Advancing Medical Applications of Cancer Nanotechnology: Highlighting Two Decades of the NCI'S Nanotechnology Characterization Laboratory Service to the Research Community.

The Nanotechnology Characterization Laboratory (NCL) is a US federally funded resource providing characterization and expertise to the cancer nanomedicine research community. Founded as a formal partnership among the US National Cancer Institute (NCI), the US Food and Drug Administration (FDA), and the US National Institute of Standards and Technology (NIST), the NCL has spent two decades developing a one-of-a-kind service with broad multidisciplinary expertise to meet the needs of a rapidly evolving drug development field. To mark the 20th anniversary of the lab's founding, the NCL hosted a symposium to highlight the achievements of the cancer nanomedicine field, showcase novel, next-generation nanotechnology research, and discuss future priorities to enable continued growth in combating cancer and the complexities associated with treating a disease that continues to take millions of lives annually.

Cellular fate of a plant virus immunotherapy candidate.

Cowpea mosaic virus (CPMV) is a plant virus that is currently being developed for intratumoral immunotherapy. CPMV relieves the immune system from tumor-induced immunosuppression; reprograms the tumor microenvironment to an activated state whereby the treated and distant tumors are recognized and eradicated. Toward translational studies, we investigated the safety of CPMV, specifically addressing whether pathogenicity would be induced in mammalian cells.

Current state of nanomedicine drug products: An industry perspective.

Nanomedicine drug products have reached an unprecedented high in terms of global commercial acceptance and media exposure with the approvals of the mRNA COVID-19 vaccines in 2021. In this paper, we examine the current state of the art for nanomedicine technologies as applied for pharmaceutical products and compare those trends with results from a recent IQ Consortium industry survey on nanomedicine drug products. We find that 1) industry companies continue to push the envelope in terms of new technologies for characterizing their specific drug products, 2) new analytical technologies continue to be utilized by industry to characterize the increasingly complex nanomedicine drug products and 3) alignment and communication are key between industry and regulatory authorities to better understand the regulatory filings that are being submitted.

Nano-mupirocin as tumor-targeted antibiotic: Physicochemical, immunotoxicological and pharmacokinetic characterization, and effect on gut microbiome.

Nano-mupirocin is a PEGylated nano-liposomal formulation of the antibiotic mupirocin, undergoing evaluation for treating infectious diseases and intratumor bacteria. Intratumoral microbiota play an important role in the regulation of tumor progression and therapeutic efficacy. However, antibiotic use to target intratumoral bacteria should be performed in a way that will not affect the gut microbiota, found to enable the efficacy of cancer treatments.

A Static Headspace Gas Chromatography Method for Quantitation of Residual Solvents in Nanoformulations.

Various organic solvents are widely used in the manufacturing, processing, and purification of drug substances, drug products, formulations, excipients, etc. These solvents must be removed to the lowest amount permitted, as they do not possess any therapeutic advantages and may cause undesirable toxicities. Therefore, a rapid and sensitive analytical method for the quantitation of residual solvents is needed.

Ion Quantitation in Liposomal Products Using RP-HPLC with Charged Aerosol Detection.

Ion concentration in liposomal drugs is important for drug stability and drug release profile. However, quantifying ion concentration in liposomal drugs is challenging due to the absence of chromophores or fluorophores of ions and the efficiency of their release from the liposome structure. To address these issues, a method based on reversed-phase high-performance liquid chromatography (RP-HPLC) coupled with a charged aerosol detector (CAD) has been developed to determine total, internal, and external ions in drug-loaded liposomal products.

Measuring Size and Number Concentration of Metallic Nanoparticles Using spICP-MS.

This protocol describes how to measure the size and concentration of individual metallic nanoparticles using inductively coupled plasma-mass spectrometry (ICP-MS) in single-particle (sp) mode. Accurately determining the size of individual nanoparticles on a per-particle basis, both quickly and accurately, is an ever-increasing need within nanoparticle characterization. ICP-MS is capable of measuring a broad range of metallic nanoparticle sizes with high resolution, thus allowing the measurement of multiple particle populations for the quality assessment of nanoformulations.

Particle Size and Concentration Measurement Using the Spectradyne nCS1 Instrument.

This protocol describes the use of the Spectradyne nCS1 instrument to measure the particles per mL concentration and size of nanoparticles. The Spectradyne nCS1 is a particle-analyzing instrument that uses microfluidic resistive pulse sensing, rather than optical measurements, to determine the size and concentration of samples. The size and concentration of a sample are determined by measuring the changes in voltage as particles travel through a nano-constriction in the microfluidic cartridge.

Quantitation of Active Pharmaceutical Ingredients in Polymeric Drug Products Using Elemental Analysis.

Polymeric prodrugs have gained significant popularity as a strategy to enhance the bioavailability and improve the pharmacokinetic properties of active pharmaceutical ingredients (API). Since the amount of the API in a polymeric prodrug product directly impacts both safety and efficacy, there is a pressing need for robust and accurate analytical methods to quantify the API in these formulations. Presently, drug quantification methods include reversed-phase high-performance liquid chromatography (RP-HPLC) and size exclusion chromatography (SEC)-based molecular weight determination.

Assessment of Protein Binding Using Asymmetric-Flow Field-Flow Fractionation Combined with Multi-angle Light Scattering and Dynamic Light Scattering.

Asymmetric-flow field-flow fractionation (AF4) is a valuable tool to separate and assess different size populations in nanotherapeutics. When coupled with both static light scattering and dynamic light scattering, it can be used to qualitatively assess protein binding to nanoparticles by comparing the shape factors for both non-plasma-incubated samples and plasma-incubated samples. The shape factor is defined as the ratio of the derived root mean square radius (by static light scattering) to the measured hydrodynamic radius (by dynamic light scattering).

Nanoparticle Size Distribution and Stability Assessment Using Asymmetric-Flow Field-Flow Fractionation.

Nanomaterials are inherently polydisperse. Traditional techniques, such as the widely used batch-mode dynamic light-scattering (DLS) analysis, are not ideal nor thoroughly descriptive enough to define the full complexity of these materials. Asymmetric-flow field-flow fractionation (AF4) with various in-line detectors, such as ultraviolet-visible (UV-vis), multi-angle light scattering (MALS), refractive index (RI), and DLS, is an alternative technique that can provide flow-mode analysis of not only size distribution but also shape, drug release/stability, and protein binding.

Advancements in Nanoparticle Characterization.

Nanotechnology for drug delivery has made significant advancements over the last two decades. Innovations have been made in cancer research and development, including chemotherapies, imaging agents, and vaccine strategies, as well as other therapeutic areas, e.g.

Multicolor flow cytometry-based immunophenotyping for preclinical characterization of nanotechnology-based formulations: an insight into structure activity relationship and nanoparticle biocompatibility profiles.

Introduction: Immunophenotyping, which is the identification of immune cell subsets based on antigen expression, is an integral technique used to determine changes of cell composition and activation in various disease states or as a response to different stimuli. As nanoparticles are increasingly utilized for diagnostic and therapeutic applications, it is important to develop methodology that allows for the evaluation of their immunological impact. Therefore, the development of techniques such as immunophenotyping are desirable.

Change in Lipofectamine Carrier as a Tool to Fine-Tune Immunostimulation of Nucleic Acid Nanoparticles.

Nucleic acid nanoparticles (NANPs) require a carrier to allow for their intracellular delivery to immune cells. Cytokine production, specifically type I and III interferons, allows for reliable monitoring of the carrier effect on NANP immunostimulation. Recent studies have shown that changes in the delivery platform (e.

Trends and patterns in cancer nanotechnology research: A survey of NCI's caNanoLab and nanotechnology characterization laboratory.

Cancer nanotechnologies possess immense potential as therapeutic and diagnostic treatment modalities and have undergone significant and rapid advancement in recent years. With this emergence, the complexities of data standards in the field are on the rise. Data sharing and reanalysis is essential to more fully utilize this complex, interdisciplinary information to answer research questions, promote the technologies, optimize use of funding, and maximize the return on scientific investments.