Nanotechnology-aided advancement in the combating of cancer metastasis.

Cancer, especially when it has metastasized to different locations in the body, is notoriously difficult to treat. Metastatic cancer accounts for most cancer deaths and thus remains an enormous challenge. During the metastasis process, cancer cells negotiate a series of steps termed the "metastatic cascadeË® that offer potential for developing anti-metastatic therapy strategies. Currently available conventional treatment and diagnostic methods addressing metastasis come with their own pitfalls and roadblocks. In this contribution, we comprehensively discuss the potential improvements that nanotechnology-aided approaches are able to bring, either alone or in combination with the existing conventional techniques, to the identification and treatment of metastatic disease. We tie specific nanotechnology-aided strategies to the complex biology of the different steps of the metastatic cascade in order to open up new avenues for fine-tuned targeting and development of anti-metastatic agents designed specifically to prevent or mitigate the metastatic outgrowth of cancer. We also present a viewpoint on the progress of translation of nanotechnology into cancer metastasis patient care.

NCI Alliance for Nanotechnology in Cancer - from academic research to clinical interventions.

The National Cancer Institute (NCI) of National Institutes of Health has funded and operated the NCI Alliance for Nanotechnology in Cancer - a large multi-disciplinary program which leverages research at the intersection of molecular biology, oncology, physics, chemistry, and engineering to develop innovative cancer interventions. The program has demonstrated that convergence of several scientific disciplines catalyzes innovation and progress in cancer nanotechnology and advances its clinical translation. This paper takes a look at last thirteen years of the Alliance program operations and delineates its outcomes, successes, and outlook for the future.

Nanotechnologies in cancer treatment and diagnosis.

Despite significant efforts toward research and treatment development, cancer continues to be a major health problem in the United States that is only further enhanced by the heterogeneous nature of the disease. Nanotechnology has evolved as a technology with applications to medicine and the potential to improve clinical outcomes, with its application to cancer garnering much attention recently. In particular, through the generation of novel nanoscale devices and therapeutic platforms, nanotechnologies have emerged as innovative approaches that enable the detection and diagnosis of cancer at its earliest stages, and the delivery of anticancer drugs directly to tumors. This article highlights recent advances in the development of nanotechnologies for cancer therapeutics and diagnostics, and focuses on the potential future of cancer nanotechnology and the challenges this young field faces as it continues to move toward clinical translation.

Current landscape of treating different cancers using nanomedicines: Trends and perspectives.

The efforts to use novel nanotechnologies in medicine and cancer have been widespread. In order to understand better the focus areas of cancer nanomedicine research to date, we conducted a survey of nanomedicine developmental and clinical research in conjunction with treatment of various cancers. The survey has been performed based on number of publications, rate of citations, entry into clinical trials, and funding rates by the National Cancer Institute. Our survey indicates that breast and brain cancers are the most and one of the least studied by nanotechnology researchers, respectively. Breast cancer nano-therapies seem to also be most likely to achieve clinical translation as the number of publications produced, amount of funding, total citations, and clinical trials (active and completed) are the highest when compared with research in other cancers. Brain cancer, despite its low survival, has capture much less attention of nanomedicine research community as survey indicated, although nanotechnology can offer novel approaches which can address brain cancer challenges. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Nanotechnology Tools Enabling Biological Discovery.

Over the years, the engineering aspect of nanotechnology has been significantly exploited. Medical intervention strategies have been developed by leveraging existing molecular biology knowledge and combining it with nanotechnology tools to improve outcomes. However, little attention has been paid to harnessing the strengths of nanotechnology as a biological discovery tool. Fundamental understanding of controlling dynamic biological processes at the subcellular level is key to developing personalized therapeutic and diagnostic interventions. Single-cell analyses using intravital microscopy, expansion microscopy, and microfluidic-based platforms have been helping to better understand cell heterogeneity in healthy and diseased cells, a major challenge in oncology. Also, single-cell analysis has revealed critical signaling pathways and biological intracellular components with key biological functions. The physical manipulation enabled by nanotools can allow real-time monitoring of biological changes at a single-cell level by sampling intracellular fluid from the same cell. The formation of intercellular highways by nanotube-like structures has important clinical implications such as metastasis development. The integration of nanomaterials into optical and molecular imaging techniques has rendered valuable morphological, structural, and biological information. Nanoscale imaging unravels mechanisms of temporality by enabling the visualization of nanoscale dynamics never observed or measured between individual cells with standard biological techniques. The exceptional sensitivity of nanozymes, artificial enzymes, make them perfect components of the next-generation mobile diagnostics devices. Here, we highlight these impactful cancer-related biological discoveries enabled by nanotechnology and producing a paradigm shift in cancer research and oncology.

Merging data curation and machine learning to improve nanomedicines.

Nanomedicine design is often a trial-and-error process, and the optimization of formulations and in vivo properties requires tremendous benchwork. To expedite the nanomedicine research progress, data science is steadily gaining importance in the field of nanomedicine. Recently, efforts have explored the potential to predict nanomaterials synthesis and biological behaviors via advanced data analytics. Machine learning algorithms process large datasets to understand and predict various material properties in nanomedicine synthesis, pharmacologic parameters, and efficacy. "Big data" approaches may enable even larger advances, especially if researchers capitalize on data curation methods. However, the concomitant use of data curation processes needed to facilitate the acquisition and standardization of large, heterogeneous data sets, to support advanced data analytics methods such as machine learning has yet to be leveraged. Currently, data curation and data analytics areas of nanotechnology-focused data science, or 'nanoinformatics', have been proceeding largely independently. This review highlights the current efforts in both areas and the potential opportunities for coordination to advance the capabilities of data analytics in nanomedicine.

Critical review of nucleic acid nanotechnology to identify gaps and inform a strategy for accelerated clinical translation.

With numerous recent advances, the field of therapeutic nucleic acid nanotechnology is now poised for clinical translation supported by several examples of FDA-approved nucleic acid nanoformulations including two recent mRNA-based COVID-19 vaccines. Within this rapidly growing field, a new subclass of nucleic acid therapeutics called nucleic acid nanoparticles (NANPs) has emerged in recent years, which offers several unique properties distinguishing it from traditional therapeutic nucleic acids. Key unique aspects of NANPs include their well-defined 3D structure, their tunable multivalent architectures, and their ability to incorporate conditional activations of therapeutic targeting and release functions that enable diagnosis and therapy of cancer, regulation of blood coagulation disorders, as well as the development of novel vaccines, immunotherapies, and gene therapies. However, non-consolidated research developments of this highly interdisciplinary field create crucial barriers that must be overcome in order to impact a broader range of clinical indications. Forming a consortium framework for nucleic acid nanotechnology would prioritize and consolidate translational efforts, offer several unifying solutions to expedite their transition from bench-to-bedside, and potentially decrease the socio-economic burden on patients for a range of conditions. Herein, we review the unique properties of NANPs in the context of therapeutic applications and discuss their associated translational challenges.

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. In order to support this, various data-sharing portals and repositories have been developed which not only provide searchable nanomaterial characterization data, but also provide access to standardized protocols for synthesis and characterization of nanomaterials as well as cutting-edge publications. The National Cancer Institute's (NCI) caNanoLab is a dedicated repository for all aspects pertaining to cancer-related nanotechnology data. The searchable database provides a unique opportunity for data mining and the use of artificial intelligence and machine learning, which aims to be an essential arm of future research studies, potentially speeding the design and optimization of next-generation therapies. It also provides an opportunity to track the latest trends and patterns in nanomedicine research. This manuscript provides the first look at such trends extracted from caNanoLab and compares these to similar metrics from the NCI's Nanotechnology Characterization Laboratory, a laboratory providing preclinical characterization of cancer nanotechnologies to researchers around the globe. Together, these analyses provide insight into the emerging interests of the research community and rise of promising nanoparticle technologies.

Nanotechnology-based cancer therapeutics--promise and challenge--lessons learned through the NCI Alliance for Nanotechnology in Cancer.

The new generation of nanotechnology-based drug formulations is challenging the accepted ways of cancer treatment. Multi-functional nanomaterial constructs have the capability to be delivered directly to the tumor site and eradicate cancer cells selectively, while sparing healthy cells. Tailoring of the nano-construct design can result in enhanced drug efficacy at lower doses as compared to free drug treatment, wider therapeutic window, and lower side effects. Nanoparticle carriers can also address several drug delivery problems which could not be effectively solved in the past and include reduction of multi-drug resistance effects, delivery of siRNA, and penetration of the blood-brain-barrier. Although challenges in understanding toxicity, biodistribution, and paving an effective regulatory path must be met, nanoscale devices carry a formidable promise to change ways cancer is diagnosed and treated. This article summarizes current developments in nanotechnology-based drug delivery and discusses path forward in this field. The discussion is done in context of research and development occurring within the NCI Alliance for Nanotechnology in Cancer program.

Nanotechnology for Cancer Imaging: Advances, Challenges, and Clinical Opportunities.

Nanoparticle (NP) imaging applications have the potential to improve cancer diagnostics, therapeutics, and treatment management. In biomedical research and clinical practice, NPs can serve as labels or labeled carriers for monitoring drug delivery or serve as imaging agents for enhanced imaging contrast, as well as providing improved signal sensitivity and specificity for in vivo imaging of molecular and cellular processes. These qualities offer exciting opportunities for NP-based imaging agents to address current limitations in oncologic imaging. Despite substantial advancements in NP design and development, very few NP-based imaging agents have translated into clinics within the past 5 years. This review highlights some promising NP-enabled imaging techniques and their potential to address current clinical cancer imaging limitations. Although most examples provided herein are from the preclinical space, discussed imaging solutions could offer unique in vivo tools to solve biologic questions, improve cancer treatment effectiveness, and inspire clinical translation innovation to improve patient care. Keywords: Molecular Imaging-Cancer, Molecular Imaging-Nanoparticles, Molecular Imaging-Optical Imaging, Metastases, Oncology, Surgery, Treatment Effects.

Nanomaterials innovation as an enabler for effective cancer interventions.

Nanomedicines have been developing very rapidly and have started to play a significant role in several cancer therapeutic modalities. Early on, the nanomedicine field focused on optimizing pharmacokinetics, toxicity, and/or biodistribution of an agent through nanoparticle formulation. In other cases, where materials science is employed more decisively, nanomedicine can include the creation of new agents that take advantage of nanoscale materials properties to enhance treatment efficacy through unique mode of action, molecular targeting, or controlled drug release. Both current and future nanomedicines will seek to contribute to the therapeutic and diagnostic landscape through creative leveraging of mechanical, electrical, optical, magnetic, and biological nanomaterial properties. In this work, we discuss how by modulating these material properties, one can design more diverse and more effective cancer interventions. We focus on six areas in cancer management, including in vitro diagnostics, clinical imaging, theranostics, combination therapy, immunotherapy, and gene therapy.

National Cancer Institute Alliance for nanotechnology in cancer-Catalyzing research and translation toward novel cancer diagnostics and therapeutics.

Nanotechnology has been a burgeoning research field, which is finding compelling applications in several practical areas of everyday life. It has provided novel, paradigm shifting solutions to medical problems and particularly to cancer. In order to accelerate integration of nanotechnology into cancer research and oncology, the National Cancer Institute (NCI) of the National Institutes of Health (NIH) established the NCI Alliance for Nanotechnology in Cancer program in 2005. This effort brought together scientists representing physical sciences, chemistry, and engineering working at the nanoscale with biologists and clinicians working on cancer to form a uniquely multidisciplinary cancer nanotechnology research community. The last 14 years of the program have produced a remarkable body of scientific discovery and demonstrated its utility to the development of practical cancer interventions. This paper takes stock of how the Alliance program influenced melding of disparate research disciplines into the field of nanomedicine and cancer nanotechnology, has been highly productive in the scientific arena, and produced a mechanism of seamless transfer of novel technologies developed in academia to the clinical and commercial space. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging.

Integrating Nanotechnology into Cancer Care.

Research activity in medical and cancer nanotechnology has grown dramatically over the past 15 years. The field has become a cradle of multidisciplinary investigations bringing together physicists, chemists, and engineers working with clinicians and biologists to address paramount problems in cancer care and treatment. Some have argued that the explosion in the number of research papers has not been followed by sufficient clinical activity in nanomedicine. However, three new nanodrugs have now been approved by the U.S. Food and Drug Administration (FDA) in the past three years, confirming the validity of nanotechnology approaches in cancer. Excitingly, translational pipelines contain several additional intriguing candidates. In this Nano Focus article, we discuss potential barriers inhibiting further incorporation of nanomedicines into patient care, possible strategies to overcome these barriers, and promising new directions in cancer interventions based on nanotechnology. Insights presented herein are outcomes of discussions held at a recent strategic workshop hosted by the National Cancer Institute (NCI), which brought together research, clinical, and commercial leaders of the nanomedicine field.

Big Potential from Small Agents: Nanoparticles for Imaging-Based Companion Diagnostics.

The importance of medical imaging in the diagnosis and monitoring of cancer cannot be overstated. As personalized cancer treatments are gaining popularity, a need for more advanced imaging techniques has grown significantly. Nanoparticles are uniquely suited to fill this void, not only as imaging contrast agents but also as companion diagnostics. This review provides an overview of many ways nanoparticle imaging agents have contributed to cancer imaging, both preclinically and in the clinic, as well as charting future directions in companion diagnostics. We conclude that, while nanoparticle-based imaging agents are not without considerable scientific and developmental challenges, they enable enhanced imaging in nearly every modality, hold potential as in vivo companion diagnostics, and offer precise cancer treatment and maximize intervention efficacy.

Nanotechnology Strategies To Advance Outcomes in Clinical Cancer Care.

Ongoing research into the application of nanotechnology for cancer treatment and diagnosis has demonstrated its advantages within contemporary oncology as well as its intrinsic limitations. The National Cancer Institute publishes the Cancer Nanotechnology Plan every 5 years since 2005. The most recent iteration helped codify the ongoing basic and translational efforts of the field and displayed its breadth with several evolving areas. From merely a technological perspective, this field has seen tremendous growth and success. However, an incomplete understanding of human cancer biology persists relative to the application of nanoscale materials within contemporary oncology. As such, this review presents several evolving areas in cancer nanotechnology in order to identify key clinical and biological challenges that need to be addressed to improve patient outcomes. From this clinical perspective, a sampling of the nano-enabled solutions attempting to overcome barriers faced by traditional therapeutics and diagnostics in the clinical setting are discussed. Finally, a strategic outlook of the future is discussed to highlight the need for next-generation cancer nanotechnology tools designed to address critical gaps in clinical cancer care.

Nanobiotechnology: the promise and reality of new approaches to molecular recognition.

Nanobiotechnology is the convergence of engineering and molecular biology that is leading to a new class of multifunctional devices and systems for biological and chemical analysis with better sensitivity and specificity and a higher rate of recognition. Nano-objects with important analytical applications include nanotubes, nanochannels, nanoparticles, nanopores and nanocapacitors. Here, we take a critical look at the subset of recent developments in this area relevant to molecular recognition. Potential benefits of using nano-objects (nanotubes, quantum dots, nanorods and nanoprisms) and nanodevices (nanocapacitors, nanopores and nanocantilevers) leading to an expanded range of label multiplexing are described along with potential applications in future diagnostics. We also speculate on further pathways in nanotechnology development and the emergence of order in this somewhat chaotic, yet promising, new field.

NCI investment in nanotechnology: achievements and challenges for the future.

Nanotechnology offers an exceptional and unique opportunity for developing a new generation of tools addressing persistent challenges to progress in cancer research and clinical care. The National Cancer Institute (NCI) recognizes this potential, which is why it invests roughly $150 M per year in nanobiotechnology training, research and development. By exploiting the various capacities of nanomaterials, the range of nanoscale vectors and probes potentially available suggests much is possible for precisely investigating, manipulating, and targeting the mechanisms of cancer across the full spectrum of research and clinical care. NCI has played a key role among federal R&D agencies in recognizing early the value of nanobiotechnology in medicine and committing to its development as well as providing training support for new investigators in the field. These investments have allowed many in the research community to pursue breakthrough capabilities that have already yielded broad benefits. Presented here is an overview of how NCI has made these investments with some consideration of how it will continue to work with this research community to pursue paradigm-changing innovations that offer relief from the burdens of cancer.

Cell-to-cell communication in cancer: workshop report.

Recent advances in cancer biology and the development of new research tools have enabled interrogations of single cells and cell-cell interactions. Emerging technologies are capable of revealing data on the physical characteristics of cells, differences in the genome and proteome between cancerous and healthy cells, and variations in distinct cell subpopulations. Dynamic measurements enable studies that can reveal the evolution of cell characteristics. Cells can also be assembled in vitro or ex vivo into two- and three-dimensional cell environments, allowing for studies of cell-cell interactions and cell signaling. The Memorial Sloan Kettering Cancer Center, in collaboration with the Breast Cancer Research Foundation and the National Cancer Institute, co-organized a workshop as an opportunity for leading researchers in their respective fields to present and discuss scientific research highlights relevant to the utilization of techniques and technologies for studying cell-to-cell communications in cancer. Avenues of future development and the potential for clinical utility were primary features of these discussions. The scientific presentations and extensive ensuing discussions resulted in the identification of a number of research opportunities, which are summarized in this report.

Bubble-induced acoustic micromixing.

A mixing technique based on the principle of bubble-induced acoustic microstreaming was developed. The mixer consists of a piezoelectric disk that is attached to a reaction chamber, which is designed in such a way that a set of air bubbles with desirable size is trapped in the solution. Fluidic experiments showed that air bubbles resting on a solid surface and set into vibration by the sound field generated steady circulatory flows, resulting in global convection flows and thus rapid mixing. The time to fully mix a 22 microL chamber is significantly reduced from hours (for a pure diffusion-based mixing) to tens of seconds. Numerical simulations showed that the induced flowfield and thus degree of mixing strongly depend on bubble positions. Optimal simulated mixing results were obtained for staggered bubble distribution that minimizes the number of internal flow stagnation regions. Immunomagnetic cell capture experiments showed that acoustic microstreaming provided efficient mixing of bacterial cell (Esherichia coli K12) matrix suspended in blood with magnetic capture beads, resulting in highly effective immunomagnetic cell capture. Bacterial viability assay experiments showed that acoustic microstreaming has a relatively low shear strain field since the blood cells and bacteria remained intact after mixing. Acoustic microstreaming has many advantages over most existing chamber micromixing techniques, including simple apparatus, ease of implementation, low power consumption (2 mW), and low cost.