Polymeric nanocarriers for cancer theranostics

Theranostics is an emerging area in nanomedicine where therapeutic and diagnostic platforms are integrated together to perform multiple functions such as disease diagnostic and therapy, noninvasive method to determine the targeted delivery of drugs, and evaluation of drug efficacy. This review gives an overview of the different therapeutic and diagnostic strategies used to construct a theranostic system. The importance of polymer‐based theranostic carriers is presented. The different types of polymeric carriers such as micelles, liposomes, dendrimers, and nanogels explored for theranostic applications are also presented. Copyright © 2017 John Wiley & Sons, Ltd.     

Advanced drug delivery systems: Nanotechnology of health design A review

Nanotechnology has finally and firmly entered the realm of drug delivery. Performances of intelligent drug delivery systems are continuously improved with the purpose to maximize therapeutic activity and to minimize undesirable side-effects. This review describes the advanced drug delivery systems based on micelles, polymeric nanoparticles, and dendrimers. Polymeric carbon nanotubes and many others demonstrate a broad variety of useful properties. This review emphasizes the main requirements for developing new nanotech-nology-based drug delivery systems.     

Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives

In the past decade, nanomedicine with its promise of improved therapy and diagnostics has revolutionized conventional health care and medical technology. Dendrimers and dendrimer-based therapeutics are outstanding candidates in this exciting field as more and more biological systems have benefited from these starburst molecules. Anticancer agents can be either encapsulated in or conjugated to dendrimer and be delivered to the tumour via enhanced permeability and retention (EPR) effect of the nanoparticle and/or with the help of a targeting moiety such as antibody, peptides, vitamins, and hormones. Imaging agents including MRI contrast agents, radionuclide probes, computed tomography contrast agents, and fluorescent dyes are combined with the multifunctional nanomedicine for targeted therapy with simultaneous cancer diagnosis. However, an important question reported with dendrimer-based therapeutics as well as other nanomedicines to date is the long-term viability and biocompatibility of the nanotherapeutics. This critical review focuses on the design of biocompatible dendrimers for cancer diagnosis and therapy. The biocompatibility aspects of dendrimers such as nanotoxicity, long-term circulation, and degradation are discussed. The construction of novel dendrimers with biocompatible components, and the surface modification of commercially available dendrimers by PEGylation, acetylation, glycosylation, and amino acid functionalization have been proposed as available strategies to solve the safety problem of dendrimer-based nanotherapeutics. Also, exciting opportunities and challenges on the development of dendrimer-based nanoplatforms for targeted cancer diagnosis and therapy are reviewed (404 references).     

Recent progress in cationic polymeric gene carriers for cancer therapy

In recent years,various carriers for gene delivery nave been developed for biomedical applications.Among all kinds of gene carriers,cationic polymeric carriers for delivery therapeutic gene as non-viral carriers have received growing interests due to their improved high transfection efficiency with the relative safety.In particular,the advancement of novel polymeric gene carriers has gained much progress in the development of effective anticancer therapy.Herein,this review focused on the development of cationic polymeric carriers for cancer therapy,including polyethylenimine(PEI),polyamidoamine(PAMAM) dendrimers,polylysine(PLL),chitosan and modified cationic polymers.And recent progresses in the development of novel polymeric carriers for gene delivery,such as targeted gene carriers,responsive gene carriers and multifunctional gene carriers,were summarized.Finally,the future perspectives in the development of novel polymeric carriers for delivery gene were presented.     

Biomarkers for Alzheimer's Disease – An Overview

Alzheimer's disease (AD) is a complex neurodegenerative disorder with a significant global impact on public health. The emergence of atypical clinical phenotypes challenges traditional diagnostic approaches, necessitating a deeper exploration of biomarkers for accurate identification. The US Food and Drug Administration (FDA) classification of biomarkers and their integration into different stages of AD provide a structured framework for their application in research and clinical settings. Within the context of AD drug development, biomarkers are essential for participant selection, target engagement evaluation, and assessment of pathological hallmarks, including Aβ and tau protein abnormalities. The incorporation of nanoparticles with a biodegradable approach introduces innovative strategies to address the complexities of AD. This paper extensively discusses biomarkers associated with synaptic dysfunction, neuroinflammation, and glial activation, recognizing their significance in elucidating disease mechanisms. Common pathologies such as synuclein and TDP-43 further underscore the multifaceted nature of AD. Current biomarkers for AD diagnosis, encompassing cerebral spinal fluid (CSF) biomarkers and various imaging modalities, reflect the ongoing efforts to enhance early detection and monitoring. Intriguingly, novel biomarkers continue to emerge, offering promising avenues for improved understanding and intervention. Current review provides a comprehensive survey of biomarkers for AD, elucidating their diverse roles across different aspects of the disease. By highlighting their contributions to diagnosis, drug development, and mechanistic insights, this overview underscores the importance of biomarker research in the pursuit of effective AD management and treatment strategies.     

Nanomaterials toward the treatment of Alzheimer's disease:Recent advances and future trends

Alzheimer's disease(AD) is a progressive and fatal neurodegenerative condition and the most prevalent cause of dementia. This disease is characterized by progressive cognitive impairment. The prevalence of AD is currently affecting more than 35 million people and is rising worldwide. No efficient therapy is currently available due to low drug potency and a number of various obstacles to delivery. Recent nanotechnological advancements have the potential to offer promising therapeutic options. Progress on nanomaterials as well as their applications in biomedicine is receiving increasing attention, especially the advantages of nanomaterial-based drug delivery systems. The aim of this review is to comprehensively summarize the latest developments in nanomaterial-based strategies for AD treatment, including nanoparticles, liposomes and other options for the delivery of therapeutic compounds and scaffolds for cell delivery strategies. Future research directions are also proposed. We hope this review can provide important information to guide the future development of nanomaterials in AD treatment.     

Dendrimer-based prodrugs: design, synthesis, screening and biological evaluation

Dendrimers are a new class of artificial macromolecules with well-defined hyperbranched structures which enable bio-active molecules such as drugs to be presented in a highly multi-valent fashion. Covalent conjugation of drugs to the surface of dendrimers can be easily achieved either by direct chemical reactions between dendrimers and drug molecules including esterification and amidation or through cleavable linkers, depending on the functional groups on the surface of dendrimers. The pharmacological properties of these dendrimer-based prodrugs such as biocompatibility, biodistribution, biostability, bioadhesion and biopermeability can be modulated by further modifying dendrimers with specific functional molecules to fit a specific medicinal purpose. In this mini-review, recent advances on the use of dendrimers as prodrug nano-scaffolds were briefly demonstrated. The design and synthesis of dendrimer-based prodrugs as well as screening their intrinsic properties in biological systems were fully discussed.     

聚合物纳米药物载体的研究进展

近年来, 大量研究结果表明纳米技术可显著提高传统药物的疾病治疗效果, 并在生物医学领域引起了广泛关注. 迄今, 多种聚合物纳米体系已被研发并用于药物的靶向递送. 随着纳米技术的不断发展, 各类生物微环境响应的功能基团也被应用于构筑新型药物载体, 以提高患病部位的药物富集及减少药物的毒副作用. 聚合物纳米药物载体在癌症治疗、 代谢类疾病治疗及抗菌等方面展现出巨大潜力. 本文系统评述了聚合物纳米药物载体的最新研究进展及在生物医药方面的应用.     

Targeted polymeric therapeutic nanoparticles: design, development and clinical translation

Polymeric materials have been used in a range of pharmaceutical and biotechnology products for more than 40 years. These materials have evolved from their earlier use as biodegradable products such as resorbable sutures, orthopaedic implants, macroscale and microscale drug delivery systems such as microparticles and wafers used as controlled drug release depots, to multifunctional nanoparticles (NPs) capable of targeting, and controlled release of therapeutic and diagnostic agents. These newer generations of targeted and controlled release polymeric NPs are now engineered to navigate the complex in vivo environment, and incorporate functionalities for achieving target specificity, control of drug concentration and exposure kinetics at the tissue, cell, and subcellular levels. Indeed this optimization of drug pharmacology as aided by careful design of multifunctional NPs can lead to improved drug safety and efficacy, and may be complimentary to drug enhancements that are traditionally achieved by medicinal chemistry. In this regard, polymeric NPs have the potential to result in a highly differentiated new class of therapeutics, distinct from the original active drugs used in their composition, and distinct from first generation NPs that largely facilitated drug formulation. A greater flexibility in the design of drug molecules themselves may also be facilitated following their incorporation into NPs, as drug properties (solubility, metabolism, plasma binding, biodistribution, target tissue accumulation) will no longer be constrained to the same extent by drug chemical composition, but also become in-part the function of the physicochemical properties of the NP. The combination of optimally designed drugs with optimally engineered polymeric NPs opens up the possibility of improved clinical outcomes that may not be achievable with the administration of drugs in their conventional form. In this critical review, we aim to provide insights into the design and development of targeted polymeric NPs and to highlight the challenges associated with the engineering of this novel class of therapeutics, including considerations of NP design optimization, development and biophysicochemical properties. Additionally, we highlight some recent examples from the literature, which demonstrate current trends and novel concepts in both the design and utility of targeted polymeric NPs (444 references).     

POSS基树枝状大分子的合成与应用

树枝状大分子(dendrimer)是一种高度支化、纳米尺度的人工合成大分子,具有独特的物理化学性能和重要的应用前景。利用具有8个可官能化顶点的多面体低聚倍半硅氧烷(POSS)作为树枝状大分子的核心,可在一定程度上简化树枝状大分子繁琐的合成与分离过程,在低代数时就可获得较大的表面官能团密度,并使树枝状分子呈现球形对称结构。POSS基树枝状大分子结合了POSS和树枝状分子结构与性能的优势,是一类极具潜力的有机-无机纳米杂化材料。本文综述了近年来POSS基树枝状大分子的最新研究成果,介绍了具有代表性的POSS基树枝状大分子的合成方法以及它们在催化剂、生物材料、液晶材料和发光材料等领域的应用研究进展,并对该新型材料的发展趋势做了展望。     

Detection of Aβ Monomers and Oligomers: Early Diagnosis of Alzheimer's Disease

Alzheimer's disease (AD), as the most common progressive neurodegenerative disorder, is pathologically characterized by deposition of extracellular plaque composed of amyloid‐β peptide (Aβ). Different assembled states of Aβ have been considered as both important biomarkers and drug targets for the diagnosis and therapy of AD. Recent studies demonstrate that small, diffusible Aβ oligomers formed by aggregation of Aβ monomers are the major toxic agents in AD. Therefore, the development of reliable assays for Aβ (both monomers and oligomers) will be important for the early differential diagnosis of dementia, predicting the progression of AD, as well as monitoring the effectiveness of novel anti‐Aβ drugs for AD. In this review, we summarize the recent progress made in the development of techniques for detection of Aβ monomers and oligomers. In particular, the principles governing the design of these sensors are classified and summarized. Moreover, the advantages and disadvantages of the assays are evaluated. This review also discusses the improvements and challenges for application of these assays in the early diagnosis of AD.     

Prospects of Curcumin Nanoformulations in Cancer Management

There is increasing interest in the use of natural compounds with beneficial pharmacological effects for managing diseases. Curcumin (CUR) is a phytochemical that is reportedly effective against some cancers through its ability to regulate signaling pathways and protein expression in cancer development and progression. Unfortunately, its use is limited due to its hydrophobicity, low bioavailability, chemical instability, photodegradation, and fast metabolism. Nanoparticles (NPs) are drug delivery systems that can increase the bioavailability of hydrophobic drugs and improve drug targeting to cancer cells via different mechanisms and formulation techniques. In this review, we have discussed various CUR-NPs that have been evaluated for their potential use in treating cancers. Formulations reviewed include lipid, gold, zinc oxide, magnetic, polymeric, and silica NPs, as well as micelles, dendrimers, nanogels, cyclodextrin complexes, and liposomes, with an emphasis on their formulation and characteristics. CUR incorporation into the NPs enhanced its pharmaceutical and therapeutic significance with respect to solubility, absorption, bioavailability, stability, plasma half-life, targeted delivery, and anticancer effect. Our review shows that several CUR-NPs have promising anticancer activity; however, clinical reports on them are limited. We believe that clinical trials must be conducted on CUR-NPs to ensure their effective translation into clinical applications.     

Stem cell therapy for Alzheimer's disease and related disorders: current status and future perspectives

Underlying cognitive declines in Alzheimer''s disease (AD) are the result of neuron and neuronal process losses due to a wide range of factors. To date, all efforts to develop therapies that target specific AD-related pathways have failed in late-stage human trials. As a result, an emerging consensus in the field is that treatment of AD patients with currently available drug candidates might come too late, likely as a result of significant neuronal loss in the brain. In this regard, cell-replacement therapies, such as human embryonic stem cell- or induced pluripotent stem cell-derived neural cells, hold potential for treating AD patients. With the advent of stem cell technologies and the ability to transform these cells into different types of central nervous system neurons and glial cells, some success in stem cell therapy has been reported in animal models of AD. However, many more steps remain before stem cell therapies will be clinically feasible for AD and related disorders in humans. In this review, we will discuss current research advances in AD pathogenesis and stem cell technologies; additionally, the potential challenges and strategies for using cell-based therapies for AD and related disorders will be discussed.     

Polymeric conjugates for drug delivery

The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both "see and treat" patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status.     

Recent progress in thermally activated delayed fluorescence dendrimers for solution-processed organic light-emitting diodes

During the past decade, the discovery of thermally activated delayed fluorescence (TADF) materials has significantly boosted the development of organic light-emitting diode (OLED) technology. Compared with small-molecule and polymeric TADF materials, TADF dendrimers have emerged as promising emitters for solution-processed OLEDs because they have the integrated advantages of TADF small molecules and polymers in achieving high efficiency, excellent solution processability, and precise molecular structures. In recent years, TADF dendrimers have experienced important advances in molecular design, mechanism exploration and device performance. Herein, we present a comprehensive review of solution-processable TADF dendrimers, mainly focusing on their molecular design principles and structure–property correlations. The advanced device performances of these dendrimers are also summarized. Finally, we proposed the prospects and challenges on the development of TADF dendrimers.     

A perspective on bioconjugated nanoparticles and quantum dots

Bioconjugated nanoparticles and quantum dots are among the most exciting nanomaterials with promising application potentials in nanomedicine field. These applications include biosensing, bioimaging, bioassay, targeted drug delivery and new therapeutic agents or method development. Although most of these applications are based on the optical properties of nanoparticle materials such as surface plasmon resonance, surface enhanced Raman scattering and strong photoluminescence, other aspects of nanoparticles such as the catalytic effect and amplification effect associated with the nanoscale dimension have also been explored. This review presents a narrative summary on the use of bioconjugated nanoparticles and quantum dots for biological applications, along with a discussion on some critical challenges existing in the field and possible solutions that have been or are being developed to overcome these challenges.     

Dendrimer as a versatile platform for biomedical application: A review

Modern chemistry is vastly fascinated by dendrimer chemistry, an area that is rapidly expanding and brimming with potential applications. Dendrimers are highly branched polymers that have multiple peripheral groups, interior cavities and they have many structural properties therefore Dendrimers play a crucial role in the fields of nanotechnology, pharmaceuticals, and medicinal chemistry. The terminal functional groups of dendrimers may be chemically linked to other moieties in order to adjust surface properties for applications such as biomimetic nanodevices. A variety of biologically active agents can be incorporated into dendrimers to create biologically active conjugates, including novel drug carriers, by utilizing the homogeneity of their three-dimensional architecture. The purpose of this review is to provide a brief overview of bio-inspired dendrimer applications, highlighting their use as drug and gene delivery agents, and biomedical diagnostic agents. In addition, the review mentions briefly some dendrimer applications in cosmetics, agrochemicals, and catalyst.     

Dendrimers in drug research

Dendrimers are versatile, derivatisable, well-defined, compartmentalised chemical polymers with sizes and physicochemical properties resembling those of biomolecules e.g. proteins. The present critical review (citing 158 references) briefly describes dendrimer design, nomenclature and divergent/convergent dendrimer synthesis. The characteristic physicochemical features of dendrimers are highlighted, showing the effect of solvent pH and polarity on their spatial structure. The use of dendrimers in biological systems are reviewed, with emphasis on the biocompatibility of dendrimers, such as in vitro and in vivo cytotoxicity, as well as biopermeability, biostability and immunogenicity. The review deals with numerous applications of dendrimers as tools for efficient multivalent presentation of biological ligands in biospecific recognition, inhibition and targeting. Dendrimers may be used as drugs for antibacterial and antiviral treatment and have found use as antitumor agents. The review highlights the use of dendrimers as drug or gene delivery devices in e.g. anticancer therapy, and the design of different host-guest binding motifs directed towards medical applications is described. Other specific examples are the use of dendrimers as 'glycocarriers' for the controlled multimeric presentation of biologically relevant carbohydrate moieties which are useful for targeting modified tissue in malignant diseases for diagnostic and therapeutic purposes. Finally, the use of specific types of dendrimers as scaffolds for presenting vaccine antigens, especially peptides, for use in vaccines is presented.     

液相色谱-质谱在阿尔茨海默病研究中的应用

液相色谱-质谱联用（LC-MS）作为集高效分离与定性定量检测为一体的联用技术,近年来在化学、医学、药学和生物化学等领域获得了长足的发展,特别是由科研领域拓展到临床诊断,开启了疾病诊断技术的新篇章。阿尔茨海默病（Alzheimer’s disease,AD）,又称老年性痴呆症,是现代社会第四大致死疾病。随着我国人口的快速老龄化,重视对AD的防治是实现健康老龄化以及国民经济持续发展的重要保障之一。本文对LC-MS的新进展进行了简介,并详细综述了近3年来其在AD研究中的应用,以期相关方法获得更好的理解与更多的关注。     

Controlled Drug Delivery Systems: Current Status and Future Directions

The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional drug delivery systems (tablets, capsules, syrups, ointments, etc.) suffer from poor bioavailability and fluctuations in plasma drug level and are unable to achieve sustained release. Without an efficient delivery mechanism, the whole therapeutic process can be rendered useless. Moreover, the drug has to be delivered at a specified controlled rate and at the target site as precisely as possible to achieve maximum efficacy and safety. Controlled drug delivery systems are developed to combat the problems associated with conventional drug delivery. There has been a tremendous evolution in controlled drug delivery systems from the past two decades ranging from macro scale and nano scale to intelligent targeted delivery. The initial part of this review provides a basic understanding of drug delivery systems with an emphasis on the pharmacokinetics of the drug. It also discusses the conventional drug delivery systems and their limitations. Further, controlled drug delivery systems are discussed in detail with the design considerations, classifications and drawings. In addition, nano-drug delivery, targeted and smart drug delivery using stimuli-responsive and intelligent biomaterials is discussed with recent key findings. The paper concludes with the challenges faced and future directions in controlled drug delivery.