Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics.

The United States Food and Drug Administration has permitted number of therapeutic agents for cancer treatment. Most of them are expensive and have some degree of systemic toxicity which makes overbearing in clinical settings. Although advanced research continuously applied in cancer therapeutics, but drug resistance, metastasis, and recurrence remain unanswerable. These accounts to an urgent clinical need to discover natural compounds with precisely safe and highly efficient for the cancer prevention and cancer therapy. Gambogic acid (GA) is the principle bioactive and caged xanthone component, a brownish gamboge resin secreted from the of Garcinia hanburyi tree. This molecule showed a spectrum of biological and clinical benefits against various cancers. In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent. This review also delineates specific molecular mechanism(s) of GA that are involved in anti-cancer, anti-metastasis, anti-angiogenesis, and chemo-/radiation sensitizer activities. Furthermore, recent evidence, development, and implementation of various nanoformulations of gambogic acid (nanomedicine) have been described.

The solid progress of nanomedicine.

This commentary article conveys the views of the board of the Nanomedicine and Nanoscale Delivery Focus Group of the Controlled Release Society regarding the decision of the United States National Cancer Institute (NCI) in halting funding for the Centers of Cancer Nanotechnology Excellence (CCNEs), and the subsequent editorial articles that broadened this discussion. Graphical abstract.

Perspectives on the Future of Nanomedicine to Impact Patients: An Analysis of US Federal Funding and Interventional Clinical Trials.

The US and governments around the world, and companies, have made a considerable investment in nanomedicine, and there have been important discoveries. Nevertheless, there has been considerable debate as to whether the investment, both in money and in time, has been worth it. That question is not yet definitively answerable. However, investigators (and investors) might also wonder if the efforts in nanomedicine are likely to continue at the same pace as over the past decade. For this paper, an analysis was done by searching Medline, RePORT, the DOD (CDMRP), the NSF, and ClinicalTrials.gov. The major findings from the analysis are as follows: (1) The number of journal articles on the subject of nanomedicine continues to steadily rise and the areas "Drug Carriers" and "Drug Delivery Systems" are experiencing particularly rapid growth. (2) The level of funding from the Department of Health and Human Services (NIH and others) for indications other than cancer has been greater than that for cancer. (3) Funding for applications in HIV/AIDS has been strong. (4) Most of the cancers are being impacted. (5) The number of clinical trials are more highly focused in breast, skin, metastatic, and ovarian cancers, though the noncancer indications of pain and infections are also highly represented. The trials are primarily in Phases I and II, suggesting a long horizon before translating to a high impact on patients. (6) The vast majority of the clinical trials are for the evaluation of established nanomedicine formulations (liposomes and nab-paclitaxel/Abraxane) in combination with other therapies. Nevertheless, the number of clinical trials with other nanomedicine formulations has been increasing since 2009. Relatively few of the trials are for micelles or dendrimers. Taken as a whole, the analysis provides a picture that nanomedicine continues to be highly funded and highly studied but with few recent breakthroughs. Nanomedicine has yet to provide the "silver bullet" for therapy in cancer or other diseases, and it remains unclear whether it ever will.

Analysis of inequality in nanomedicine using clinical trials and disease burden.

Aim: This study explores the impact nanomedicine will have on global health, poverty and inequality. Materials & methods: Using a nanotechnology search strategy, the team extracted nanotechnology clinical trials (CT) from the dataset clinicaltrials.gov. The team then combined CT with information about burden of disease data from the Institute of Health Metrics and Evaluation. Finally, the team ran regression analyses to determine whether nanotechnology CT are decreasing inequality compared with non-nanotechnology CT. Results & conclusion: Nanomedicine and non-nanomedicine CT follow similar research patterns. In general, nanomedicine is neither increasing nor decreasing the technological gap between countries in the global North and South.

Comprehensive Evaluation of Degradable and Cost-Effective Plasmonic Nanoshells for Localized Photothermolysis of Cancer Cells.

Integrating the concept of biodegradation and light-triggered localized therapy in a functional nanoformulation is the current approach in onco-nanomedicine. Morphology control with an enhanced photothermal response, minimal toxicity, and X-ray attenuation of polymer-based nanoparticles is a critical concern for image-guided photothermal therapy. Herein, we describe the simple design of cost-effective and degradable polycaprolactone-based plasmonic nanoshells for the integrated photothermolysis as well as localized imaging of cancer cells. The gold-deposited polycaprolactone-based plasmonic nanoshells (AuPCL NS) are synthesized in a scalable and facile way under ambient conditions. The synthesized nanoshells are monodisperse, fairly stable, and highly inert even at five times (250 µg/mL) the therapeutic concentration in a week-long test. AuPCL NS are capable of delivering standalone photothermal therapy for the complete ablation of cancer cells without using any anticancerous drugs and causing toxicity. It delivers the same therapeutic efficacy to different cancer cell lines, irrespective of their chemorefractory status and also works as a potential computed tomography contrast agent for the integrated imaging-directed photothermal cancer therapy. High biocompatibility, degradability, and promising photothermal efficacy of AuPCL NS are attractive aspects of this report that could open new horizons of localized plasmonic photothermal therapy for healthcare applications.

Progress in ligand design for monolayer-protected nanoparticles for nanobio interfaces.

Ligand-functionalized inorganic nanoparticles, also known as monolayer-protected nanoparticles, offer great potential as vehicles for in vivo delivery of drugs, genes, and other therapeutics. These nanoparticles offer highly customizable chemistries independent of the size, shape, and functionality imparted by the inorganic core. Their success as drug delivery agents depends on their interaction with three major classes of biomolecules: nucleic acids, proteins, and membranes. Here, the authors discuss recent advances and open questions in the field of nanoparticle ligand design for nanomedicine, with a focus on atomic-scale interactions with biomolecules. While the importance of charge and hydrophobicity of ligands for biocompatibility and cell internalization has been demonstrated, ligand length, flexibility, branchedness, and other properties also influence the properties of nanoparticles. However, a comprehensive understanding of ligand design principles lies in the cost associated with synthesizing and characterizing diverse ligand chemistries and the ability to carefully assess the structural integrity of biomolecules upon interactions with nanoparticles.

Sound understanding of environmental, health and safety, clinical, and market aspects is imperative to clinical translation of nanomedicines.

Nanotechnology has transformed materials engineering. However, despite much excitement in the scientific community, translation of nanotechnology-based developments has suffered from significant translational gaps, particularly in the field of biomedicine. Of the many concepts investigated, very few have entered routine clinical application. Safety concerns and associated socioeconomic uncertainties, together with the lack of incentives for technology transfer, are undoubtedly imposing significant hurdles to effective clinical translation of potentially game-changing developments. Commercialisation aspects are only rarely considered in the early stages and in many cases, the market is not identified early on in the process, hence precluding market-oriented development. However, methodologies and in-depth understanding of mechanistic processes existing in the environmental, health and safety (EHS) community could be leveraged to accelerate translation. Here, we discuss the most important stepping stones for (nano)medicine development along with a number of suggestions to facilitate future translation.

Emerging nanomedicine applications and manufacturing: progress and challenges.

APS 6th International PharmSci Conference 2015 7-9 September 2015 East Midlands Conference Centre, University of Nottingham, Nottingham, UK As part of the 6th APS International PharmSci Conference, a nanomedicine session was organised to address challenges and share experiences in this field. Topics ranged from the reporting on latest results and advances in the development of targeted therapeutics to the needs that the community faces in how to progress these exciting proof of concept results into products. Here we provide an overview of the discussion and highlight some of the initiatives that have recently been established to support the translation of nanomedicines into the clinic.

Soft matter assemblies as nanomedicine platforms for cancer chemotherapy: a journey from market products towards novel approaches.

The current review aims to outline the likely medical applications of nanotechnology and the potential of the emerging field of nanomedicine. Nanomedicine can be defined as the investigation area encompassing the design of diagnostics and therapeutics at the nanoscale, including nanobots, nanobiosensors, nanoparticles and other nanodevices, for the remediation, prevention and diagnosis of a variety of illnesses. The ultimate goal of nanomedicine is to improve patient quality-of-life. Because nanomedicine includes the rational design of an enormous number of nanotechnology-based products focused on miscellaneous diseases, a variety of nanomaterials can be employed. Therefore, this review will focus on recent advances in the manufacture of soft matterbased nanomedicines specifically designed to improve diagnostics and cancer chemotherapy efficacy. It will be particularly highlighted liposomes, polymer-drug conjugates, drug-loaded block copolymer micelles and biodegradable polymeric nanoparticles, emphasizing the current investigations and potential novel approaches towards overcoming the remaining challenges in the field as well as formulations that are in clinical trials and marketed products.

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.

Innovative pharmaceutical development based on unique properties of nanoscale delivery formulation.

The advent of nanotechnology has reignited interest in the field of pharmaceutical science for the development of nanomedicine. Nanomedicinal formulations are nanometer-sized carrier materials designed for increasing the drug tissue bioavailability, thereby improving the treatment of systemically applied chemotherapeutic drugs. Nanomedicine is a new approach to deliver the pharmaceuticals through different routes of administration with safer and more effective therapies compared to conventional methods. To date, various kinds of nanomaterials have been developed over the years to make delivery systems more effective for the treatment of various diseases. Even though nanomaterials have significant advantages due to their unique nanoscale properties, there are still significant challenges in the improvement and development of nanoformulations with composites and other materials. Here in this review, we highlight the nanomedicinal formulations aiming to improve the balance between the efficacy and the toxicity of therapeutic interventions through different routes of administration and how to design nanomedicine for safer and more effective ways to improve the treatment quality. We also emphasize the environmental and health prospects of nanomaterials for human health care.

Improving the translation in Europe of nanomedicines (a.k.a. drug delivery) from academia to industry.

Over the last decade the involvement of European academic scientists in the translation of Nanomedicines and Drug Delivery into useful therapeutics has been modest. Funders have become increasingly concerned and some attempts have been made in Europe to improve impact. While the consequences are minimal at present for stakeholders, the eventual impact at national and political levels could be serious and is likely to lead to reverse innovation - the import of healthcare products from developing economies - if not addressed. Some knowledge of industrial drug development is critical for innovation in this regulated sector - this information being not easily obtained outside Pharma. While peer review has failings, more important is project inception, since once started research takes on a life of its own. This paper aims to encourage healthcare researchers to take a more translational approach to selecting (applied) drug delivery projects.