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Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the blood‒brain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.

Despite continual progress in the technologies and regimens for cancer therapy, the treatment outcome of fatal metastatic breast cancer is far from satisfactory. Encouragingly, nanotechnology has emerged as a valuable tool to optimize drug delivery process in cancer therapy via preventing the cargos from degradation, improving the tumor-targeting efficiency, enhancing therapeutic agents’ retention in specific sites, and controlling drug release. In the last decade, several mechanisms of suppressing tumor metastasis by functional nano drug delivery systems (NDDSs) have been revealed and a guidance for the rational design of anti-metastasis NDDSs is summarized, which consist of three aspects: optimization of physiochemical properties, tumor microenvironment remodeling, and biomimetic strategies. A series of medicinal functional biomaterials and anti-metastatic breast cancer NDDSs constructed by our team are introduced in this review. It is hoped that better anti-metastasis strategies can be inspired and applied in clinic.

Central Nervous System (CNS) disorders are one of the major causes of fatalities in the world today. Thus, it is essential to transport a considerable amount of drugs to a specific brain location f...

Today the nano drug delivery systems are among the hot topics in drug design and pharmacy studies. Extensive researches are conducted worldwide for obtaining more effective therapeutics and screen the best drug carrier

In recent years, nanotechnology has been widely used in modern biomedicine. Nano-delivered drugs have great advantages that other platforms do not have in terms of human drug energy release, in viv...

Nano drug delivery systems can provide the opportunity to reduce side effects and improve the therapeutic aspect of a variety of drugs. Bortezomib (BTZ) is a proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma. Severe side effects of BTZ are the major dose-limiting factor. Particulate drug delivery systems for BTZ are polymeric and lipidic drug delivery systems. This review focussed on lipidic-nano drug delivery systems (LNDDSs) for the delivery of BTZ.LNDDSs including liposomes, solid lipid nanoparticles, and self-nanoemulsifying drug delivery systems showed reduce systemic side effects, improved therapeutic efficacy, and increased intestinal absorption. Besides LNDDSs were used to target-delivery of BTZ to cancer.Overall, LNDDSs can be considered as a novel delivery system for BTZ to resolve the treatment-associated restrictions.

The surface-modified paclitaxel nanoparticles were prepared to observe its inhibitory effect on the intimal and mediator proliferation and the improvement of vascular remodeling after rabbit abdominal aortic injury. First, paclitaxel nanoparticles were prepared by ultrasonic emulsification solvent evaporation method. The surface of paclitaxel nanoparticles was modified by physical adsorption, the nanoparticles were characterized and the encapsulation efficiency was evaluated. Secondly, the endometrial thickness was measured by hematoxylin and eosin staining, and a spheroid with a smooth surface was observed under a scanning electron microscope. Finally, compared with the control group, local infusion of paclitaxel nanoparticles could effectively inhibit the proliferation of vascular endothelium in a dose-dependent manner. Local intravascular infusion of paclitaxel nanoparticle suspension can effectively inhibit the proliferation of vascular endothelial cells, and its inhibitory effect increases with the increase of the concentration of nanoparticle suspension. The paclitaxel nanoparticle suspension at a concentration of 30 mg/ml can play a good inhibitory role.

Cancer has been considered as the most cause of death in world. Employing of nanocarriers as drug delivery systems provide a platform for delivering drugs with increasing the anti-cancer efficacy, enhancing bioavailability of drugs, reducing side effects, enhancing the circulation half-life of drugs, improving the distribution of drugs and overcoming drug resistance. A number of nanocarriers have been studied as drug delivery systems for improving the treatment of cancer including liposomes, micelle, polymeric nanoparticles, carbon nanotubes, dendrimers, solid lipid nanoparticle (SLN) and nanostructure lipid carrier (NLC). In order to enhance recognition and internalization of nanocarriers by the target tissues, their surfaces can be modified with targeting ligands such as integrins, transferrin, folic acid, polysaccharides and antibodies. In this chapter, we are going to introduce the targeted nanocarriers for improving the cytotoxic action of drugs with further attempt of decreasing dose to achieve higher anticancer activity. Targeted nanocarriers would provide a promising therapeutic approach for cancer.

Over recent years, advancements in nanomedicine have allowed new approaches to diagnose and treat tumors. Nano drug delivery systems exploit the enhanced permeability and retention (EPR) effect and enter the tumor tissue's interstitial space. However, tumor barriers play a crucial role, and cause inefficient EPR or the homing effect. Mounting evidence supports the hypothesis that the components of the tumor microenvironment, such as the extracellular matrix, and cellular and physiological components collectively or cooperatively hinder entry and distribution of drugs, and therefore, limit the theragnostic applications of cancer nanomedicine. This abnormal tumor microenvironment plays a pivotal role in cancer nanomedicine and was recently recognized as a promising target for improving nano-drug delivery and their therapeutic outcomes. Strategies like passive or active targeting, stimuli-triggered nanocarriers, and the modulation of immune components have shown promising results in achieving anticancer efficacy. The present review focuses on the tumor microenvironment and nanoparticle-based strategies (polymeric, inorganic and organic nanoparticles) for intruding the tumor barrier and improving therapeutic effects.

Nanotechnology has recently become popular due to its potential for biomedical applications, especially for cancer treatment. Nanotechnology, featuring responsiveness to stimuli and stable drug release, has been widely used for the delivery of chemotherapeutic drugs, which are commonly used in the treatment of osteosarcoma. Smart stimuli-responsive nanotechnology is expected to improve the treatment of osteosarcoma. Herein, we focus on the latest research on nanomaterials in treating osteosarcoma that respond to internal and external stimuli. We also discuss nanocarriers with targeting ligands and the use of smart nanotechnology to partially reverse the multidrug resistance of osteosarcoma.

Nanotechnology is the science of material featuring between 10?9 and 10?7 of a meter. Pharmaceutical nanotechnology is the latest advancement in pharmacology known for presenting multiple newer tools, opportunities and scope in drug delivery system having signi?cant applications in disease diagnostics and treatment. Nano drug delivery system comprised of nano-sized products which can be transformed in numerous ways to improve their characteristics by leading to prolonged circulation, improved drug localization and enhanced drug ef?cacy. The aim of this paper is to summarize the types of pharma nano-systems and nanoparticles commonly used in drug delivery system along with their advantages, disadvantages and health issues related to nano drug delivery. Keywords: Nanotechnology, Nano Drug Delivery, Nanoparticles, Liposomes.

In view of the worldwide serious health threat of type 2 diabetes mellitus (T2DM), natural sources of chemotherapies have been corroborated as the promising alternatives, with the excellent antidiabetic activities, bio-safety, and more cost-effective properties. However, their clinical application is somewhat limited, because of the poor solubility, instability in the gastrointestinal tract (GIT), low bioavailability, and so on. Nowadays, to develop nanoscaled systems has become a prominent strategy to improve the drug delivery of phytochemicals. In this review, we primarily summarized the intervention mechanisms of phytocompounds against T2DM and presented the recent advances in various nanosystems of antidiabetic phytocompounds. Selected nanosystems were grouped depending on their classification and structures, including polymeric NPs, lipid-based nanosystems, vesicular systems, inorganic nanocarriers, and so on. Based on this review, the state-of-the-art nanosystems for phytocompounds in T2DM treatment have been presented, suggesting the preponderance and potential of nanotechnologies.

Gastric cancer (GC) is a life-threatening malignant tumor present in the digestive tract. In this study the connection of miR-199a-3p, which is a gene abnormally expressed in GC, was analyzed along with the pathological parameters as well as the prognosis of GC patients. Moreover, the influence of miR-199a-3p inhibitor delivered through the nano-drug delivery system (NDDS) was studied in regard of GC cell survival and metastasis, seeking to reveal its potential treatment effect. During the conduction of the study, high miR-199a-3p expression was detected in GC tissues, sera, and cells along with its value for GC screening and pathological progression. In molecular research, polylactic-glycolic acid (PLGA) nanoparticles (NPs)-miRNA complexes that shaped like symmetrical spheres under the scanning electron microscope (SEM) were prepared to increase or decrease the levels of miR-199a-3p. The GC cell survival and metastasis was remarkably facilitated by the elevated miR-199a-3p, and its knockdown produced an opposite effect to markedly inhibit GC cell survival and metastasis. In conclusion, the expression in GC patients was increased by miR-199a-3p and the ability of its inhibitor delivered through the NDDS was demonstrated to control the survival and metastasis of GC cells.

Upper gastrointestinal (GI) carcinomas are characterized as one of the deadliest cancer types with the highest recurrence rates. Their treatment is challenging due to late diagnosis, early metastasis formation, resistance to systemic therapy and complicated surgeries performed in poorly accessible locations. Current cancer medication face deficiencies such as high toxicity and systemic side-effects due to the non-specific distribution of the drug agent. Nanomedicine has the potential to offer sophisticated therapeutic possibilities through adjusted delivery systems. This review aims to provide an overview of novel approaches and perspectives on nanoparticle (NP) drug delivery systems for gastrointestinal carcinomas. Present regimen for the treatment of upper GI carcinomas are described prior to detailing various NP drug delivery formulations and their current and potential role in GI cancer theranostics with a specific emphasis on targeted nanodelivery systems. To date, only a handful of NP systems have met the standard of care requirements for GI carcinoma patients. However, an increasing number of studies provide evidence supporting NP-based diagnostic and therapeutic tools. Future development and strategic use of NP-based drug formulations will be a hallmark in the treatment of various cancers. This article seeks to highlight the exciting potential of novel NPs for targeted cancer therapy in GI carcinomas and thus provide motivation for further research in this field.

Vitiligo is a depigmentation disease that seriously affects the physical health, mental health and quality of life of a patient. Therapeutic aim at control immunoreaction by relieving oxidative stress. Unfortunately, the cuticle barrier function and lack of specific accumulation lead to unsatisfactory therapeutic outcomes and side effects. The introduction and innovation of nanotechnology offers inspiration and clues for the development of new strategies to treat vitiligo. However, not many studies have been done to interrogate how nanotechnology can be used for vitiligo treatment. In this review, we summarize and analyze recent studies involving nano-drug delivery systems for the treatment of vitiligo, with a special emphasis on liposomes, niosomes, nanohydrogel and nanoparticles. These studies made significant progress by either increasing drug loading efficiency or enhancing penetration. Based on these studies, there are three proposed principles for topical nano-drug delivery systems treatment of vitiligo including the promotion of transdermal penetration, enhancement of drug retention and facilitation of melanin regeneration. The presentation of these ideas may provide inspirations for the future development of topical drug delivery systems that will conquer vitiligo.

Ursolic acid (UA), a natural pentacyclic triterpenoid, possesses widespread biological and pharmacological activities. However, drawbacks such as low bioavailability, poor targeting and rapid metabolism greatly hinder its further clinical application. Recently, with the development of nanotechnology, various UA nanosystems have emerged as promising strategies for effective cancer therapy. This article reviews various types of UA-based nano-delivery systems, primarily with emphasis placed on novel UA-based carrier-free nano-drugs, which are considered to be innovative methods for cancer therapy. Moreover, this review presents carrier-free nano-drugs that co-assembled of UA and photosensitizers that displayed synergistic antitumor performance. Finally, the article also describes the development and challenges of UA nanosystems for future research in this field. Overall, the information presented in this review will provide new insight into the rational utilization of nano-drugs in cancer therapy., Graphical abstract Image, graphical abstract

Background Skin cancers are among the widely prevalent forms of cancer worldwide. The increasing industrialization and accompanied environmental changes have further worsened the skin cancer statistics. The stern topical barrier although difficult to breach is a little compromised in pathologies like skin cancer. The therapeutic management of skin cancers has moved beyond chemotherapy and surgery. Main body of the abstract The quest for a magic bullet still prevails, but topical drug delivery has emerged as a perfect modality for localized self-application with minimal systemic ingress for the management of skin cancers. Advances in topical drug delivery as evidenced by the exploration of nanocarriers and newer technologies like microneedle-assisted/mediated therapeutics have revolutionized the paradigms of topical treatment. The engineered nanovectors have not only been given the liberty to experiment with a wide-array of drug carriers with very distinguishing characteristics but also endowed them with target specificity. The biologicals like nucleic acid-based approaches or skin penetrating peptide vectors are another promising area of skin cancer therapeutics which has demonstrated potential in research studies. In this review, a panoramic view is presented on the etiology, therapeutic options, and emerging drug delivery modalities for skin cancer. Short conclusion Nanocarriers have presented innumerable opportunities for interventions in skin cancer therapeutics. Challenge persists for the bench to bedside translation of these highly potential upcoming therapeutic strategies. Graphic abstract

Graphical abstract In this comment, the opportunities of black phosphorus-based nano-drug delivery systems for cancer treatment are highlighted.Image, graphical abstract

Nano-drug delivery systems (NDDS) for colon-targeted drug delivery are an active area of research on local diseases affecting the colon, such as ulcerative colitis, Crohn's disease, colon cancer, and for the delivery of peptide or protein drugs and vaccinations. In particular, targeted nano-drug delivery to the colon is advantageous for colon-specific diseases because nanoparticles can accumulate in diseased parts, improve the efficacies of therapeutics, and enable localized treatments, which reduces systemic toxicity. However, there are many hurdles, such as burst drug release, enzyme and acidic degradation of drug and carrier in the stomach, pH variations, mucus entrapment, and systemic uptake in the upper small intestine, which could challenge and compromise the successful delivery of NDDS to the colon. With advancements in NDDS, it may be possible to overcome these challenges leading to efficient drug delivery for colon-specific disorders. This review describes a few of the potential colon-specific drug delivery areas and the challenges faced by colon-targeted orally administered delivery systems, and provides an updated summary of recent advances in the development of orally administered NDDS for colon targeting, and the future advances in this research.

Purpose: Maytansine (DM1) is a potent anticancer drug and limited in clinical application due to its poor water solubility and toxic side effects. Zein is widely used in nano drug delivery systems due to its good biocompatibility. In this study, we prepared DM1-loaded zein nanoparticles (ZNPs) to achieve tumor targeting and reduce toxic side effects of DM1. Methods: ZNPs were prepared by phase separation and Box-Behnken design was used to optimize the formulation. Then, confocal fluorescence microscope and flow cytometry were used to determine cellular uptake of ZNPs. A549 cells were cultured in vitro to study cytotoxicity and used to establish tumor xenografts in nude mice. Biodistribution and antitumor activity of ZNPs were performed in vivo experiments. In addition, we also performed histological and immunohistochemical examinations on tumors and viscera. Results: The optimal prescription was obtained by using 120 μL zein added to 2 mL water under stirring in 300 rpm. The encapsulation efficiency and drug loading were 82.97 ± 0.80% and 3.32 ± 0.03%, respectively. We found that DM1-loaded ZNPs have a strong inhibitory effect on A549 cells, which stemmed from the ability of ZNPs to enhance cellular uptake. Furthermore, we demonstrated that DM1-loaded ZNPs exhibits a better antitumor efficacy than DM1, which tumor inhibition rate were 97.3% and 92.7%, respectively. The biodistribution revealed that ZNPs could targeted to tumor. Finally, we confirmed by histological that DM1-loaded ZNPs are nontoxic. Conclusion: DM1-loaded ZNPs have considerable antitumor activity. Thus, DM1-loaded ZNPs are a promising treatment of non-small cell lung cancer.

Skin damages are defined as one of most common lesions people suffer from, some of wounds are notoriously difficult to eradicate such as chronic wounds and deep burns. Existing wound therapies have been proved to be inadequate and far from satisfactory. The cutting-edge nanotechnology offers an unprecedented opportunity to revolutionize and invent new therapies or boost the effectiveness of current medical treatments. In particular, the nano-drug delivery systems anchor bioactive molecules to applied area, sustain the drug release and explicitly enhance the therapeutic efficacies of drugs, thus making a fine figure in field relevant to skin regeneration. This review summarized and discussed the current nano-drug delivery systems holding pivotal potential for wound healing and skin regeneration, with a special emphasis on liposomes, polymeric nanoparticles, inorganic nanoparticles, lipid nanoparticles, nanofibrous structures and nanohydrogel.

Although many solid tumors use the lymphatic system to metastasize, there are few treatment options that directly target cancer present in the lymphatic system, and those that do are highly invasive, uncomfortable, and/or have limitations. In this review we provide a brief overview of lymphatic function and anatomy, discusses changes that befall the lymphatics in cancer and the mechanisms by which these changes occur, and highlight limitations of lymphatic drug delivery. We then go on to summarize relevant techniques and new research for targeting cancer populations in the lymphatics and enhancing drug delivery intralymphatically, including intralymphatic injections, isolated limb perfusion, passive nano drug delivery systems, and actively targeted nanomedicine.

Conventional drug delivery systems are inadequate in providing essential cyto-architecture restoration and connection patterns because of restrictions posed by the restrictive blood-brain barrier. Nanotechnological approaches involve various nano-sized carrier systems and other devices, which stimulate the action of therapeutic agents on molecular level and revolutionized the treatment and diagnosis of neurodegenerative disorders with minimal side effects. Over the conventional approaches, nanotechnological approaches have various promising strategies to cross blood brain barrier and increase the bioavailability of therapeutics in brain. This review article emphasizes the current and future utility of nano drug delivery systems for the treatment of various neurodegenerative disorders.

The blood–brain barrier (BBB) plays a vital role in the protection and maintenance of homeostasis in the brain. In this way, it is an interesting target as an interface for various types of drug delivery, specifically in the context of the treatment of several neuropathological conditions where the therapeutic agents cannot cross the BBB. Drug toxicity and on-target specificity are among some of the limitations associated with current neurotherapeutics. In recent years, advances in nanodrug delivery have enabled the carrier system containing the active therapeutic drug to target the signaling pathways and pathophysiology that are closely linked to central nervous system (CNS) disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), multiple sclerosis (MS), brain tumor, epilepsy, ischemic stroke, and neurodegeneration. At present, among the nano formulations, solid lipid nanoparticles (SLNs) have emerged as a putative drug carrier system that can deliver the active therapeutics (drug-loaded SLNs) across the BBB at the target site of the brain, offering a novel approach with controlled drug delivery, longer circulation time, target specificity, and higher efficacy, and more importantly, reducing toxicity in a biomimetic way. This paper highlights the synthesis and application of SLNs as a novel nontoxic formulation strategy to carry CNS drugs across the BBB to improve the use of therapeutics agents in treating major neurological disorders in future clinics.

Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide and its incidence is increasing due to the ageing population. Currently, the main limitations of AD treatment are low blood-brain barrier permeability, severe off-target of drugs, and immune abnormality. In this review, four hypotheses for Alzheimer's pathogenesis and three challenges for Alzheimer's drug delivery are discussed. In addition, this article summarises the different strategies of brain targeting nano-drug delivery systems (NDDSs) developed in the last 10 years. These strategies include receptor-mediated (transferrin receptor, low-density lipoprotein receptor-related protein, lactoferrin receptor, etc.), adsorption-mediated (cationic, alkaline polypeptide, cell-penetrating peptides, etc.), and transporter-mediated (P-gp, GLUT1, etc.). Moreover, it provides insights into novel strategies used in AD, such as exosomes, virus-like particles, and cell membrane coating particles. Hence, this review will help researchers to understand the current progress in the field of NDDSs for the central nervous system and find new directions for AD therapy.HighlightsCharacteristics and challenges based on the pathogenesis of AD were discussed.Recent advances in novel brain-targeting NDDSs for AD over the past 10 years were summarised.

The abnormal structure and function of blood vessels in the TME are obvious characteristics of the tumour. Abnormal blood vessels with high leakage support the occurrence of malignant tumours and increase the possibility of tumour cell invasion and metastasis. The formation of abnormal vascular also enhances immunosuppression and prevents the delivery of chemotherapy drugs to deeper tumours. Therefore, the normalisation of tumour blood vessels is a very promising approach to improve anti-tumour efficacy, aiming to restore the structural integrity of vessels and improve drug delivery efficiency and anti-tumour immunity. In this review, we have summarised strategies to improve cancer treatment that via nano drug delivery technology regulates the normalisation of tumour blood vessels. The treatment strategies related to the structure and function of tumour blood vessels such as angiogenesis factors, tumour-associated macrophages, tumour vascular endothelial cells, tumour-associated fibroblasts and immune checkpoints in the TME were mainly discussed. The normalisation of tumour blood vessels presents new opportunities and challenges for the more efficient delivery of nanoparticles to tumour tissues and cells and an innovative combination of treatments for cancer.

Nanoliposomes are one of the leading potential nano drug delivery systems capable of targeting chemotherapeutics to tumor sites because of their passive nano-targeting capability through the enhanced permeability and retention (EPR) effect for cancer patients. Recent advances in nano-delivery systems have inspired the development of a wide range of nanotargeted materials and strategies for applications in preclinical and clinical usage in the cancer field. Nanotargeted 188Re-liposome is a unique internal passive radiotheranostic agent for nuclear imaging and radiotherapeutic applications in various types of cancer. This article reviews and summarizes our multi-institute, multidiscipline, and multi-functional studied results and achievements in the research and development of nanotargeted 188Re-liposome from preclinical cells and animal models to translational clinical investigations, including radionuclide nanoliposome formulation, targeted nuclear imaging, biodistribution, pharmacokinetics, radiation dosimetry, radiation tumor killing effects in animal models, nanotargeted radionuclide and radio/chemo-combination therapeutic effects, and acute toxicity in various tumor animal models. The systemic preclinical and clinical studied results suggest 188Re-liposome is feasible and promising for in vivo passive nanotargeted radionuclide theranostics in future cancer care applications.

Funding: this work was supported by a grant from NMRC-CIRG to CTY. APK was supported by grants from National Medical Research Council of Singapore, NCIS Yong Siew Yoon Research Grant through donations from the Yong Loo Lin Trust and by the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centers of Excellence initiative to Cancer Science Institute of Singapore, National University of Singapore. R.M. acknowledges financial supports of Kerman University of Medical Sciences. Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed

The nano drug delivery system has already entered into the market for commercialization and so it is dynamically studied for the administration of a variety of drugs for oral applications. The nanocarriers have been proven to have significant contribution in improving therapeutic outcomes and hence novel carriers such as nanovesicles and nanoporous approaches have been established for ocular transport. This chapter outlines basic anatomy and notifies with facts about various delivery means that target distinctive therapeutic spots. The chapter also discusses different obstacles for drug transport and the application of nanocarriers for prolonged retention and improvement in drug targeting. In conclusion, the existing limitations that restrict the quick development of nanotechnology in the ocular field are explained with a prominence on toxicity as well as commercialization of recognized nanocarriers.

Many bioactive natural products are derived from traditional Chinese medicine. Some of them showed good treatment potential in tumor chemotherapy. However, limited by the poorly solubility and non-selective toxicity of most of bioactive natural products, their antitumor efficacy could not be further applied in clinicals. Nano-drug delivery systems provided good platforms for bioactive natural products in antitumor treatment, and many tumor microenvironment-responsive nano-delivery carriers facilitated them to achieve more accurate tumor targeting and less toxicity, and finally improved antitumor ability of bioactive natural products.

Alzheimer's disease (AD) is a neurodegenerative disorder in which the death of brain cells causes memory loss and cognitive decline. Existing drugs only suppress symptoms or delay further deterioration but do not address the cause of the disease. In spite of screening numerous drug candidates against various molecular targets of AD, only a few candidates, such as acetylcholinesterase inhibitors, are currently utilized as an effective clinical therapy. Currently, nano-based therapies can make a difference, providing new therapeutic options by helping drugs to cross the blood-brain barrier and enter the brain more effectively. The main aim of this review was to highlight advances in research on the development of nano-based therapeutics for improved treatment of AD.

Cancer therapy is an attractive research field in basic and clinical studies. Among them, nano-based antitumor drugs and delivery systems play increasingly crucial role in tumor treatment, while they are still faced with complicated surrounding environments. Therefore, this review summarized the tumor micro-environments and some nano-based delivery systems including some FDA-approved nano-drugs for clinical use, in addition, the tumor microenvironment sensitive drug delivery systems are also illustrated.

Around 200 cytokines with roles in cell signaling have been identified and studied, with the vast majority belonging to the four-α-helix bundle family. These proteins exert their function by binding to specific receptors and are implicated in many diseases. The use of several cytokines as therapeutic targets has been approved by the FDA, however their rapid clearance in vivo still greatly limits their efficacy. Nano-based drug delivery systems have been widely applied in nanomedicine to develop safe, specific and controlled delivery techniques. Nevertheless, each nanomaterial has its own specifications and their suitability towards the biochemical and biophysical properties of the selected drug needs to be determined, weighing in the final choice of the ideal nano drug delivery system. Nanoparticles remain the most used vehicle for cytokine delivery, where polymeric carriers represent the vast majority of the studied systems. Liposomes and gold or silica nanoparticles are also explored and discussed in this review. Additionally, surface functionalization is of great importance to facilitate the attachment of a wide variety of molecules and modify features such as bioavailability. Since the monitoring of cytokine levels has an important role in early clinical diagnosis and for assessing therapeutic efficacy, nanotechnological advances are also valuable for nanosensor development., This work was supported by the “Contrato-Programa” UIDB/04050/2020 funded by national funds through the FCT I.P. and project FUN2CYT: Harnessing the potential for biomedical applications of pleiotropic cytokines LIF and oncostatin M (POCI-01-0145-FEDER-030568) supported by Programa Operacional Competitividade e Internacionalização (FEDER) and FCT, IP. Anabela Gonçalves acknowledges her PhD scholarship from FCT (SFRH/BD/146807/2019).

Despite the commendable milestones achieved in molecular maxillofacial pathology in the last decade, there remains a paucity of utilization of ancillary nanomolecular tools that complement the omics-based approaches. As the advent of omics science transforms our understanding of tumour biology from a phenomenological to a complex network (systems-oriented) paradigm, several ancillary tools have emerged to improve the scope of individualized medicine. Targeted nano drug delivery systems have significantly reduced toxicity of chemotherapeutic agents in a precise manner. Many conventional cancer therapies are limited in efficacy and this has led to the emergence of nanomedical innovations. Despite the success of nanomedicine, a major challenge that persists is tumour heterogeneity and biological complexity. A good understanding of the interaction between inorganic nanoparticles and the biological systems has led to the development of better tools for individualized medicine. Tools such as the composite organic-inorganic nanoparticles (COINs) and the quantum dots (QD) have significantly improved the identification and quantification of disease biomarkers, histopathological detection methods, as well as improving the clinical translation and utility of these nanomaterials. Nanomedicine has lent credence to several multipronged theranostic applications in medicine, and this has improved the medical practice tremendously. Despite the palpable influence of nanomedicine on the delivery of individualized medical therapies, the term “nanodentistry” remains in the background without much hype, albeit some progress has been made in this area. Hence, this review discusses the potential and challenges of nanodentistry in the diagnosis and treatment of maxillofacial pathologies, particularly cancer in resource-limited settings., Materials science; Dentistry; Biomedical engineering; Cancer; Nanodentistry; Precision dentistry; Maxillofacial pathology; Africa.

In this study, 5-fluorouracil (5-FU) is delivered to target colon without the interference of mononuclear phagocyte system (MPS).Outer membrane vesicles (OMVs) were used as the biological shield to disguise mesoporous silica (MSN) and 5-FU. OMVs-MSN-5-FU were prepared by high pressure co-extrusion, and characterised on the basis of size, drug loading, transmission electron microscope, infra-red spectroscopy, differential scanning calorimetry, thermal gravity analysis, %OMVs-MSN-5-FU with -18.22 ± 0.17 mV zeta potential and 90.4 ± 9.1 nm size were used for oral treatment of colon cancer. Drug loading of the drug was 50.22%±0.17 (w/w). The cumulative release of OMVs-MSN-5-FU reached 75.07%±0.94 in tumour microenvironment. The percentage of cell viability of OMVs-MSN-5-FU was 33.75%±2.73.The study provided a promising nano platform for the targeting treatment of colon cancer.

Nanostructured surfaces feature promising biological properties on biomaterials attracting large interest at basic research, implant industry development, and bioengineering applications. Thou, nanoscale interactions at a molecular and cellular level are not yet completely understood and its biological and clinical implications need to be further elucidated. As follows, the aim of this comprehensive review was to evaluate nanostructured surfaces at biomedical implants focusing on surface development, nanostructuration, and nanoengineered drug delivery systems that can induce specific cell interactions in all relevant aspects of biological, reparative, anti-bacterial, anti-inflammatory and clinical processes. The methods and the physio-chemical properties involved in nanotopography performance, the main cellular characteristics involved at surface/cell interaction, and a summary of results and outlooks reported in studies applying nanostructured surfaces and nano-drug delivery systems is presented. The future prospects and commercial translation of this developing field, particularly concerning multifunctional nanostructured surfaces and its clinical implications are further discussed. At a cellular level, nanostructured biomedical implant surfaces can enhance osteogenesis by targeting osteoblasts, osteocytes, and mesenchymal cells, stimulate fibroblast/epithelial cells proliferation and adherence, inhibit bacterial cell proliferation and biofilm accumulation, and act as immune-modulating surfaces targeting macrophages and reducing pro-inflammatory cytokine expression. Moreover, several methodological options to create drug-delivery systems on metallic implant surfaces are available, however, the clinical translation is yet incomplete. The efficiency of which nanostructured/nano-delivery surfaces may target specific cell interactions and favor clinical outcomes needs to be further elucidated in pre-clinical and clinical studies, along with engineering solutions for commercial translation and approval of controlling agencies.

In order to enhance the targeting efficiency and reduce anti-tumor drug’s side effects, topotecan (TPT) and F7 were co-loaded in thermosensitive liposomes (F7-TPT-TSL), which show enhanced permeability and retention in tumors, as well as local controlled release by heating in vitro. TPT is a water-soluble inhibitor of topoisomerase I that is converted to an inactive carboxylate structure under physiological conditions (pH 7.4). F7 is a novel drug significantly resistant to cyclin-dependent kinase but its use was restricted by its high toxicity. F7-TPT-TSL had excellent particle distribution (about 103 nm), high entrapment efficiency (>95%), obvious thermosensitive property, and good stability. Confocal microscopy demonstrated specific higher accumulation of TSL in tumor cells. MTT proved F7-TPT-TSL/H had strongest cell lethality compared with other formulations. Then therapeutic efficacy revealed synergism of TPT and F7 co-loaded in TSL, together with hyperthermia. Therefore, the F7-TPT-TSL may serve as a promising system for temperature triggered cancer treatment.

Advances in nanomedicine, including early cancer detection, targeted drug delivery, and personalized approaches to cancer treatment are on the rise. For example, targeted drug delivery systems can improve intracellular delivery because of their multifunctionality. Novel endogenous-based and exogenous-based stimulus-responsive drug delivery systems have been proposed to prevent the cancer progression with proper drug delivery. To control effective dose loading and sustained release, targeted permeability and individual variability can now be described in more-complex ways, such as by combining internal and external stimuli. Despite these advances in release control, certain challenges remain and are identified in this research, which emphasizes the control of drug release and applications of nanoparticle-based drug delivery systems. Using a multiscale and multidisciplinary approach, this study investigates and analyzes drug delivery and release strategies in the nanoparticle-based treatment of cancer, both mathematically and clinically.

The worldwide misuse of antibiotics and the subsequent rise of multidrug-resistant pathogenic bacteria have prompted a paradigm shift in the established view of antibiotic and bacterial-human relations. The clinical failures of conventional antibiotic therapies are associated with lengthy detection methods, poor penetration at infection sites, disruption of indigenous microflora and high potential for mutational resistance. One of the most promising strategies to improve the efficacy of antibiotics is to complex them with micro or nano delivery materials. Such materials/vehicles can shield antibiotics from enzyme deactivation, increasing the therapeutic effectiveness of the drug. Alternatively, drug-free nanomaterials that do not kill the pathogen but target virulent factors such as adhesins, toxins, or secretory systems can be used to minimize resistance and infection severity. The main objective of this review is to examine the potential of the aforementioned materials in the detection and treatment of antibiotic-resistant pathogenic organisms.

Numerous nano drug delivery systems have been developed for preclinical cancer research in the past 15 years with the hope for a fundamental change in oncology. The robust nanotherapeutic research has yielded early-stage clinical products as exemplified by the FDA-approved nano formulations (Abraxane® for paclitaxel and Onyvide® for irinotecan) for the treatment of solid tumors, including pancreatic ductal adenocarcinoma (PDAC). It is generally believed that enhanced permeability and retention (EPR) plays a key role in nanocarriers' accumulation in preclinical tumor models and is a clinically relevant phenomenon in certain cancer types. However, use of EPR effect as an across-the-board explanation for nanoparticle tumor access is likely over-simplified, particularly in the stroma rich solid tumors such as PDAC. Recently, ample evidences including our own data showed that it is possible to use transcytosis as a major mechanism for PDAC drug delivery. In this mini-review, we summarize the key studies that discuss how transcytosis can be employed to enhance EPR effect in PDAC, and potentially, other cancer malignancies. We also mentioned other vasculature engineering approaches that work beyond the classic EPR effect.

Wound healing is a multi-stage process during which a cascade of molecular and cellular events collaborate to restore the damaged tissue to its healthy state. The inability of the available therapies to effectively heal the wounds has imposed major problems on healthcare systems. Therefore, developing novel therapeutic modalities capable of enhancing wound healing process with no/or limited scar formation is of more importance. Different studies have investigated the potential of phytochemicals on the wound healing process. They have shown to exert anti-inflammatory, antioxidant, and antibacterial activities as well as promoting collagen synthesis and deposition, leading to enhancing wound healing. Nanotechnology, as an applicable knowledge, has provided versatile means to improve the efficiency and effectiveness of wound treatment. The application of nanoparticles has conferred various advantages in the field of wound treatment. They protect the therapeutics from degradation, release the cargo in a controlled fashion, possess healing properties, and can act as extracellular matrix (ECM) mimic. In this review, we discuss the naturally-occurring compounds with wound healing properties and their nano-formulation for skin wound therapy.

Human immunodeficiency virus (HIV) patients are often diagnosed in the chronic stage of HIV/AIDS. Combination antiretroviral therapy (cART) has improved quality of life for HIV-infected patients. Present study describes a novel long-acting parenteral formulation of combination antiretroviral (cARV) loaded nano-drugs for treating chronic HIV-1 (cHIV) in a humanized-BLT (hu-BLT) mice model. The cARV (elvitegravir+tenofovir alafenamide+emtricitabine; EVG+TAF+FTC) drugs (mimicking marketed Genvoya® one-pill for HIV-treatment) were encapsulated in poly (lactic-co-glycolic acid) nanoparticles (NPs). To establish cHIV, hu-BLT mice were intravaginally challenged with HIV-1 and maintained for 15 weeks. Plasma viral load (pVL) was monitored by RT-PCR to confirm cHIV. Baseline pVL (week 15) was comparable between treated (n = 10) and control (n = 5) mice groups. Subsequently, treatment hu-BLT mice received 3 subcutaneous doses of cARV NPs (417 mg/kg per dose; n = 10), biweekly, and a fourth/terminal dose a week later. Prior to each treatment and on sacrifice (week 24), pVL was determined. Within three subcutaneous doses of cARV NPs, a non-detectable pVL was established (week 19) and continued until week 22. After the establishment of a non-detectable pVL (week 19–22), 4 treated-mice were sacrificed for tissue drug concentration determination by LC-MS/MS analysis. A considerable amount of cARV was detected at the HIV-infection target and reservoir organs. Subsequently, pVL rebounded comparable to control group by week 24, (7 weeks post-terminal dosage). The present study demonstrated cARV NPs augments sustained ARV efficacy in the cHIV humanized-mouse model. Therefore, cARV NPs could be a novel delivery system to treat cHIV patients, by overcoming drawbacks of conventional cART.

Theranostics is an emerging field which involves application of a single formulation for both diagnosis as well as therapeutics. The present manuscript describes various applications of hybrid mesoporous silica nanoparticles in therapeutics, diagnostics and in theranostics. In spite of advancement in medicine, early diagnosis and complete treatment of various diseases like cancers, HIV and diabetes still remains a daunting task. The answer to the treatment of these deadly diseases lies in the vast research done on smart functionally modified mesoporous silica nanoparticles. The promising results given by MSNs in various in vitro and in vivo studies, accounts for the overwhelming attention they are receiving in the field of drug delivery and diagnostics. Their effect on immune system has also been outlined. Applications are also being reported in the field of gene delivery. Due to wide applications, these multifunctional Nano carriers are befitted for the job of drug delivery and cell tracking. Their role as contrast agents in the field of diagnostics is also described. The manuscript focusses on construction strategies, applications, challenges and opportunities associated with this emerging Nano drug delivery technology. Though Mesoporous silica nanoparticles have already entered pre-clinical development stage, their testing in clinical trials on a large scale needs to be accomplished to establish their efficacy and safety in humans. The ultimate goal of these astute composite mesoporous carriers is to utilize diagnostic information for controlling their therapeutic function. Smart multifunctional MSNs have a great potential ahead and can be the answer to cure of various deadly diseases.

Over the past decade, there has been a rise in the number of clinical cases of moderate to severe anterior segment ocular diseases. Conventional topical ophthalmic formulations have several limitations – to address which, novel drug-delivery systems are needed. Additionally, formidable physiological barriers limit ocular bioavailability through the topical route of application. During the last decade, various nano-scaled ocular drug-delivery strategies have been reported. Some of these exploratory, topical, noninvasive approaches have shown promise in improving penetration into the anterior segment tissues of the eye. In this article, we review the available literature with respect to the safety, efficiency and effectiveness of these nano systems.

With the rapid development of nanotechnology, organelle-targeted nano drug delivery systems (NDDSs) have emerged as a potential method which can transport drugs specifically to the subcellular compartments like nucleus, mitochondrion, lysosome, endoplasmic reticulum (ER) and Golgi apparatus (GA). GA not only plays a key role in receiving, modifying, packaging and transporting proteins and lipids, but also contributes to a set of cellular processes. Golgi-targeted NDDSs can alter the morphology of GA and will become a promising strategy which achieves high specificity, low-dose administration and decreased occurrence of side effects. In this review, Golgi-targeted NDDSs and their applications in disease therapies and diagnosis such as cancer, metastasis, fibrosis and neurological diseases are introduced. Meanwhile, modifications of NDDSs to achieve targeting strategies, Golgi-disturbing agents to change the morphology of GA, special endocytosis to achieve endosomal/lysosomal escape strategies are also involved.

Cancer is the leading cause of human disease and death worldwide, accounting for 7.6 million deaths per year and projected to reach 13.1 million by 2030. Many phytochemicals included in traditional medicine have been utilized in the management of cancer. Conventional chemotherapy is generally known to be the most effective treatment of metastatic cancer but these cancerous cells might grow resistant to numerous anticancer drugs over time that resulting in treatment failure. This review tried to portray the advancement in the anticancer and chemopreventive effects of several phytochemicals and some of its members encapsulated in the nano-based delivery system of the drug. It comprises the issue associated with limited use of each phytoconstituents in human cancer treatment are discussed, and the benefits of entrapment into nanocarriers are evaluated in terms of drug loading efficiency, nanocarrier size, release profile of the drug, and in vitro and/or in vivo research and treatment testing, such as cytotoxicity assays and cell inhibition/viability.