Developing future nanomedicines.

Quantitative analysis of biodistribution and clearance may improve nanoparticle development.

The ancillary effects of nanoparticles and their implications for nanomedicine.

Nanoparticles are often engineered as a scaffolding system to combine targeting, imaging and/or therapeutic moieties into a unitary agent. However, mostly overlooked, the nanomaterial itself interacts with biological systems exclusive of application-specific particle functionalization. This nanoparticle biointerface has been found to elicit specific biological effects, which we term 'ancillary effects'. In this Review, we describe the current state of knowledge of nanobiology gleaned from existing studies of ancillary effects with the objectives to describe the potential of nanoparticles to modulate biological effects independently of any engineered function; evaluate how these effects might be relevant for nanomedicine design and functional considerations, particularly how they might be useful to inform clinical decision-making; identify potential clinical harm that arises from adverse nanoparticle interactions with biology; and, finally, highlight the current lack of knowledge in this area as both a barrier and an incentive to the further development of nanomedicine.

Current trends and future perspectives of nanomedicine for the management of colon cancer.

Colon cancer (CC) kills countless people every year throughout the globe. It persists as one of the highly lethal diseases to be treated because the overall survival rate for CC is meagre. Early diagnosis and efficient treatments are two of the biggest hurdles in the fight against cancer. In the present work, we will review thriving strategies for CC targeted drug delivery and critically explain the most recent progressions on emerging novel nanotechnology-based drug delivery systems. Nanotechnology-based animal and human clinical trial studies targeting CC are discussed. Advancements in nanotechnology-based drug delivery systems intended to enhance cellular uptake, improved pharmacokinetics and effectiveness of anticancer drugs have facilitated the powerful targeting of specific agents for CC therapy. This review provides insight into current progress and future opportunities for nanomedicines as potential curative targets for CC treatment. This information could be used as a platform for the future expansion of multi-functional nano constructs for CC's advanced detection and functional drug delivery.

Inhaled nano-based therapeutics for inflammatory lung diseases: Recent advances and future prospects.

Inflammatory lung diseases related morbidity and mortality impose a significant financial burden. Inflammation is a hallmark of many diseases of the respiratory system which is directly or indirectly linked to adverse health conditions, air pollution, rapid lifestyle changes, and regular outbreaks of microbial infections. The unique anatomical and physiological features of the lungs make them an ideal target organ in the treatment of inflammatory respiratory disease and with the help of inhaled therapy lungs can be targeted directly. The principal objective of this review is to present the comprehensive role of inhaled nano-based therapeutics such as liposomes, niosomes, nanoparticles, nanoemulsion, nanosuspension, and exosomes in the treatment and management of inflammatory respiratory diseases. Inhaled nanomedicines provide targeted diagnosis and treatment, improved drug solubility and distribution, prevent first-pass hepatic metabolism, improved patient compliance, and reduced drug side effects. They overcome several biological barriers in the human body and provide immediate, and quick-onset of action. Future research should be focused on improving the therapeutic efficiency of inhaled nanocarriers and to carry out in-depth mechanistic studies to translate current scientific knowledge for the efficient management of inflammatory lung diseases with minimal or no toxicity.

First-in-Class Phosphorus Dendritic Framework, a Wide Surface Functional Group Palette Bringing Noteworthy Anti-Cancer and Anti-Tuberculosis Activities: What Lessons to Learn?

Based on phenotypic screening, the major advantages of phosphorus dendrimers and dendrons as drugs allowed the discovery of new therapeutic applications, for instance, as anti-cancer and anti-tuberculosis agents. These biological activities depend on the nature of the chemical groups (neutral or cationic) on their surface as well as their generation. As lessons to learn, in the oncology domain, the increase in the generation of metallo-dendrimers is in the same direction as the anti-proliferative activities, in contrast to the development of polycationic dendrimers, where the most potent anti-tuberculosis phosphorus dendrimer was observed to have the lowest generation (G0). The examples presented in this original analysis of phosphorus dendrimers and dendrons provide support for the lessons learned and for the development of new nanoparticles in nanomedicine.

Advances in Nanodelivery of Green Tea Catechins to Enhance the Anticancer Activity.

Cancer is one of the leading causes of death globally. A variety of phenolic compounds display preventative and therapeutic effects against cancers. Green teas are rich in phenolics. Catechins are the most dominant phenolic component in green teas. Studies have shown that catechins have anticancer activity in various cancer models. The anticancer activity of catechins, however, may be compromised due to their low oral bioavailability. Nanodelivery emerges as a promising way to improve the oral bioavailability and anticancer activity of catechins. Research in this area has been actively conducted in recent decades. This review provides the molecular mechanisms of the anticancer effects of catechins, the factors that limit the oral bioavailability of catechins, and the latest advances of delivering catechins using nanodelivery systems through different routes to enhance their anticancer activity.

General sites of nanoparticle biodistribution as a novel opportunity for nanomedicine.

The development of nanomedical devices has led to a considerable number of clinically applied nanotherapeutics. Yet, the overall poor translation of nanoparticular concepts into marketable systems has not met the initial expectations and led to increasing criticism in recent years. Most novel nano approaches thereby use highly refined formulations including a plethora of active targeting sequences, but ultimately fail to reach their target due to a generally high off-target deposition in organs such as the liver or kidney. In this context, we argue that initial nanoparticle (NP) development should not entirely become set on conventional formulation aspects. In contrast, we propose a change of focus towards a prior analysis of general sites of NP in vivo deposition and an assessment of how accumulation in these organs or tissues can be harnessed to develop therapies for site-related pathologies. We therefore give a comprehensive overview of existing nanotherapeutic targeting strategies for specific cell types within three of the usual suspects, i.e. the liver, kidney and the vascular system. We discuss the physiological surroundings and relevant pathologies of described tissues as well as the implications for NP-mediated drug delivery. Additionally, successful cell-selective NP concepts using active targeting strategies are assessed. By bringing together both (patho)physiological aspects and concepts for cell-selective NP formulations, we hope to show a novel opportunity for the development of more promising nanotherapeutic devices.

Nanodiagnostics: A review of the medical capabilities of nanopores.

Modern diagnostics strive to be accurate, fast, and inexpensive in addition to properly identifying the presence of a disease, infection, or illness. Early diagnosis is key; catching a disease in its early stages can be the difference between fatality and treatment. The challenge with many diseases is that detectability of the disease scales with disease progression. Since single molecule sensors, e.g., nanopores, can sense biomolecules at low concentrations, they have the potential to become clinically relevant in many of today's medical settings. With nanopore-based sensing, lower volumes and concentrations are required for detection, enabling it to be clinically beneficial. Other advantages to using nanopores include that they are tunable to an enormous variety of molecules and boast low costs, and fabrication is scalable for manufacturing. We discuss previous reports and the potential for incorporating nanopores into the medical field for early diagnostics, therapeutic monitoring, and identifying relapse/recurrence.

Antitumor Activity and Potential Mechanism of Novel Fullerene Derivative Nanoparticles.

The development of novel nanoparticles as a new generation therapeutic drug platform is an active field of chemistry and cancer research. In recent years, fullerene nanoparticles have received extensive attention due to their unique physical and chemical properties. Properly modified fullerene nanoparticles have excellent biocompatibility and significant anti-tumor activity, which makes them have broad application prospects in the field of cancer therapy. Therefore, understanding the anti-tumor mechanism of fullerene nanoparticles is of great significance for the design and development of anti-tumor drugs with low toxicity and high targeting. This review has focused on various anti-tumor mechanisms of fullerene derivatives and discusses their toxicity and their distribution in organisms. Finally, the review points out some urgent problems that need solution before fullerene derivatives as a new generation of anti-tumor nano-drug platform enter clinical research.

Nanoceutical Adjuvants as Wound Healing Material: Precepts and Prospects.

Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material-cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. This review article provides an update on the various remedies with confirmed wound healing activities of metal-based nanoceutical adjuvanted agents and also other nano-based counterparts from previous experiments conducted by various researchers.

Recent progress in nanomedicine for enhanced cancer chemotherapy.

As one of the most important cancer treatment strategies, conventional chemotherapy has substantial side effects and leads easily to cancer treatment failure. Therefore, exploring and developing more efficient methods to enhance cancer chemotherapy is an urgently important problem that must be solved. With the development of nanotechnology, nanomedicine has showed a good application prospect in improving cancer chemotherapy. In this review, we aim to present a discussion on the significant research progress in nanomedicine for enhanced cancer chemotherapy. First, increased enrichment of drugs in tumor tissues relying on different targeting ligands and promoting tissue penetration are summarized. Second, specific subcellular organelle-targeted chemotherapy is discussed. Next, different combinational strategies to reverse multidrug resistance (MDR) and improve the effective intracellular concentration of therapeutics are discussed. Furthermore, the advantages of combination therapy for cancer treatment are emphasized. Finally, we discuss the major problems facing therapeutic nanomedicine for cancer chemotherapy, and propose possible future directions in this field.

Recent advances in prodrug-based nanoparticle therapeutics.

Extensive research into prodrug modification of active pharmaceutical ingredients and nanoparticle drug delivery systems has led to unprecedented levels of control over the pharmacological properties of drugs and resulted in the approval of many prodrug or nanoparticle-based therapies. In recent years, the combination of these two strategies into prodrug-based nanoparticle drug delivery systems (PNDDS) has been explored as a way to further advance nanomedicine and identify novel therapies for difficult-to-treat indications. Many of the PNDDS currently in the clinical development pipeline are expected to enter the market in the coming years, making the rapidly evolving field of PNDDS highly relevant to pharmaceutical scientists. This review paper is intended to introduce PNDDS to the novice reader while also updating those working in the field with a comprehensive summary of recent efforts. To that end, first, an overview of FDA-approved prodrugs is provided to familiarize the reader with their advantages over traditional small molecule drugs and to describe the chemistries that can be used to create them. Because this article is part of a themed issue on nanoparticles, only a brief introduction to nanoparticle-based drug delivery systems is provided summarizing their successful application and unfulfilled opportunities. Finally, the review's centerpiece is a detailed discussion of rationally designed PNDDS formulations in development that successfully leverage the strengths of prodrug and nanoparticle approaches to yield highly effective therapeutic options for the treatment of many diseases.

Functionalized Reduced Graphene Oxide as a Versatile Tool for Cancer Therapy.

Cancer is one of the deadliest diseases in human history with extremely poor prognosis. Although many traditional therapeutic modalities-such as surgery, chemotherapy, and radiation therapy-have proved to be successful in inhibiting the growth of tumor cells, their side effects may vastly limited the actual benefits and patient acceptance. In this context, a nanomedicine approach for cancer therapy using functionalized nanomaterial has been gaining ground recently. Considering the ability to carry various anticancer drugs and to act as a photothermal agent, the use of carbon-based nanomaterials for cancer therapy has advanced rapidly. Within those nanomaterials, reduced graphene oxide (rGO), a graphene family 2D carbon nanomaterial, emerged as a good candidate for cancer photothermal therapy due to its excellent photothermal conversion in the near infrared range, large specific surface area for drug loading, as well as functional groups for functionalization with molecules such as photosensitizers, siRNA, ligands, etc. By unique design, multifunctional nanosystems could be designed based on rGO, which are endowed with promising temperature/pH-dependent drug/gene delivery abilities for multimodal cancer therapy. This could be further augmented by additional advantages offered by functionalized rGO, such as high biocompatibility, targeted delivery, and enhanced photothermal effects. Herewith, we first provide an overview of the most effective reducing agents for rGO synthesis via chemical reduction. This was followed by in-depth review of application of functionalized rGO in different cancer treatment modalities such as chemotherapy, photothermal therapy and/or photodynamic therapy, gene therapy, chemotherapy/phototherapy, and photothermal/immunotherapy.

Drug Resistance in Metastatic Breast Cancer: Tumor Targeted Nanomedicine to the Rescue.

Breast cancer, specifically metastatic breast, is a leading cause of morbidity and mortality in women. This is mainly due to relapse and reoccurrence of tumor. The primary reason for cancer relapse is the development of multidrug resistance (MDR) hampering the treatment and prognosis. MDR can occur due to a multitude of molecular events, including increased expression of efflux transporters such as P-gp, BCRP, or MRP1; epithelial to mesenchymal transition; and resistance development in breast cancer stem cells. Excessive dose dumping in chemotherapy can cause intrinsic anti-cancer MDR to appear prior to chemotherapy and after the treatment. Hence, novel targeted nanomedicines encapsulating chemotherapeutics and gene therapy products may assist to overcome cancer drug resistance. Targeted nanomedicines offer innovative strategies to overcome the limitations of conventional chemotherapy while permitting enhanced selectivity to cancer cells. Targeted nanotheranostics permit targeted drug release, precise breast cancer diagnosis, and importantly, the ability to overcome MDR. The article discusses various nanomedicines designed to selectively target breast cancer, triple negative breast cancer, and breast cancer stem cells. In addition, the review discusses recent approaches, including combination nanoparticles (NPs), theranostic NPs, and stimuli sensitive or "smart" NPs. Recent innovations in microRNA NPs and personalized medicine NPs are also discussed. Future perspective research for complex targeted and multi-stage responsive nanomedicines for metastatic breast cancer is discussed.

Research progress and application opportunities of nanoparticle-protein corona complexes.

Nanoparticles (NPs) can be used to design for nanomedicines with different chemical surface properties owing to their size advantages and the capacity of specific delivery to targeted sites in organisms. The discovery of the presence of protein corona (PC) has changed our classical view of NPs, stimulating researchers to investigate the in vivo fate of NPs as they enter biological systems. Both NPs and PC have their specificity but complement each other, so they should be considered as a whole. The formation and characterization of NP-PC complexes provide new insights into the design, functionalization, and application of nanocarriers. Based on progress of recent researches, we reviewed the formation, characterization, and composition of the PC, and introduced those critical factors influencing PC, simultaneously expound the effect of PC on the biological function of NPs. Especially we put forward the opportunities and challenges when NP-PC as a novel nano-drug carrier for targeted applications. Furthermore, we discussed the pros versus cons of the PC, as well as how to make better PC in the future application of NPs.

Application of nanotechnology in drug delivery systems for respiratory diseases (Review).

Respiratory disease is a common disease with a high incidence worldwide, which is a serious threat to human health, and is considered a societal and economic burden. The application of nanotechnology in drug delivery systems has created new treatments for respiratory diseases. Within this context, the present review systematically introduced the physicochemical properties of nanoparticles (NPs); reviewed the current research status of different nanocarriers in the treatment of respiratory diseases, including liposomes, solid lipid nanocarriers, polymeric nanocarriers, dendrimers, inorganic nanocarriers and protein nanocarriers; and discussed the main advantages and limitations of therapeutic nanomedicine in this field. The application of nanotechnology overcomes drug inherent deficiencies to a certain extent, and provides unlimited potential for the development of drugs to treat respiratory diseases. However, most of the related research work is in the preclinical experimental stage and safety assessment is still a challenging task. Future studies are needed to focus on the performance modification, molecular mechanism and potential toxicity of therapeutic nanomedicine.

Key principles and methods for studying the endocytosis of biological and nanoparticle therapeutics.

Endocytosis is a critical step in the process by which many therapeutic nanomedicines reach their intracellular targets. Our understanding of cellular uptake mechanisms has developed substantially in the past five years. However, these advances in cell biology have not fully translated to the nanoscience and therapeutics literature. Misconceptions surrounding the role of different endocytic pathways and how to study these pathways are hindering progress in developing improved nanoparticle therapies. Here, we summarize the latest insights into cellular uptake mechanisms and pathways. We highlight limitations of current systems to study endocytosis, particularly problems with non-specific inhibitors. We also summarize alternative genetic approaches to robustly probe these pathways and discuss the need to understand how cells endocytose particles in vivo. We hope that this critical assessment of the current methods used in studying nanoparticle uptake will guide future studies at the interface of cell biology and nanomedicine.