPs in a novel delivery platform

Preparation and Quantification of Pseudotyped Retroviral Vector

Retroviral vectors have been widely used for research and clinical trials in gene therapy because of their high transduction efficiency. Retroviruses interact with target cells through their surface molecules (i.e., envelope proteins) and cellular receptors, which limit the susceptibility of target cells to retroviral vectors. Murine leukemia retrovirus (MuLV) pseudotyped with vesicular stomatitis virus G glycoprotein (VSV-G) overcomes the species barrier and is more resistant to mechanical and biochemical inactivation. A cell line producing VSV-G pseudotyped MuLV vector can be established by transfecting 293T cells expressing Gag, Pol, and VSV-G (293 GPG cell line) with a retroviral vector plasmid. Transduction potency of the resulting VSV-G pseudotyped MuLV retroviral supernatant can be quantified by titration, electron microscopy (EM), and the reverse transcriptase (RT) assay. These protocols provide methods to prepare and quantify a pseudotyped retroviral vector with high transduction rates for most types of target cells

Cancer nanotechnology: current status and perspectives.

Modern medicine has been waging a war on cancer for nearly a century with no tangible end in sight. Cancer treatments have significantly progressed, but the need to increase specificity and decrease systemic toxicities remains. Early diagnosis holds a key to improving prognostic outlook and patient quality of life, and diagnostic tools are on the cusp of a technological revolution. Nanotechnology has steadily expanded into the reaches of cancer chemotherapy, radiotherapy, diagnostics, and imaging, demonstrating the capacity to augment each and advance patient care. Nanomaterials provide an abundance of versatility, functionality, and applications to engineer specifically targeted cancer medicine, accurate early-detection devices, robust imaging modalities, and enhanced radiotherapy adjuvants. This review provides insights into the current clinical and pre-clinical nanotechnological applications for cancer drug therapy, diagnostics, imaging, and radiation therapy

Design, challenge, and promise of stimuli-responsive nanoantibiotics.

Over the past few years, there have been calls for novel antimicrobials to combat the rise of drug-resistant bacteria. While some promising new discoveries have met this call, it is not nearly enough. The major problem is that although these new promising antimicrobials serve as a short-term solution, they lack the potential to provide a long-term solution. The conventional method of creating new antibiotics relies heavily on the discovery of an antimicrobial compound from another microbe. This paradigm of development is flawed due to the fact that microbes can easily transfer a resistant mechanism if faced with an environmental pressure. Furthermore, there has been some evidence to indicate that the environment of the microbe can provide a hint as to their virulence. Because of this, the use of materials with antimicrobial properties has been garnering interest. Nanoantibiotics, (nAbts), provide a new way to circumvent the current paradigm of antimicrobial discovery and presents a novel mechanism of attack not found in microbes yet; which may lead to a longer-term solution against drug-resistance formation. This allows for environment-specific activation and efficacy of the nAbts but may also open up and create new design methods for various applications. These nAbts provide promise, but there is still ample work to be done in their development. This review looks at possible ways of improving and optimizing nAbts by making them stimuli-responsive, then consider the challenges ahead, and industrial applications.Graphical abstractA graphic detailing how the current paradigm of antibiotic discovery can be circumvented by the use of nanoantibiotics