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Cancer is ranked as the second leading cause of death globally. Traditional cancer therapies including chemotherapy are flawed, with off-target and on-target toxicities on the normal cells, requiring newer strategies to improve cell selective targeting. The application of nanomaterial has been extensively studied and explored as chemical biology tools in cancer theranostics. It shows greater applications toward stability, biocompatibility, and increased cell permeability, resulting in precise targeting, and mitigating the shortcomings of traditional cancer therapies. The nanoplatform offers an exciting opportunity to gain targeting strategies and multifunctionality. The advent of nanotechnology, in particular the development of smart nanomaterials, has transformed cancer diagnosis and treatment. The large surface area of nanoparticles is enough to encapsulate many molecules and the ability to functionalize with various biosubstrates such as DNA, RNA, aptamers, and antibodies, which helps in theranostic action. Comparatively, biologically derived nanomaterials perceive advantages over the nanomaterials produced by conventional methods in terms of economy, ease of production, and reduced toxicity. The present review summarizes various techniques in cancer theranostics and emphasizes the applications of smart nanomaterials (such as organic nanoparticles (NPs), inorganic NPs, and carbon-based NPs). We also critically discussed the advantages and challenges impeding their translation in cancer treatment and diagnostic applications. This review concludes that the use of smart nanomaterials could significantly improve cancer theranostics and will facilitate new dimensions for tumor detection and therapy.

Nano-sized materials have great potential as drug carriers for nanomedicine applications. Thanks to their size, they can exploit the cellular machinery to enter cells and be trafficked intracellularly, thus they can be used to overcome some of the cellular barriers to drug delivery. Nano-sized drug carriers of very different properties can be prepared, and their surface can be modified by the addition of targeting moieties to recognize specific cells. However, it is still difficult to understand how the material properties affect the subsequent interactions and outcomes at cellular level. As a consequence of this, designing targeted drugs remains a major challenge in drug delivery. Within this context, we discuss the current understanding of the initial steps in the interactions of nano-sized materials with cells in relation to nanomedicine applications. In particular, we focus on the difficult interplay between the initial adhesion of nano-sized materials to the cell surface, the potential recognition by cell receptors, and the subsequent mechanisms cells use to internalize them. The factors affecting these initial events are discussed. Then, we briefly describe the different pathways of endocytosis in cells and illustrate with some examples the challenges in understanding how nanomaterial properties, such as size, charge, and shape, affect the mechanisms cells use for their internalization. Technical difficulties in characterizing these mechanisms are presented. A better understanding of the first interactions of nano-sized materials with cells will help to design nanomedicines with improved targeting.

Nano-sized materials have great potential as drug carriers for nanomedicine applications. Thanks to their size, they can exploit the cellular machinery to enter cells and be trafficked intracellularly, thus they can be used to overcome some of the cellular barriers to drug delivery. Nano-sized drug carriers of very different properties can be prepared, and their surface can be modified by the addition of targeting moieties to recognize specific cells. However, it is still difficult to understand how the material properties affect the subsequent interactions and outcomes at cellular level. As a consequence of this, designing targeted drugs remains a major challenge in drug delivery. Within this context, we discuss the current understanding of the initial steps in the interactions of nano-sized materials with cells in relation to nanomedicine applications. In particular, we focus on the difficult interplay between the initial adhesion of nano-sized materials to the cell surface, the potential recognition by cell receptors, and the subsequent mechanisms cells use to internalize them. The factors affecting these initial events are discussed. Then, we briefly describe the different pathways of endocytosis in cells and illustrate with some examples the challenges in understanding how nanomaterial properties, such as size, charge, and shape, affect the mechanisms cells use for their internalization. Technical difficulties in characterizing these mechanisms are presented. A better understanding of the first interactions of nano-sized materials with cells will help to design nanomedicines with improved targeting.

Background: Colorectal cancer (CRC) is the third most prevalent type of cancer for incidence and second for mortality worldwide. Late diagnosis and inconvenient and expensive current diagnostic tools largely contribute to the progress of the disease. The use of chemotherapy in the management of CRC significantly reduces tumor growth, metastasis, and morbidity rates. However, poor solubility, low cellular uptake, nonspecific distribution, multiple drug resistance and unwanted adverse effects are still among the major drawbacks of chemotherapy that limit its clinical significance in the treatment of CRC. Owing to their remarkable advantages over conventional therapies, the use of nanotechnology-based delivery systems especially polymeric nanocarriers (PNCs) has revolutionized many fields including disease diagnosis and drug delivery.Aim of Review: In this review, we shed the light on the current status of using PNCs in the diagnosis and treatment of CRC with a special focus on targeting strategies, surface modifications and safety concerns for different types of PNCs in colonic cancer delivery.Key Scientific Concepts of Review: The review explores the current progress on the use of PNCs in the diagnosis and treatment of CRC with a special focus on the role of PNCs in improvement of cellular uptake, drug targeting and co-delivery of chemotherapeutic agents. Possible toxicity and biocompatibility issues related to the use of PNCs and imitations and future recommendation for the use of those smart carriers in the diagnosis and treatment of CRC are also discussed. Acknowledgement This research was supported by Univeristy of Sharjah (UOS) tar-geted research project funds, 2101110345 to MH.

Conventional therapies for cancer eradication like surgery, radiotherapy, and chemotherapy, even though most widely used, still suffer from some disappointing outcomes. The limitations of these therapies during cancer recurrence and metastasis demonstrate the need for better alternatives. Some bacteria preferentially colonize and proliferate inside tumor mass; thus these bacteria can be used as ideal candidates to deliver antitumor therapeutic agents. The bacteria like Bacillus spp., Clostridium spp., E. coli, Listeria spp., and Salmonella spp. can be reprogrammed to produce, transport, and deliver anticancer agents, eg, cytotoxic agents, prodrug converting enzymes, immunomodulators, tumor stroma targeting agents, siRNA, and drug-loaded nanoformulations based on clinical requirements. In addition, these bacteria can be genetically modified to express various functional proteins and targeting ligands that can enhance the targeting approach and controlled drug-delivery. Low tumor-targeting and weak penetration power deep inside the tumor mass limits the use of anticancer drug-nanoformulations. By using anticancer drug nanoformulations and other therapeutic payloads in combination with antitumor bacteria, it makes a synergistic effect against cancer by overcoming the individual limitations. The tumor-targeting bacteria can be either used as a monotherapy or in addition with other anticancer therapies like photothermal therapy, photodynamic therapy, and magnetic field therapy to accomplish better clinical outcomes. The toxicity issues on normal tissues is the main concern regarding the use of engineered antitumor bacteria, which requires deeper research. In this article, the mechanism by which bacteria sense tumor microenvironment, role of some anticancer agents, and the recent advancement of engineering bacteria with different therapeutic payloads to combat cancers has been reviewed. In addition, future prospective and some clinical trials are also discussed.

Precise methods for quantifying drug accumulation in brain tissue are currently very limited, challenging the development of new therapeutics for brain disorders. Transcardial perfusion is instrumental for removing the intravascular fraction of an injected compound, thereby allowing for ex vivo assessment of extravasation into the brain. However, pathological remodeling of tissue microenvironment can affect the efficiency of transcardial perfusion, which has been largely overlooked. We show that, in contrast to healthy vasculature, transcardial perfusion cannot remove an injected compound from the tumor vasculature to a sufficient extent leading to considerable overestimation of compound extravasation. We demonstrate that 3D deep imaging of optically cleared tumor samples overcomes this limitation. We developed two machine learning-based semi-automated image analysis workflows, which provide detailed quantitative characterization of compound extravasation patterns as well as tumor angioarchitecture in large three-dimensional datasets from optically cleared samples. This methodology provides a precise and comprehensive analysis of extravasation in brain tumors and allows for correlation of extravasation patterns with specific features of the heterogeneous brain tumor vasculature., Kostrikov et al. report a deficiency of transcardial perfusion in brain tumor vasculature, which leads to exaggeration of drug extravasation measurements. They then demonstrate how optical tissue clearing can help to overcome this limitation and provide two machine learning-based image analysis workflows enabling detailed quantitative characterization of compound extravasation patterns as well as tumor angioarchitecture in large three-dimensional datasets.

During the last couple of decades considerable research efforts have been directed towards the synthesis and coating of iron oxide nanoparticles (IONPs) for biomedical applications. To address the current limitations, recent studies have focused on the design of new generation nanoparticle systems whose internalization and targeting capabilities have been improved through surface modifications. This review covers the most recent challenges and advances in the development of IONPs with enhanced quality, and biocompatibility for various applications in biotechnology and medicine., NA

Water-soluble, nano-sized crosslinked polymer networks, or nanogels, are delivery vehicles, which have highly interesting properties for therapeutic delivery and imaging. Nanogels may also possess responsive properties, depending on the employed polymers, allowing controlled release of therapeutics or image contrast generation upon exposure to physical or (bio) chemical cues. In this review, polymer nanogels are explored for application in imaging as well as for controlled drug and gene delivery. Moreover, nanogels are explored as responsive biomaterials and future applications are highlighted.

Active targeted nanotechnology-based drug delivery systems have gained significant favor because they have the ability to decrease side effects, improve drug bioavailability, and the potency of anticancer treatment. In this study, functional amphiphilic Janus nanoparticles (JNPs), consisting of hydrophilic and hydrophobic biocompatible polymers as two distinct sides, have been prepared via a robust and simple synthesis method. The surface-active hydrophilic side of this Janus platform is functionalized with an aptamer against epithelial cell adhesion molecule (EpCAM) to deliver Doxorubicin (DOX) for the treatment of metastasis colorectal adenocarcinoma HT29 cells. The Janus morphology of the nanoparticles and their cell penetration behavior are shown in microscopic evaluations. By evaluating the prepared DOX-loaded aptamer–modified JNPs by cell-toxicity assay and confocal microscopy, it was determined that the utilization of an internalization strategy to enhance cell uptake would increase the anticancer effect of the Janus nanocarrier and improve the capacity to deliver the chemotherapeutical drug site-specifically.

Water-soluble, nano-sized crosslinked polymer networks, or nanogels, are delivery vehicles, which have highly interesting properties for therapeutic delivery and imaging. Nanogels may also possess responsive properties, depending on the employed polymers, allowing controlled release of therapeutics or image contrast generation upon exposure to physical or (bio) chemical cues. In this review, polymer nanogels are explored for application in imaging as well as for controlled drug and gene delivery. Moreover, nanogels are explored as responsive biomaterials and future applications are highlighted.

Rapidly evolving technical and regulatory landscapes of the pharmaceutical product development necessitates risk management with application of multivariate analysis using Process Analytical Technology (PAT) and Quality by Design (QbD). Poorly soluble, high dose drug, Satranidazole was optimally nanoprecipitated (SAT-NP) employing principles of Formulation by Design (FbD). The potential risk factors influencing the critical quality attributes (CQA) of SAT-NP were identified using Ishikawa diagram. Plackett-Burman screening design was adopted to screen the eight critical formulation and process parameters influencing the mean particle size, zeta potential and dissolution efficiency at 30 min in pH 7.4 dissolution medium. Pareto charts (individual and cumulative) revealed three most critical factors influencing CQA of SAT-NP viz. aqueous stabilizer (Polyvinyl alcohol), release modifier (Eudragit (R) S 100) and volume of aqueous phase. The levels of these three critical formulation attributes were optimized by FbD within established design space to minimize mean particle size, poly dispersity index, and maximize encapsulation efficiency of SAT-NP. Lenth's and Bayesian analysis along with mathematical modeling of results allowed identification and quantification of critical formulation attributes significantly active on the selected CQAs. The optimized SAT-NP exhibited mean particle size; 216 nm, polydispersity index; 0.250, zeta potential; -3.75 mV and encapsulation efficiency; 78.3%. The product was lyophilized using mannitol to form readily redispersible powder. X-ray diffraction analysis confirmed the conversion of crystalline SAT to amorphous form. In vitro release of SAT-NP in gradually pH changing media showed

Autoimmunity develops when self-tolerance mechanisms are failing to protect healthy tissue. A sustained reaction to self is generated, which includes the generation of effector cells and molecules that destroy tissues. A way to restore this intrinsic tolerance is through immune modulation that aims at refurbishing this immunologically naive or unresponsive state, thereby decreasing the aberrant immune reaction taking place. One major cytokine has been shown to play a pivotal role in several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS): tumor necrosis factor alpha (TNF alpha) modulates the induction and maintenance of an inflammatory process and it comes in two variants, soluble TNF (solTNF) and transmembrane bound TNF (tmTNF). tmTNF signals via TNFR1 and TNFR2, whereas solTNF signals mainly via TNFR1. TNFR1 is widely expressed and promotes mainly inflammation and apoptosis. Conversely, TNFR2 is restricted mainly to immune and endothelial cells and it is known to activate the pro-survival PI3K-Akt/PKB signaling pathway and to sustain regulatory T cells function. Anti-TNF alpha therapies are successfully used to treat diseases such as RA, colitis, and psoriasis. However, clinical studies with a non-selective inhibitor of TNFa in MS patients had to be halted due to exacerbation of clinical symptoms. One possible explanation for this failure is the non-selectivity of the treatment, which avoids TNFR2 stimulation and its immune and tissue protective properties. Thus, a receptor-selective modulation of TNFa signal pathways provides a novel therapeutic concept that might lead to new insights in MS pathology with major implications for its effective treatment.

Autoimmunity develops when self-tolerance mechanisms are failing to protect healthy tissue. A sustained reaction to self is generated, which includes the generation of effector cells and molecules that destroy tissues. A way to restore this intrinsic tolerance is through immune modulation that aims at refurbishing this immunologically naive or unresponsive state, thereby decreasing the aberrant immune reaction taking place. One major cytokine has been shown to play a pivotal role in several autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS): tumor necrosis factor alpha (TNF alpha) modulates the induction and maintenance of an inflammatory process and it comes in two variants, soluble TNF (solTNF) and transmembrane bound TNF (tmTNF). tmTNF signals via TNFR1 and TNFR2, whereas solTNF signals mainly via TNFR1. TNFR1 is widely expressed and promotes mainly inflammation and apoptosis. Conversely, TNFR2 is restricted mainly to immune and endothelial cells and it is known to activate the pro-survival PI3K-Akt/PKB signaling pathway and to sustain regulatory T cells function. Anti-TNF alpha therapies are successfully used to treat diseases such as RA, colitis, and psoriasis. However, clinical studies with a non-selective inhibitor of TNFa in MS patients had to be halted due to exacerbation of clinical symptoms. One possible explanation for this failure is the non-selectivity of the treatment, which avoids TNFR2 stimulation and its immune and tissue protective properties. Thus, a receptor-selective modulation of TNFa signal pathways provides a novel therapeutic concept that might lead to new insights in MS pathology with major implications for its effective treatment.

Therapies directed toward the central nervous system remain difficult to translate into improved clinical outcomes. This is largely due to the blood–brain barrier (BBB), arguably the most tightly regulated interface in the human body, which routinely excludes most therapeutics. Advances in the engineering of nanomaterials and their application in biomedicine (i.e., nanomedicine) are enabling new strategies that have the potential to help improve our understanding and treatment of neurological diseases. Herein, the various mechanisms by which therapeutics can be delivered to the brain are examined and key challenges facing translation of this research from benchtop to bedside are highlighted. Following a contextual overview of the BBB anatomy and physiology in both healthy and diseased states, relevant therapeutic strategies for bypassing and crossing the BBB are discussed. The focus here is especially on nanomaterial‐based drug delivery systems and the potential of these to overcome the biological challenges imposed by the BBB. Finally, disease‐targeting strategies and clearance mechanisms are explored. The objective is to provide the diverse range of researchers active in the field (e.g., material scientists, chemists, engineers, neuroscientists, and clinicians) with an easily accessible guide to the key opportunities and challenges currently facing the nanomaterial‐mediated treatment of neurological diseases.

Targeting angiogenesis-related pathologies, which include tumorigenesis and metastatic processes, has become an attractive strategy for the development of efficient guided nanomedicines. In this respect, integrins are cell-adhesion molecules involved in angiogenesis signaling pathways and are overexpressed in many angiogenic processes. Therefore, they represent specific biomarkers not only to monitor disease progression but also to rationally design targeted nanomedicines. Arginine-glycine-aspartic (RGD) containing peptides that bind to specific integrins have been widely utilized to provide ligand-mediated targeting capabilities to small molecules, peptides, proteins, and antibodies, as well as to drug/imaging agent-containing nanomedicines, with the final aim of maximizing their therapeutic index. Within this review, we aim to cover recent and relevant examples of different integrin-assisted nanosystems including polymeric nanoconstructs, liposomes, and inorganic nano particles applied in drug/gene therapy as well as imaging and theranostics. We will also critically address the overall benefits of integrin-targeting. (C) 2017 Elsevier B.V. All rights reserved.

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic., This work was supported by the Deutscher Akademischer Austauschdienst (DAAD to Philipps Universität Marburg and Zhejiang University, Hangzhou), the Chinesisch Deutsches Zentrum für Wissenschaftsförderung (“CDZ” to Z.G. and W.J.P.), and the Chinese Academy of Science (CAS). Part of this work was supported by the National Natural Science Foundation (51390481, 81227902, 81625011), National Basic Research Program (2014CB931900) of China (to Y.S.), by the European Commission grant Futurenanoneeds (to V.P. and W.J.P.), by the Spanish Ministerio de Economia y Competitividad (CTQ2011-23167 and CTQ2014-59808R to R.A.A.P.), the Generalitat of Catalunya (2014-SGR-612 to R.A.A.P.), the Deutsche Forschungsgemeinschaft (DFG) (AL552/8-1 to R.T.), the Swiss National Science Foundation (NRP62 to P.H.), the Claude & Julianna Foundation (grant to P.H.), the National Science Foundation (NSF) grants CHE-1306928 (to R.P.) and ECS-0601345; CBET 0933384; CBET 0932823; and CBET 1036672 (to N.A.K.), Canadian Institute of Health Research (grant to W.C.W.C.), and Natural Sciences and Engineering Research Council of Canada (grant to W.C.W.C.). S.A. and B.P. acknowledge a fellowship from the Alexander von Humboldt Foundation. N.F. acknowledges the Lars Hiertas Minne Foundation. M.C. acknowledges Ikerbasque for a Research Fellow position. X.C. acknowledges the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). B.Z.T. acknowledges the Innovation and Technology Commission of Hong Kong (ITC-CNERC14SC01). The Pancreatic Cancer research of A.E.N. and H.M. was funded by the U.S. National Cancer Institute, NIH grant # U01CA198846. A.E. acknowledges Junta de Andalucía (Spain) for a Talentia Postdoc Fellowship, co-financed by the European Union's Seventh Framework Programme, grant agreement no 267226. A.G.S. acknowledges support by BOF (UGent) and FWO (Research Foundation Flanders). Part of this work was supported by the National Natural Science Foundation of China.

A comparative study has been done on the drug loading efficacy of different surface functionalized Fe3O4 magnetic nanoparticles (MNP) and their effect toward ovarian cancer cell line (HeLa) in vitro. The surface coating was done with carboxyl group enriched organic ligands such as succinic acid, L-arginine, oxalic acid, citric acid and glutamic acid. A maximum of similar to 62 wt.% drug has been loaded in oxalic acid coated MNP whereas least (similar to 35 wt.%) in arginine coated MNP due to variation in the chemistry of surface active agents. The cytotoxicity of functionalized MNP and doxorubicin loaded MNP were studied. The functionalized MNP are quite biocompatible whereas they show cytotoxic effect in HeLa cells e.g., around 35% cell death when treated with oxalic acid coated MNP at a concentration of similar to 100 mu g/ml. The cell death was triggered in drug loaded particle and almost complete cell death i.e., >90% was observed in oxalic acid coated MNP followed by similar to 80% and similar to 70% death in arginine and succinic acid coated MNP, respectively.

Designing bioresponsive nanocarriers for controlled and efficient intracellular drug release for cancer therapy is a major thrust area in nanomedicine. With recent recognition by the US FDA as a safe material for human trials, mesoporous silica nanoparticles (MSNPs) are being extensively explored as promising theranostic agents. Green fluorescent carbon quantum dots (CQDs), though known as possible alternatives for their more toxic and relatively less efficient predecessors, are less known as gate keepers for drug release control. We report for the first time an efficient bioresponse of CQDs when judiciously designed using glutathione cleavable (redox responsive) disulphide bonds. When the anticancer drug doxorubicin loaded MSNPs are capped with these CQDs, they display promising drug release control on exposure to a mimicked intracellular cancer environment. Their dual functionality is well established with good control on preventing the premature release and exceptional bio-imaging of HeLa cancer cells. Fluorescence images prove selective targeting of HeLa cells by overexpression of folate receptors from the surface functionalised folic acid ligand. Extensive characterisation using XRD, TEM, BET analysis, drug loading tests, drug release kinetics, MTT assay and fluoroscence cell imaging helps in understanding the multi-functionalities of the successful design, extending its scope with exciting prospects towards non-invasive targeted drug delivery and bio-imaging for effective cancer diagnosis and treatment.

Among the several types of inorganic nanoparticles available, silica nanoparticles (SNP) have earned their relevance in biological applications namely, as bioimaging agents. In fact, fluorescent SNP (FSNP) have been explored in this field as protective nanocarriers, overcoming some limitations presented by conventional organic dyes such as high photobleaching rates. A crucial aspect on the use of fluorescent SNP relates to their surface properties, since it determines the extent of interaction between nanoparticles and biological systems, namely in terms of colloidal stability in water, cellular recognition and internalization, tracking, biodistribution and specificity, among others. Therefore, it is imperative to understand the mechanisms underlying the interaction between biosystems and the SNP surfaces, making surface functionalization a relevant step in order to take full advantage of particle properties. The versatility of the surface chemistry on silica platforms, together with the intrinsic hydrophilicity and biocompatibility, make these systems suitable for bioimaging applications, such as those mentioned in this review.

International audience; Self-assembly of a series of amphiphilic poly(oligo(ethylene glycol) methyl ether methacrylate)-block-poly(lactic acid)-block-poly(oligo(ethylene glycol) methyl ether methacrylate) (P(OEGMA)-b-PLLA-b-P(OEGMA)) copolymers was investigated. The copolymers were synthesized by a combination of ring-opening polymerization (ROP) of L-lactide and atom transfer radical polymerization (ATRP) of oligo ethylene glycol methyl ether methacrylate (OEGMA). The resulting brush-like triblock copolymers were characterized by H-1 NMR and size exclusion chromatography. Self-assembly behavior of the copolymers in deionized water was investigated by fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). The critical aggregation concentration ranged from 50 to 160 mg L-1 depending on the composition. The diameter of the nanoparticles (NPs) was determined by DLS and TEM. Images showed that these nano-sized objects displayed spherical and worm-like morphology with a length increasing with the hydrophilic content. Preliminary studies of drug loading and drug release with a water-insoluble model drug, namely curcumin, showed that these NPs are potential candidates for drug delivery carriers.

Accurate cancer diagnosis often requires extraction and purification of genetic materials from cells, and sophisticated instrumentations that follow. Otherwise in order to directly treat the diagnostic materials to cells, multiple steps to optimize dose concentration and treatment time are necessary due to diversity in cellular behaviors. These processes may offer high precision but hinder fast analysis of cancer, especially in clinical situations that need rapid detection and characterization of cancer. Here we present a novel fluorescent tile DNA nanostructure delivered to cancer cytosol by employing nanoparticle technology. Its structural anisotropicity offers easy manipulation for multifunctionalities, enabling the novel DNA nanostructure to detect intracellular cancer RNA markers with high specificity within 30 minutes post treatment, while the nanoparticle property bypasses the requirement of treatment optimization, effectively reducing the complexity of applying the system for cancer diagnosis. Altogether, the system offers a precise and rapid detection of cancer, suggesting the future use in the clinical fields. Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C3301]; Basic Science Research Programs through the National Research Foundation (NRF) - Ministry of Science ICT and Future Planning [2013R1A1A1058670, 2013R1A1A2016781]; Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning (MSIP) [2013K1A4A3055268] We especially thank Mr. Woo Chul Song for his ardent help and discussion. This work was supported by grants from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HI14C3301) and by Basic Science Research Programs through the National Research Foundation (NRF) funded by the Ministry of Science ICT and Future Planning (Grant Nos. 2013R1A1A1058670 and 2013R1A1A2016781) and by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (MSIP) (2013K1A4A3055268).

Fibrosis is the common end point of chronic kidney disease. The persistent production of inflammatory cytokines and growth factors leads to an ongoing process of extracellular matrix production that eventually disrupts the normal functioning of the organ. During fibrosis, the myofibroblast is commonly regarded as the predominant effector cell. Accumulating evidence has demonstrated a diverse origin of myofibroblasts in kidney fibrosis. Proposed major contributors of myofibroblasts include bone marrow-derived fibroblasts, tubular epithelial cells, endothelial cells, pericytes and interstitial fibroblasts; the published data, however, have not yet clearly defined the relative contribution of these different cellular sources. Myofibroblasts have been reported to originate from various sources, irrespective of the nature of the initial damage responsible for the induction of kidney fibrosis. Here, we review the possible relevance of the diversity of myofibroblast progenitors in kidney fibrosis and the implications for the development of novel therapeutic approaches. Specifically, we discuss the current status of preclinical and clinical antifibrotic therapy and describe targeting strategies that might help support resident and circulating cells to maintain or regain their original functional differentiation state. Such strategies might help these cells resist their transition to a myofibroblast phenotype to prevent, or even reverse, the fibrotic state.

Biocompatible or biodegradable hyperbranched polymers (HBPs), an important subclass of hyperbranched macromolecules, have recently received an increasing attention due to their unique physical and chemical properties as well as their great advantages in therapeutic applications. This review highlights recent advances and future trends in the preparation and applications of biocompatible or biodegradable HBPs for therapeutic purpose. Various biocompatible or biodegradable hyperbranched structures can be obtained by means of step-growth polycondensation (SGP), self-condensing vinyl polymerization (SCVP), self-condensing ring-opening polymerization (SCROP), and so forth. The properties of biocompatible or biodegradable HBPs can be tailored for a specialized purpose through terminal modification, backbone modification, or hybrid modification. A particular emphasis is then placed on their diagnostic, therapeutic delivery and theranostic applications. Finally, future directions and perspectives in this emerging field are briefly discussed. These developments on synthesis and therapeutic applications of biocompatible or biodegradable HBPs promote the interdisciplinary research spanning polymer materials and biomedical sciences.