Oligopeptide Self-Assembly:Mechanisms,Stimuli-Responsiveness,and Biomedical Applications

Oligopeptide self-assembly materials have emerged as a promising class of biomaterials with diverse applications in biomedicine.This review highlights the recent progress in comprehending the selfassembly mechanisms intrinsic to oligopeptides and their behavior in response to specific stimuli.By methodically structuring the amino acid sequence and managing external stimuli such as pH levels,redox conditions,or enzymatic activity,we can exercise unprecedented control over the self-assembly process.By controlling the self-assembly process of oligopeptides,various structures with extraordinary versatility can be obtained,including micelles,nanofibers,and coacervate droplets,each possessing modifiable mechanical and chemical properties.Furthermore,these self-assembled constructs demonstrate immense potential within varied biomedical applications.The stimuli-sensitive nature of oligopeptide assembly materials facilitates timely encapsulation and release of therapeutic cargos,consequently eliciting desired cellular responses.This approach paves the way for more precise tumor targeting,personalized medicinal treatments,and well-regulated drug dispensation.Their innate biocompatibility and proficiency in replicating the extracellular matrix(ECM)render them ideally suited for applications such as tissue engineering,wound remediation,and regenerative medicine.In summary,oligopeptide self-assembling materials show tremendous potential as adaptable platforms for cutting-edge biomedical applications,thereby bridging the divide between fundamental research and practical clinical application.

Facile Synthesis of Cellulose Acetate Ultrafiltration Membrane with Stimuli-Responsiveness to pH and Temperature Using the Additive of F127-b-PDMAEMA

We fabricate a novel cellulose acetate （CA） ultrafiltration membrane modified by block copolymer F127-b- PDMAEMA, which is synthesized using F127 and DMAEMA via the ARGET ATRP method. Compared to conven- tional ultrafiltration membranes, the incorporation of both F 127 and PDMAEMA can not only readily increase the hydrophilicity of the membrane, but also exhibit stimuli-responsiveness to temperature and pH. Fourier transform infrared spectroscopy （FT-IR）, nuclear magnetic resonance spectroscopy （NMR）, and gel permeation chromatog- raphy （GPC） are employed to analyze the structure of the F 127-b-PDMAEMA. The membrane properties are eval- uated via scanning electron microscope （SEM） imaging, porosity test, automatic target recognition Fourier trans- form infrared spectroscopy （ATR-FTIR）, water contact angle test and permeation test. The results indicate that the F 127-b-PDMAEMA is an excellent pore agent, which contributes to an enhancement of the membrane in sensitivity to temperature and pH. The modified membrane also exhibits lower water contact angle （64.5~）, which is attributed to the good anti-fouling performance and high water permeation.

Recent progress in stimuli-responsive DNA-based logic gates:Design,working principles and biological applications

Stimuli-responsive DNA-based logic gates have emerged as a promising field at the intersection of synthetic biology and nanotechnology.These gates exploit the unique properties of DNA molecules to perform programmable computational operations in response to specific stimuli.This review provides a comprehensive overview of recent advancements in the design,working principles,and applications of stimuli-responsive DNA-based logic gates.The progress made in developing various types of logic gates triggered by metal ions,pH,oligonucleotides,small molecules,proteins,and light is highlighted.The applications of these logic gates in imaging and biosensing,drug delivery,synthetic biology and molecular computing are discussed.This review underscores the significant contributions and future prospects of stimuli-responsive DNA-based logic gates in advancing the field of nanotechnology.

Stimuli-responsive nanocarriers for therapeutic applications in cancer

Cancer has become a very serious challenge with aging of the human population.Advances in nanotechnology have provided new perspectives in the treatment of cancer.Through the combination of nanotechnology and therapeutics,nanomedicine has been successfully used to treat cancer in recent years.In terms of nanomedicine,nanocarriers play a key role in delivering therapeutic agents,reducing severe side effects,simplifying the administration scheme,and improving therapeutic efficacies.Modulations of the structure and function of nanocarriers for improved therapeutic efficacy in cancer have attracted increasing attention in recent years.Stimuli-responsive nanocarriers penetrate deeply into tissues and respond to external or internal stimuli by releasing the therapeutic agent for cancer therapy.Notably,stimuli-responsive nanocarriers reduce the severe side effects of therapeutic agents,when compared with systemic chemotherapy,and achieve controlled drug release at tumor sites.Therefore,the development of stimuli-responsive nanocarriers plays a crucial role in drug delivery for cancer therapy.This article focuses on the development of nanomaterials with stimuli-responsive properties for use as nanocarriers,in the last few decades.These nanocarriers are more effective at delivering the therapeutic agent under the control of external or internal stimuli.Furthermore,nanocarriers with theranostic features have been designed and fabricated to confirm their great potential in achieving effective treatment of cancer,which will provide us with better choices for cancer therapy.

Stimuli-Responsive Gene Delivery Nanocarriers for Cancer Therapy

Gene therapy provides a promising approach in treating cancers with high efficacy and selectivity and few adverse effects.Currently,the development of functional vectors with safety and effectiveness is the intense focus for improving the delivery of nucleic acid drugs for gene therapy.For this purpose,stimuli-responsive nanocarriers displayed strong potential in improving the overall efficiencies of gene therapy and reducing adverse effects via effective protection,prolonged blood circulation,specific tumor accumulation,and controlled release profile of nucleic acid drugs.Besides,synergistic therapy could be achieved when combined with other therapeutic regimens.This review summarizes recent advances in various stimuliresponsive nanocarriers for gene delivery.Particularly,the nanocarriers responding to endogenous stimuli including pH,reactive oxygen species,glutathione,and enzyme,etc.,and exogenous stimuli including light,thermo,ultrasound,magnetic field,etc.,are introduced.Finally,the future challenges and prospects of stimuli-responsive gene delivery nanocarriers toward potential clinical translation are well discussed.The major objective of this review is to present the biomedical potential of stimuli-responsive gene delivery nanocarriers for cancer therapy and provide guidance for developing novel nanoplatforms that are clinically applicable.

Stimuli-responsive emulsions:Recent advances and potential applications

Responsive emulsions are the emulsions that can be reversibly switched on-demand between“stable”and“unstable”by environmental stimulus or trigger,which allows a simple and effective adjustment approach to achieve emulsification and demulsification.In recent years,stimuli-responsive emulsions acting as smart soft material are received considerable attention with the advantages of simple manipulation,good reversibility,low cost,easy treatment,and little effect on the system.In this paper,the recent research progress of emulsions that can respond to external stimuli,including pH,light,magnetic field,CO_(2)/N_(2) and dual responsive are reviewed.Also,the potential applications based on responsive emulsion are discussed,such as catalytic reactions,heavy oil recovery,polymer particles synthesis and optical sensor,aiming to summarize the latest achievements and put forward the possible development trends of responsive emulsions.

Recent Advances of D-α-tocopherol Polyethylene Glycol 1000 Succinate Based Stimuli-responsive Nanomedicine for Cancer Treatment

D-a-tocopherol polyethylene glycol 1000 succinate(TPGS)is a pharmaceutical excipient approved by Chinese NMPA and FDA of USA.It's widely applied as a multifunctional drug carrier for nanomedicine.The advantages of TPGS include P-glycoprotein(P-gp)inhibition,penetration promotion,apoptosis induction via mitochondrial-associated apoptotic pathways,multidrug resistant(MDR)reversion,metastasis inhibition and so on.TPGS-based drug delivery systems which are responding to extermal stimulus can combine the inhibitory functions of TPGS towards P-gp with the environmentally responsive controlled release property and thus exerts a synergistic anti-cancer effect,through increased intracellular drug concentration in tumors cells and well-controlled drug release behavior.In this review,TPGS-based nano-sized delivery systems responsive to different stimuli were summarized and discussed,including pH-responsive,redox-responsive and multi-responsive systems in various formulations.The achievements,mechanisms and diffcrent characteristics of TPGS-bascd stimuli-responsive drug-delivery systems in tumor therapy were also outlined.

Click-Formed Polymer Gels with Aggregation-Induced Emission and Dual Stimuli-Responsive Behaviors

Stimuli-responsive polymer gels have recently attracted great attention due to their heat/solvent resistance,dimensional stability,and unique sensitivity to external stimuli.In this work,we synthesized thiol-functionalized tetraphenylethylene(TPE)and constructed polymer gels through thiol-ene click reaction.The synthetic process of the polymer gels could be monitored by fluorescence emission of TPE moieties based on aggregation-induced emission mechanism.In addition,due to the dual redox-and acid responsiveness of the polymer gels,in the presence of dithiothreitol and trifluoroacetic acid,fluorescence quenching of the polymer gels can be observed.This stimuli-responsive characteristics endows the polymer gels with potential applications in fluorescent sensing and imaging,cancer diagnosis and selfhealing materials.

Dynamic DNA nanomachines for amplification imaging of diseased cells based on stimuli-responsive mechanism

As a basic functional unit,living cell with sophisticated structures play an indispensable role in life activities.Since the abnormality of important molecules inside cells is closely related to diseases,the dynamic analysis and spatio-temporal monitoring of specific molecules in living cells can provide precious information for the diagnosis and treatment of diseases.More recently,DNA has not only been recognized as the carrier of genetic information,but has also used as a robust building block for the assembly of multitudinous nanoscale structures due to the intrinsic advantages of high programmability of classic Watson–Crick base-pairing rule.Intensive study promotes the rapid progress of nanotechnology in various fields,such as bioimaging,diagnosis,and therapeutics.Among numerous well-defined DNA nanomaterials,DNA nanomachines have been widely exploited in cell imaging owing to their desirable ability to achieve high-resolution temporal and spatial images in response to endogenous or exogenous stimuli.In brief,elaborate DNA nanomachines can undergo structural changes upon the stimuli of target analytes or environmental factors,resulting in rapid increase or reduction of output signals and thereby indirectly reflecting the expression level of targets.DNA nanomachines with high sensitivity and specificity contribute to the recognition of diseased tissues.In this review,we introduce the basic assembly modules of DNA nanomachines and summarize the recent advances in dynamic DNA nanomachines for diseased-cell imaging.Finally,the current challenges and future directions of DNA nanomachines for bioimaging are discussed.

Smart anticorrosion coating based on stimuli-responsive micro/nanocontainer:a review

Smart coating for corrosion protection of metal materials(steel,magnesium,aluminum and their alloys)has drawn great attention because of their capacity to prevent crack propagation in the protective coating by releasing functional molecules(healing agents or corrosion inhibitors)on demand from delivery vehicle,that is,micro/nanocontainer made up of a shell and core material or a coating layer,in a controllable manner.Herein,we summarize the recent achievements during the last 10 years in the field of the micro/nanocontainer with different types of stimuli-responsive properties,i.e.,pH,electrochemical potential,redox,aggressive corrosive ions,heat,light,magnetic field,and mechanical impact,for smart anticorrosion coating.The state-of-the-art design and fabrication of micro/nanocontainer are emphasized with detailed examples.

Smart stimuli-responsive drug delivery systems in spotlight of COVID-19

The world has been dealing with a novel severe acute respiratory syndrome(SARS-CoV-2)since the end of 2019,which threatens the lives of many peopleworldwide.COVID-19 causes respiratory infection with different symptoms,from sneezing and coughing to pneumonia and sometimes gastric symptoms.Researchers worldwide are actively developing novel drug delivery systems(DDSs),such as stimuli-responsive DDSs.The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating“smart”DDS that can effectively control dosage,sustained release,individual variations,and targeted delivery.To conduct a comprehensive literature survey for this article,the terms“Stimuli-responsive”,“COVID-19”and“Drug delivery”were searched on databases/search engines like“Google Scholar”,“NCBI”,“PubMed”,and“Science Direct”.Many different types of DDSs have been proposed,including those responsive to various exogenous(light,heat,ultrasound andmagnetic field)or endogenous(microenvironmental changes in pH,ROS and enzymes)stimuli.Despite significant progress in DDS research,several challenging issues must be addressed to fill the gaps in the literature.Therefore,this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.

Recent advances in endogenous and exogenous stimuli-responsive nanoplatforms for bacterial infection treatment

As drug-resistant bacterial infections escalate and antimicrobial resources become insufficient,new alternative therapies are critical.The emergence of nano drug delivery system,in addition to giving drugs sustained,targeted or longer half-life characteristics,also plays an important role in improving the therapeutic effect and reducing the toxic side effects of conventional drugs.Despite its potential benefits,the traditional nanomedical drug delivery system has some practical limitations,including incomplete and slow drug release,as well as insufficient accumulation at infection sites.Stimuli responsive nanoplatforms are hence developed to overcome the disadvantages of conventional nanoparticles,which can provide several advantages like:enhancing the pharmacokinetics and biodistribution of antimicrobial drugs,increasing their effective bioavailability,reducing their dosage frequency,and improving their antimicrobial efficacy against biofilm-related infections,while slowing down the development of antimicrobial resistance,which is expected to trigger a medical revolution in the field of human health,thus bringing huge clinical benefits.In this review,we provide an extensive review of the recent progress of endogenous and exogenous stimuli-responsive nanoplatforms in the antibacterial area.Using specific infectious microenvironments(pH,enzymes,reactive oxygen species and toxins),this review systematically presents the design principles of nano delivery systems and the mechanisms by which endogenous stimuli induce changes in the morphology or properties of delivery systems to achieve programmed drug release.Furthermore,exogenous stimuli such as light,heat,and magnetic fields can also control the release of drugs.Last but not least,we discussed the challenges and opportunities for future clinical translation of stimuli-responsive nanoplatforms in bacterial infections.

Recent advances on thermosensitive hydrogels-mediated precision therapy

Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites,increased therapeutic efficacy,and reduced adverse effects.Over the past few years,sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential.These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature.Inspired by their unique properties,thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine.In this review,the state-of-theart developments in thermosensitive hydrogels for precision therapy are investigated,which covers from the thermo-gelling mechanisms and main components to biomedical applications,including wound healing,anti-tumor activity,osteogenesis,and periodontal,sinonasal and ophthalmic diseases.The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.

Stimuli-responsive microcarriers and their application in tissue repair: A review of magnetic and electroactive microcarrier

Microcarrier applications have made great advances in tissue engineering in recent years, which can load cells,drugs, and bioactive factors. These microcarriers can be minimally injected into the defect to help reconstruct agood microenvironment for tissue repair. In order to achieve more ideal performance and face more complextissue damage, an increasing amount of effort has been focused on microcarriers that can actively respond toexternal stimuli. These microcarriers have the functions of directional movement, targeted enrichment, materialrelease control, and providing signals conducive to tissue repair. Given the high controllability and designabilityof magnetic and electroactive microcarriers, the research progress of these microcarriers is highlighted in thisreview. Their structure, function and applications, potential tissue repair mechanisms, and challenges are discussed.In summary, through the design with clinical translation ability, meaningful and comprehensiveexperimental characterization, and in-depth study and application of tissue repair mechanisms, stimuliresponsivemicrocarriers have great potential in tissue repair.

ROS-responsive drug delivery systems for biomedical applications

In the field of biomedicine, stimuli-responsive drug delivery systems(DDSs) have become increasingly popular due to their site-specific release ability in response to a certain physiological stimulus, which may result in both enhanced treatment outcome and reduced side effects. Reactive oxygen species(ROS) are the unavoidable consequence of cell oxidative metabolism. ROS play a crucial part in regulating biological and physiological processes,whereas excessive intracellular ROS usually lead to the oxidation stress which has implications in several typical diseases such as cancer, inflammation and atherosclerosis. Therefore,ROS-responsive DDSs have elicited widespread popularity for their promising applications in a series of biomedical research because the payload is only released in targeted cells or tissues that overproduce ROS. According to the design of ROS-responsive DDSs, the main release mechanisms of therapeutic agents can be ascribed to ROS-induced carrier solubility change, ROS-induced carrier cleavage or ROS-induced prodrug linker cleavage. This review summarized the latest development and novel design of ROS-responsive DDSs and discussed their design concepts and the applications in the biomedical field.

Design, preparation and pharmacodynamics of ICG-Fe(Ⅲ) based HCPT nanocrystals against cancer

The use of nanocrystal technology to manufacture drug delivery systems intended to enhance therapeutic efficacy has attracted the attention of the pharmaceutical industry.However,the clinical application of nanocrystal drugs for injection is restricted by Ostwald ripening and the large-scale use of stabilizers such as polysorbate and lecithin,which have potential toxicity risks including hemolysis and allergies.Here,we designed an amorphous nanocrystal drug complex(IHNC),which is stabilizer-free and composed of indocyanine green(ICG)framework loading with a chemotherapeutic agent of 10-hydroxycamptothecin(HCPT).Considering the possibility of industrial manufacturing,IHNC was simply prepared with the assistance of ferric ion(III)via supramolecular assembly strategy.The theoretical result of Materials Studio simulation indicated that the prepared ICG-Fe(III)framework showed a stable spherical structure with the appropriate cavity for encapsulating the two drugs of HCPT and ICG with equal mass ratio.The IHNC was stable at physiological pH,with excellent PTT/PDT efficacy,and in vivo probing characteristics.The nanoscale size and reductive stimuli-responsiveness can be conducive to drug accumulation into the tumor site and rapid unloading of cargo.Moreover,such combination therapy showed synergistic photo/chemotherapy effect against 4T1 breast cancer and its tumor inhibition rate even up to 79.4%.These findings demonstrated that the nanocrystal drug delivery strategy could avoid the use of stabilizers and provide a new strategy for drug delivery for combination therapy.

Touch-Responsive Hydrogel for Biomimetic Flytrap-Like Soft Actuator

Stimuli-responsive hydrogel is regarded as one of the most promising smart soft materials for the next-generation advanced technologies and intelligence robots,but the limited variety of stimulus has become a non-negligible issue restricting its further development.Herein,we develop a new stimulus of“touch”(i.e.,spatial contact with foreign object)for smart materials and propose a flytrap-inspired touch-responsive polymeric hydrogel based on supersaturated salt solution,exhibiting multiple responsive behaviors in crystallization,heat releasing,and electric signal under touch stimulation.Furthermore,utilizing flytrap-like cascade response strategy,a soft actuator with touch-responsive actuation is fabricated by employing the touch-responsive hydrogel and the thermo-responsive hydrogel.This investigation provides a facile and versatile strategy to design touch-responsive smart materials,enabling a profound potential application in intelligence areas.

Remotely Activated Nanoparticles for Anticancer Therapy

Cancer has nowadays become one of the leading causes of death worldwide.Conventional anticancer approaches are associated with different limitations.Therefore,innovative methodologies are being investigated,and several researchers propose the use of remotely activated nanoparticles to trigger cancer cell death.The idea is to conjugate two different components,i.e.,an external physical input and nanoparticles.Both are given in a harmless dose that once combined together act synergistically to therapeutically treat the cell or tissue of interest,thus also limiting the negative outcomes for the surrounding tissues.Tuning both the properties of the nanomaterial and the involved triggering stimulus,it is possible furthermore to achieve not only a therapeutic effect,but also a powerful platform for imaging at the same time,obtaining a nano-theranostic application.In the present review,we highlight the role of nanoparticles as therapeutic or theranostic tools,thus excluding the cases where a molecular drug is activated.We thus present many examples where the highly cytotoxic power only derives from the active interaction between different physical inputs and nanoparticles.We perform a special focus on mechanical waves responding nanoparticles,in which remotely activated nanoparticles directly become therapeutic agents without the need of the administration of chemotherapeutics or sonosensitizing drugs.

External-stimuli responsive systems for cancer theranostic

The upsurge of novel nanomaterials and nanotechnologies has inspired the researchers who are striving for designing safer and more efficient drug delivery systems for cancer therapy.Stimuli responsive nanomaterial offered an alternative to design controllable drug delivery system on account of its spatiotemporally controllable properties. Additionally, external stimuli(light, magnetic field and ultrasound) could develop into theranostic applications for personalized medicine use because of their unique characteristics. In this review, we give a brief overview about the significant progresses and challenges of certain externalstimuli responsive systems that have been extensively investigated in drug delivery and theranostics within the last few years.

Recent studies of Pickering emulsion system in petroleum treatment:The role of particles

Pickering emulsions stabilized by solid particles have gained much attention,which afford high stability,low toxicity,controllable rheological properties and stimuli-responsive behavior compared to the traditional emulsions emulsified by surfactants.Those particles,as the core parts of the emulsion systems,play an important role in the fabrication and application of Pickering emulsion systems,making them attractive in petroleum fields.In this review,the influence of various particles on the stability and properties of Pickering emulsion systems as well as recent researches associated with the stimuliresponsibility of Pickering emulsion systems are introduced.Specifically,the design of functional particles and Pickering emulsion systems with super stabilities and controllable rheological properties are listed.Furthermore,some petroleum application of Pickering emulsion systems for enhanced oil recovery and spilled oil collection as well as the application as soft templates to fabricate oil-absorbing material and as three-phase microreactors that most likely for petroleum application are discussed,and the issues hindering the actual application of Pickering emulsion systems are also evaluated.This review charts a way for Pickering emulsion studies that could lead to a valid petroleum application through design of the particles served as the enhancers of Pickering emulsion stability for purpose of tailoring chemical flooding.