Green Approach: ''A Forwarding Step for Curing Leishmaniasis-A Neglected Tropical Disease''.

The present review focuses on a dreaded vector-mediated leishmaniasis, with the existing therapeutic approaches including a variety of drugs along with their limitations, the treatment with natural compounds, and different types of metal/metal oxide nanoparticles (NPs). As evidenced, various metallic NPs, comprising silver, silver oxide, gold, zinc oxide, titanium, lead oxide, etc., played a curative role to treat leishmaniasis, are also presented. Keeping in view the advance success of vaccines against the prevalent dreaded diseases in the past and the present scenario, efforts are also being made to develop vaccines based on these NP formulations.

Nanomedicine for Cystic Fibrosis.

Cystic fibrosis is a genetic disease affecting more than 70,000 people worldwide. Caused by a mutation in the CFTR gene, cystic fibrosis can result in difficulty breathing, widespread bacterial infections, edema, malnutrition, pancreatitis, and death. Current drug-based treatments struggle to reach the site of action due to the thick mucus, and only manage symptoms such as blocked airways, lung infections, and limited ability to digest food. Nanotechnology opens up possibilities for improved treatment strategies by focusing on drug penetration through the mucus lining, eliminating resulting bacterial infections, and targeting the underlying genetic cause of the disease. In this review, we present recent nanoparticle developments for cystic fibrosis, challenges in nanomedicine therapeutics, and future research directions in gene editing and nonviral vectors for gene delivery.

Pancreatic Cancer Gene Therapy Delivered by Nanoparticles.

Pancreatic cancer is one of the most lethal forms of cancer and has proven to be difficult to treat through conventional methods, including surgery and chemotherapy. Gene therapy serves as a potential novel treatment to interfere with genes that make this cancer so aggressive, but free nucleic acids have low cell uptake due to their negative charge and are unstable in circulation. Nanoparticles can serve as an effective carrier for a wide variety of gene therapies for pancreatic cancer as they can improve the circulation time, decrease the recognition by the immune system, and be functionalized to target specific surface proteins. In this review, we focus on therapeutic strategies using nanoparticles as carriers of small interfering RNA (siRNA), microRNA (miRNA), and gene augmentation (DNA) therapies in the context of pancreatic cancer. Lastly, we discuss the future outlook of nanoparticle-based therapies, including challenges in the clinical setting.

Theranostic Nanoparticles for Tracking and Monitoring Disease State.

The development of novel nanoparticles consisting of both diagnostic and therapeutic components has increased over the past decade. These "theranostic" nanoparticles have been tailored toward one or more types of imaging modalities and have been developed for optical imaging, magnetic resonance imaging, ultrasound, computed tomography, and nuclear imaging comprising both single-photon computed tomography and positron emission tomography. In this review, we focus on state-of-the-art theranostic nanoparticles that are capable of both delivering therapy and self-reporting/tracking disease through imaging. We discuss challenges and the opportunity to rapidly adjust treatment for individualized medicine.

Digital Assays Part II: Digital Protein and Cell Assays.

A digital assay is one in which the sample is partitioned into many containers such that each partition contains a discrete number of biological entities (0, 1, 2, 3, . . .). A powerful technique in the biologist's toolkit, digital assays bring a new level of precision in quantifying nucleic acids, measuring proteins and their enzymatic activity, and probing single-cell genotype and phenotype. Where part I of this review focused on the fundamentals of partitioning and digital PCR, part II turns its attention to digital protein and cell assays. Digital enzyme assays measure the kinetics of single proteins with enzymatic activity. Digital enzyme-linked immunoassays (ELISAs) quantify antigenic proteins with 2 to 3 log lower detection limit than conventional ELISA, making them well suited for low-abundance biomarkers. Digital cell assays probe single-cell genotype and phenotype, including gene expression, intracellular and surface proteins, metabolic activity, cytotoxicity, and transcriptomes (scRNA-seq). These methods exploit partitioning to 1) isolate single cells or proteins, 2) detect their activity via enzymatic amplification, and 3) tag them individually by coencapsulating them with molecular barcodes. When scaled, digital assays reveal stochastic differences between proteins or cells within a population, a key to understanding biological heterogeneity. This review is intended to give a broad perspective to scientists interested in adopting digital assays into their workflows.

Digital Assays Part I: Partitioning Statistics and Digital PCR.

A digital assay is one in which the sample is partitioned into many small containers such that each partition contains a discrete number of biological entities (0, 1, 2, 3, …). A powerful technique in the biologist's toolkit, digital assays bring a new level of precision in quantifying nucleic acids, measuring proteins and their enzymatic activity, and probing single-cell genotypes and phenotypes. Part I of this review begins with the benefits and Poisson statistics of partitioning, including sources of error. The remainder focuses on digital PCR (dPCR) for quantification of nucleic acids. We discuss five commercial instruments that partition samples into physically isolated chambers (cdPCR) or droplet emulsions (ddPCR). We compare the strengths of dPCR (absolute quantitation, precision, and ability to detect rare or mutant targets) with those of its predecessor, quantitative real-time PCR (dynamic range, larger sample volumes, and throughput). Lastly, we describe several promising applications of dPCR, including copy number variation, quantitation of circulating tumor DNA and viral load, RNA/miRNA quantitation with reverse transcription dPCR, and library preparation for next-generation sequencing. This review is intended to give a broad perspective to scientists interested in adopting digital assays into their workflows. Part II focuses on digital protein and cell assays.

Nanobiotech in big pharma: a business perspective.

Since the early 2000s, numerous publications have presented major scientific opportunities that can be achieved through integrating insights from the area of nanotech into biotech (nanobiotech). This paper aims to explore the economic significance that nanobiotech has gained in the established pharmaceutical industry (big pharma). The empirical investigation draws on patent data as well as product revenue data; and to put the results into perspective, the amounts are compared with the established/traditional biotech sector. The results indicate that the new technology still plays only a minor role - at least from a commercial perspective.

Direct Nuclear Delivery of DNA by Photothermal Nanoblade.

We demonstrate direct nuclear delivery of DNA into live mammalian cells using the photothermal nanoblade. Pulsed laser-triggered cavitation bubbles on a titanium-coated micropipette tip punctured both cellular plasma and nuclear membranes, which was followed by pressure-controlled delivery of DNA into the nucleus. High-level and efficient plasmid expression in different cell types with maintained cell viability was achieved.

Microengineered vascular systems for drug development.

Recent advances in microfabrication technologies and advanced biomaterials have allowed for the development of in vitro platforms that recapitulate more physiologically relevant cellular components and function. Microengineered vascular systems are of particular importance for the efficient assessment of drug candidates to physiological barriers lining microvessels. This review highlights advances in the development of microengineered vascular structures with an emphasis on the potential impact on drug delivery studies. Specifically, this article examines the development of models for the study of drug delivery to the central nervous system and cardiovascular system. We also discuss current challenges and future prospects of the development of microengineered vascular systems.