The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.

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Minimal information for studies of extracellular vesicles 2018 (MISEV2018) : a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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Principles of nanoparticle design for overcoming biological barriers to drug delivery

Nanotechnology is a multidisciplinary field, which covers a vast and diverse array of devices derived from engineering, biology, physics and chemistry. These devices include nanovectors for the targeted delivery of anticancer drugs and imaging contrast agents. Nanowires and nanocantilever arrays are among the leading approaches under development for the early detection of precancerous and malignant lesions from biological fluids. These and other nanodevices can provide essential breakthroughs in the fight against cancer.

Cancer nanotechnology: opportunities and challenges.

The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

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Cancer nanomedicine: progress, challenges and opportunities.

This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

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Analysis of nanoparticle delivery to tumours

Long-acting tunable release of amlodipine loaded PEG-PCL micelles for tailored treatment of chronic hypertension.

Provided is a particle that includes a first porous region and a second porous region that differs from the first porous region. Also provided is a particle that has a wet etched porous region and that does have a nucleation layer associated with wet etching. Methods of making porous particles are also provided.

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Electrochemical method of making porous particles using a constant current density

Our research group was the first one to microfabricate and demonstrate nano-channels in silicon membranes (1, 2). We employed nano-channeled chips to provide immuno-isolation for cell transplantation towards the treatment of diabetes (3), for biomolecular separation (4), and for the controlled passive and active release of drug molecules from implanted capsules (5). We showed that the constraints placed upon molecular agitation in nano-channels affected their concentration-driven transport kinetics (6, 7). A zero-order passive release of biological molecules was achieved, by the rational tailoring of nano-channels dimensions. This achievement allowed releasing of a constant amount of drugs over a long period of time. However, the development and optimization of many drug therapies require long-term drug delivery with controlled but variable dosage using miniaturized systems (8). Moreover, application such as drug release from implanted devices requires tight operational control, of regulatory agency caliber. We have engaged in the development and characterization of elecroosmotic nano-channels membranes, and present our results in this communication. These include the influence of the drug release rate on nanochannel size, membrane configuration, and applied voltage.Copyright © 2010 by ASME

Electrokinetic Transport of Molecules Through Nanochanneled Membranes

As a potential source of diagnostic biomarkers for diseases at their early stage, the low-molecular weight (LMW) region of the blood proteome has gained increased interest recently. However, the presence of highly abundant proteins and the large dynamic range of serum/plasma proteins ultimately limit the sensitivity of the detection of low abundant species. In this study, we present a novel sizeexclusion strategy based on nanoporous silica chips for the efficient removal of the high molecular weight proteins and for the specific isolation and enrichment of LMW species present in biological complex. We applied the Nanoporous Silica Chip Technology at the analysis of complex proteomic samples such as human serum and developed proteomic nanochips with different nanophase characteristics to specifically target the low molecular weight species present in the human circulating peptidome. Harvested peptides were analysed by MALDI-TOF and profiles consisting of more than 300 peaks in the range 800-20,000 m/z were generated. Tunable pore sizes, pore structure and surface chemistries were used as integrated “processors” for the recovery of LMW peptides and proteins. This approach will help in the selection of individualized therapeutic combinations that target the entire cancer-specific protein network, in the real-time assessment of therapeutic efficacy and toxicity, and in the rational modulation of therapy based on changes in the cancer protein network associated with prognosis and drug resistance.

The next generation of proteomic nanochips in biomarker discovery

Tissue Engineering: Mesoporous Silicon-PLGA Composite Microspheres for the Double Controlled Release of Biomolecules for Orthopedic Tissue Engineering (Adv. Funct. Mater. 2/2012)

Xuewu Liu

Papers

Long-acting tunable release of amlodipine loaded PEG-PCL micelles for tailored treatment of chronic hypertension.

Electrochemical method of making porous particles using a constant current density

Electrokinetic Transport of Molecules Through Nanochanneled Membranes

The next generation of proteomic nanochips in biomarker discovery

Tissue Engineering: Mesoporous Silicon-PLGA Composite Microspheres for the Double Controlled Release of Biomolecules for Orthopedic Tissue Engineering (Adv. Funct. Mater. 2/2012)