Biomedical application of responsive ‘smart’ electrospun nanofibers in drug delivery system: A minireview

Electrospinning is a versatile method for producing continuous nanofibers. It has since become an easy and cost-effective technique in the manufacturing process and drawn keen interests in most biomedical field applications. Nanofibers have garnered great attention in nanomedicine due to their resemblance with the extracellular matrix (ECM). Like nanoparticles, its unique characteristics of higher surface-to-volume ratio and the tunability of the polymers utilizing nanofiber have increased the efficiency in encapsulation and drug-loading capabilities. Smart or “stimuli-responsive” polymers have shown particular fascination in controlled release, where their ability to react to minor changes in the environment, such as temperature, pH, electric field, light, or magnetic field, distinguishes them as intelligent. Polymers are a popular material for the design of drug delivery carriers; consequently, various types of drugs, including antiviral, proteins, antibiotics, DNA and RNA, are successfully encapsulated in the pH-dependent nanofibers with smart polymers which is a polymer that can respond to change such as pH change, temperature. In this minireview, we discuss applications of smart electrospun pH-responsive nanofibers in the emerging biomedical developments which includes cancer drug targeting, oral controlled release, wound healing and vaginal drug delivery.     

Stimuli-responsive hydrogels based on polysaccharides incorporated with thermo-responsive polymers as novel biomaterials

In recent years, intelligent hydrogels which can change their swelling behavior and other properties in response to environmental stimuli such as temperature, pH, solvent composition and electric fields, have attracted great interest. The hydrogels based on polysaccharides incorporated with thermo-responsive polymers have shown unique properties such as biocompatibility, biodegradability, and biological functions in addition to the stimuli-responsive characters. These "smart" hydrogels exhibit single or multiple stimuli-responsive characters which could be used in biomedical applications, including controlled drug delivery, bioengineering or tissue engineering. This review focuses on the recent developments and future trends dealing with stimuli-responsive hydrogels based on grafting/blending of polysaccharides such as chitosan, alginate, cellulose, dextran and their derivatives with thermo-sensitive polymers. This review also screens the current applications of these hydrogels in the fields of drug delivery, tissue engineering and wound healing.     

Remotely controlled electro-responsive on-demand nanotherapy based on amine-modified graphene oxide for synergistic dual drug delivery

This study focuses on the development of a new electric field responsive graphene oxide (GO) nanoparticle system for on-demand drug delivery. Today, GO is an attractive option adopted in various biological applications for its exclusive features such as flexibility, conductiveness, cost-effectiveness, and external stimuli-responsive nature. It is usual to utilize multiple drugs in cancer treatment. This kind of therapy has lesser side-effects, drug resistance, and is more effective than utilizing only one drug. This study aims to determine low-voltage-controlled dual drug (aspirin and doxorubicin) release from GO surface. Here, we have demonstrated how to control the drug release rate remotely with a handy mobile phone, with zero passive release at idle time. In addition, the study focused to estimate the synergism of aspirin with doxorubicin in the release mechanism from GO in the presence of external voltage, using the spectroscopic method. Moreover, we observed aspirin- and doxorubicin-induced synergistic antitumor activity in MDA-MB 231 (breast cancer cell) in vitro. Thus, our study presents a noble combination of aspirin and doxorubicin that could be utilized for remotely controlled on-demand drug delivery for triple negative breast cancer treatment, using GO as a carrier.     

Advances in Intelligent Stimuli-Responsive Microneedle for Biomedical Applications

Microneedles (MNs) are a new type of drug delivery method that can be regarded as an alternative to traditional transdermal drug delivery systems. Recently, MNs have attracted widespread attention for their advantages of effectiveness, safety, and painlessness. However, the functionality of traditional MNs is too monotonous and limits their application. To improve the efficiency of disease treatment and diagnosis by combining the advantages of MNs, the concept of intelligent stimulus-responsive MNs is proposed. Intelligent stimuli-responsive MNs can exhibit unique biomedical functions according to the internal and external environment changes. This review discusses the classification and principles of intelligent stimuli-responsive MNs, such as magnet, temperature, light, electricity, reactive oxygen species, pH, glucose, and protein. This review also highlights examples of intelligent stimuli-responsive MNs for biomedical applications, such as on-demand drug delivery, tissue repair, bioimaging, detection and monitoring, and photothermal therapy. These intelligent stimuli-responsive MNs offer the advantages of high biocompatibility, targeted therapy, selective detection, and precision treatment. Finally, the prospects and challenges for the application of intelligent stimuli-responsive MNs are discussed.     

Recent progress in applications of graphene oxide for gas sensing: A review

This paper is a review of the recent progress on gas sensors using graphene oxide (GO). GO is not a new material but its unique features have recently been of interest for gas sensing applications, and not just as an intermediate for reduced graphene oxide (RGO). Graphene and RGO have been well known gas-sensing materials, but GO is also an attractive sensing material that has been well studied these last few years. The functional groups on GO nanosheets play important roles in adsorbing gas molecules, and the electric or optical properties of GO materials change with exposure to certain gases. Addition of metal nanoparticles and metal oxide nanocomposites is an effective way to make GO materials selective and sensitive to analyte gases. In this paper, several applications of GO based sensors are summarized for detection of water vapor, NO₂, H₂, NH₃, H₂S, and organic vapors. Also binding energies of gas molecules onto graphene and the oxygenous functional groups are summarized, and problems and possible solutions are discussed for the GO-based gas sensors.     

Graphene-based sensors for detection of heavy metals in water: a review

Graphene (G) is attracting significant attention because of its unique physical and electronic properties. The production of graphene through the reduction of graphene oxide (GO) is a low-cost method. The reduction of GO can further lead to electrically conductive reduced GO. These graphene-based nanomaterials are attractive for high-performance water sensors due to their unique properties, such as high specific surface areas, high electron mobilities, and exceptionally low electronic noise. Because of potential risks to the environment and human health arising from heavy-metal pollution in water, G-/GO-based water sensors are being developed for rapid and sensitive detection of heavy-metal ions. In this review, a general introduction to graphene and GO properties, as well as their syntheses, is provided. Recent advances in optical, electrochemical, and electrical detection of heavy-metal ions using graphene or GO are then highlighted. Finally, challenges facing G/GO-based water sensor development and outlook for future research are discussed.     

A Review on Graphene Oxide Two-dimensional Macromolecules: from Single Molecules to Macro-assembly

Graphene oxide(GO), which consists of two-dimensional(2 D) sp² carbon hexagonal networks and oxygen-contained functional groups, has laid the foundation of mass production and applications of graphene materials. Made by chemical oxidation of graphite, GO is highly dispersible or even solubilized in water and polar organic solvents, which resolves the hard problem of graphene processing and opens a door to wet-processing of graphene. Despite its defects, GO is easy to functionalize, dope, punch holes, cut into pieces, conduct chemical reduction, form lyotropic liquid crystal, and assemble into macroscopic materials with tunable structures and properties as a living building block. GO sheet has been viewed as a single molecule, a particle, as well as a soft polymer material. An overview on GO as a 2 D macromolecule is essential for studying its intrinsic properties and guiding the development of relevant subjects. This review mainly focuses on recent advances of GO sheets, from single macromolecular behavior to macro-assembled graphene material properties. The first part of this review offers a brief introduction to the synthesis of GO molecules. Then the chemical structure and physical properties of GO are presented, as well as its polarity in solvent and rheology behavior. Several key parameters governing the ultimate stability of GO colloidal behavior, including size, p H and the presence of cation in aqueous dispersions, are highlighted. Furthermore, the discovery of GO liquid crystal and functionalization of GO molecules have built solid new foundations of preparing highly ordered, architecture-tunable, macro-assembled graphene materials, including 1 D graphene fibers, 2 D graphene films, and 3 D graphene architectures. The GO-based composites are also viewed and the interactions between these target materials and GO are carefully discussed. Finally, an outlook is provided in this field, where GO is regarded as macromolecules, pointing out the challenges and opportunities that exist in the field. We hope that this review will be beneficial to the understanding of GO in terms of chemical structure,molecular properties, macro-assembly and potential applications, and encourage further development to extend its investigations from basic research to practical applications.     

Functional Microneedle Patch for Wound Healing and Biological Diagnosis and Treatment

Wound healing, especially chronic wounds, has been one of the major challenges in the field of biomedicine. Drug therapy alone is not effective, so a variety of functional wound healing dressings have been developed. Microneedles have attracted more and more attentions in the field of wound healing dressings due to their penetration and high drug delivery efficiency. In this review, all the studies on the application of microneedles in wound healing in recent years are summarized, classify different microneedles according to their functions in the process of wound healing, discuss the current challenges in the transformation of microneedle technology toward clinical applications, and finally look forward to the future design and development directions of microneedles in this field.     

Pillararene-Based Supramolecular Vesicles for Stimuli-Responsive Drug Delivery

Supramolecular vesicles (SMVs) self-assembled from the supra-amphiphiles, consisting of two scaffolds linked together through noncovalent interactions, can realize stimuli-responsive controlled release of encapsulated drugs for enhanced therapeutic efficacy and minimized side effect of drugs. Pillararenes (PAs), an emerging kind of macrocyclic hosts in 2008, are easy to modify with a variety of functionalities. SMVs from PAs and specific guests mainly based on the host–guest interactions have attracted increasing attention because of their drug delivery and controlled drug release. A great progress in the construction and stimuli-responsive drug delivery of the PA-based SMVs has been made since the first work was reported in 2012. This review summarizes the major achievements of the PA-based SMVs for stimuli-responsive drug delivery over the past 5 years, including the microstructures of SMVs, multiple stimuli-responsive SMVs, prodrug SMVs from prodrug PAs and guests, bola-type SMVs, multifunctional SMVs, glucose-responsive SMVs for insulin delivery, novel SMVs from responsive PAs, thermo-responsive SMVs, and ternary SMVs, for chemotherapy, photothermal therapy, photodynamic therapy, and other biological applications. The future challenges and research directions of PA-based SMVs are also outlined from the points of views of the fundamental research, biological applications, and clinical applications of PA-based SMVs.     

Stimuli-responsive microemulsions: State-of-the-art and future prospects

Over the last decade, stimuli-responsive microemulsions, that is, those that switch between stable and unstable states in response to certain stimuli, have attracted considerable attention because of their unique properties and potential for diverse applications. Herein, we highlight the recent advances in the development of microemulsions responsive to external triggers such as pH, redox reactions, light, CO₂ gas, magnetic field and temperature; discuss the corresponding responses; and reveal important composition–microstructure–macroscopic property relationships to suggest future research directions and potential applications.     

Supramolecular polymers constructed by crown ether-based molecular recognition

Supramolecular polymers, polymeric systems beyond the molecule, have attracted more and more attention from scientists due to their applications in various fields, including stimuli-responsive materials, healable materials, and drug delivery. Due to their good selectivity and convenient enviro-responsiveness, crown ether-based molecular recognition motifs have been actively employed to fabricate supramolecular polymers with interesting properties and novel applications in recent years. In this tutorial review, we classify supramolecular polymers based on their differences in topology and cover recent advances in the marriage between crown ether-based molecular recognition and polymer science.     

Functionalized mesoporous silica materials for controlled drug delivery

In the past decade, non-invasive and biocompatible mesoporous silica materials as efficient drug delivery systems have attracted special attention. Great progress in structure control and functionalization (magnetism and luminescence) design has been achieved for biotechnological and biomedical applications. This review highlights the most recent research progress on silica-based controlled drug delivery systems, including: (i) pure mesoporous silica sustained-release systems, (ii) magnetism and/or luminescence functionalized mesoporous silica systems which integrate targeting and tracking abilities of drug molecules, and (iii) stimuli-responsive controlled release systems which are able to respond to environmental changes, such as pH, redox potential, temperature, photoirradiation, and biomolecules. Although encouraging and potential developments have been achieved, design and mass production of novel multifunctional carriers, some practical biological application, such as biodistribution, the acute and chronic toxicities, long-term stability, circulation properties and targeting efficacy in vivo are still challenging.     

Stimulus-responsive polymeric nanoparticles for biomedical applications

Polymeric nanoparticles with unique properties are regarded as the most promising materials for biomedical applications including drug delivery and in vitro/in vivo imaging.Among them,stimulus-responsive polymeric nanoparticles,usually termed as intelligent nanoparticles,could undergo structure,shape,and property changes after being exposed to external signals including pH,temperature,magnetic field,and light,which could be used to modulate the macroscopical behavior of the nanoparticles.This paper reviews ...     

刺激响应纳米碳杂化材料

碳纳米管和石墨烯是碳纳米材料的典型代表,其纳米尺度赋予了其优异的光、电、热以及机械性能。然而,这些碳纳米材料间存在较强的范德华力,导致其溶解性差,后续加工处理困难。为提高碳纳米材料的溶解性,通常利用聚合物或其它小分子物质对其进行修饰。而利用刺激响应性聚合物或化合物功能化碳纳米材料,不仅可以提高其溶解性,还可以赋予其环境刺激响应功能。本文主要综述了近年来利用温度、pH、光以及CO2响应聚合物或小分子化合物对碳纳米管和石墨烯进行共价键、非共价键修饰并赋予其环境刺激响应特性的方法、功能和相关应用,展望了修饰得到的纳米碳杂化材料的应用前景及下一步发展方向。     

Smart polymer grafted silica based drug delivery systems

Smart polymers are a special class of polymers, which respond to the various external stimuli by changing their properties. Recent developments in synthetic polymer chemistry have provided the possibility of designing and synthesis of various new stimuli-responsive polymers. These stimuli-responsive polymers can be used to prepare smart drug delivery systems (DDS) by grafting them on various nanomaterials. The main aim of this review is to present collective information on various stimuli-responsive polymers grafted on silica nanoparticles for the preparation of smart DDS. The stimuli covered are pH, temperature, redox, reactive oxygen species (ROS), glucose concentration, enzymes, magnetic field, and so forth. The structures of various stimuli-responsive polymers are shown with their relevance to the preparation of smart DDS. The crucial roles of macromolecular design and synthesis of smart polymers in the development of stimuli-responsive DDS are discussed with examples from literature and the challenges that still exist in this area of research are presented.     

Alternating Magnetic Field Controlled Targeted Drug Delivery Based on Graphene Oxide-Grafted Nanosupramolecules

Graphene oxide (GO)-grafted nanosupramolecules have recently emerged as neoteric nano drug carriers in the therapy of refractory diseases. Herein, a multicomponent nanosupramolecular drug carrier based on a targeted peptide and magnetic GO is reported, the drug-release behavior of which can be regulated by an alternating magnetic field (AMF). This multicomponent nanosupramolecular carrier is composed of β-cyclodextrin (β-CD)/nickel nanoparticle-modified graphene oxide (GONiCD) and mitochondrial ion-targeting peptide (MitP)-grafted hyaluronic acid (HAMitP). Owing to the host–guest interaction between β-cyclodextrin and the cyclohexyl groups on MitP, GONiCD and HAMitP could form supramolecular assemblies during the doxorubicin (Dox) loading process, which not only remarkably enhances the drug-loading capacity, but also improves the drug-release efficiency under AMF stimulus. During co-incubation with tumor cells, the Dox-loaded assemblies could strongly target the tumor mitochondria and damage both the mitochondria and the nuclei, owing to Dox release from the assemblies induced by AMF. This study sheds light on the exploration of peptide caps for controlled drug loading/release of supramolecular nanocarriers for efficient drug delivery and anticancer therapy.     

Mechanically Strong Janus Poly(N-isopropylacrylamide)/Graphene Oxide Hydrogels as Thermo-responsive Soft Robots

Simple preparation of stimuli-responsive hydrogels with good mechanical properties and mild stimuliresponsiveness is essential for their applications as smart soft robots.Mechanically strong Janus poly(Nisopropylacrylamide)/graphene oxide (PNIPAM/GO) nanocomposite hydrogels with stimuli-responsive bending behaviors are prepared through a simple one-step method by using molds made of a Teflon plate and a glass plate.Residual oxygen in the air bubbles on the Teflon plate surface affects the polymerization and hence the cross-linking density,leading to the different swelling/deswelling rates of the two sides of the gels.Therefore,the hydrogels exhibit bending/unbending behaviors upon heating/cooling in water.The incorporation of GO nanosheets dramatically enhances the mechanical properties of Janus hydrogels.Meanwhile,the photo-responsive property of the GO nanosheets also imparts the hydrogels with remotecontrollable deformation under IR irradiation.The application of the Janus PNIPAM/GO hydrogels as thermo-responsive grippers is demonstrated.     

Hyaluronic Acid-Conjugated Carbon Nanomaterials for Enhanced Tumour Targeting Ability

Hyaluronic acid (HA) has been implemented for chemo and photothermal therapy to target tumour cells overexpressing the CD44⁺ receptor. HA-targeting hybrid systems allows carbon nanomaterial (CNM) carriers to efficiently deliver anticancer drugs, such as doxorubicin and gemcitabine, to the tumour sites. Carbon nanotubes (CNTs), graphene, graphene oxide (GO), and graphene quantum dots (GQDs) are grouped for a detailed review of the novel nanocomposites for cancer therapy. Some CNMs proved to be more successful than others in terms of stability and effectiveness at removing relative tumour volume. While the literature has been focused primarily on the CNTs and GO, other CNMs such as carbon nano-onions (CNOs) proved quite promising for targeted drug delivery using HA. Near-infrared laser photoablation is also reviewed as a primary method of cancer therapy—it can be used alone or in conjunction with chemotherapy to achieve promising chemo-photothermal therapy protocols. This review aims to give a background into HA and why it is a successful cancer-targeting component of current CNM-based drug delivery systems.     

刺激响应型生物医用聚合物纳米粒子研究进展

近十几年来, 纳米科学的发展极大地推动了纳米材料在生物医用领域的应用. 聚合物纳米粒子由于其独特的性能在药物传递、医学成像等医用领域备受关注. 其中, 刺激响应型聚合物纳米粒子是一类可以在外界信号刺激下(包括pH、温度、磁场、光等)发生结构、形状、性能改变的纳米粒子. 利用这种刺激响应性可调节纳米粒子的某种宏观行为, 故而刺激响应型聚合物纳米粒子也被称为智能纳米粒子. 因为其特有的“智能性”, 刺激响应型聚合物纳米粒子的研究已成为当前生物材料领域的研究热点. 本文综述了几类重要的生物医用刺激响应型聚合物纳米粒子, 侧重介绍双重及多重刺激响应型聚合物纳米粒子的制备及其生物医学应用.     

Advances in Targeting Drug Biological Carriers for Enhancing Tumor Therapy Efficacy

Chemotherapy drugs continue to be the main component of oncology treatment research and have been proven to be the main treatment modality in tumor therapy. However, the poor delivery efficiency of cancer therapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. The recent integration of biological carriers and functional agents is expected to camouflage synthetic biomimetic nanoparticles for targeted delivery. The promising candidates, including but not limited to red blood cells and their membranes, platelets, tumor cell membrane, bacteria, immune cell membrane, and hybrid membrane are typical representatives of biological carriers because of their excellent biocompatibility and biodegradability. Biological carriers are widely used to deliver chemotherapy drugs to improve the effectiveness of drug delivery and therapeutic efficacy in vivo, and tremendous progress is made in this field. This review summarizes recent developments in biological vectors as targeted drug delivery systems based on microenvironmental stimuli-responsive release, thus highlighting the potential applications of target drug biological carriers. The review also discusses the possibility of clinical translation, as well as the exploitation trend of these target drug biological carriers.