Stimuli-responsive Drug Delivery Research Articles

Advances in the stimuli-responsive mesoporous silica nanoparticles as drug delivery system nanotechnology for controlled release and cancer therapy.

Mesoporous silica nanoparticles (MSN) have attracted widespread attention in the field of drug delivery and biomedicine due to their unique structure and physicochemical properties. However, MSN still have shortcomings, such as premature drug release, poorly controlled release ability and poor targeting. Therefore, in order to reduce the damage of anti-cancer drugs to normal cells, improve their utilization rate and realize their selective release in tumor cells, "gated" stimuli-responsive mesoporous silicon nanomaterials as antitumor drug delivery carriers have attracted widespread interest among researchers. The "gated" stimuli-responsive nanovalves drug delivery system can only be removed under certain specific stimuli, which makes the drug maintain "zero release" before reaching the lesion site and achieve drug accumulation in tumor cells, effectively reducing the toxic and side effects on normal cells or tissues, and greatly exerting the efficacy of anti-cancer drugs. Therefore, the construction of stimuli-responsive nano-drug delivery systems have great application potential and significance in cancer treatment and controlled release of anti-cancer drugs. This review article emphasizes the research progress of the "gated" stimuli-responsive MSN (e.g. pH, redox potential, enzyme, temperature and light) or controlled drug release and cancer treatment since 2019.

Boolean logic in synthetic biology and biomaterials: Towards living materials in mammalian cell therapeutics.

The intersection of synthetic biology and biomaterials promises to enhance safety and efficacy in novel therapeutics. Both fields increasingly employ Boolean logic, which allows for specific therapeutic outputs (e.g., drug release, peptide synthesis) in response to inputs such as disease markers or bio-orthogonal stimuli. Examples include stimuli-responsive drug delivery devices and logic-gated chimeric antigen receptor (CAR) T cells. In this review, we explore recent manuscripts highlighting the potential of synthetic biology and biomaterials with Boolean logic to create novel and efficacious living therapeutics. Collaborations in synthetic biology and biomaterials have led to significant advancements in drug delivery and cell therapy. Borrowing from synthetic biology, researchers have created Boolean-responsive biomaterials sensitive to multiple inputs including pH, light, enzymes and more to produce functional outputs such as degradation, gel-sol transition and conformational change. Biomaterials also enhance synthetic biology, particularly CAR T and adoptive T cell therapy, by modulating therapeutic immune cells in vivo. Nanoparticles and hydrogels also enable in situ generation of CAR T cells, which promises to drive down production costs and expand access to these therapies to a larger population. Biomaterials are also used to interface with logic-gated CAR T cell therapies, creating controllable cellular therapies that enhance safety and efficacy. Finally, designer cells acting as living therapeutic factories benefit from biomaterials that improve biocompatibility and stability in vivo. By using Boolean logic in both cellular therapy and drug delivery devices, researchers have achieved better safety and efficacy outcomes. While early projects show incredible promise, coordination between these fields is ongoing and growing. We expect that these collaborations will continue to grow and realize the next generation of living biomaterial therapeutics.

Nanofiber Scaffolds as Drug Delivery Systems Promoting Wound Healing.

Nanofiber scaffolds have emerged as a revolutionary drug delivery platform for promoting wound healing, due to their unique properties, including high surface area, interconnected porosity, excellent breathability, and moisture absorption, as well as their spatial structure which mimics the extracellular matrix. However, the use of nanofibers to achieve controlled drug loading and release still presents many challenges, with ongoing research still exploring how to load drugs onto nanofiber scaffolds without loss of activity and how to control their release in a specific spatiotemporal manner. This comprehensive study systematically reviews the applications and recent advances related to drug-laden nanofiber scaffolds for skin-wound management. First, we introduce commonly used methods for nanofiber preparation, including electrostatic spinning, sol-gel, molecular self-assembly, thermally induced phase separation, and 3D-printing techniques. Next, we summarize the polymers used in the preparation of nanofibers and drug delivery methods utilizing nanofiber scaffolds. We then review the application of drug-loaded nanofiber scaffolds for wound healing, considering the different stages of wound healing in which the drug acts. Finally, we briefly describe stimulus-responsive drug delivery schemes for nanofiber scaffolds, as well as other exciting drug delivery systems.

Surface-Initiated Polymerizations Mediated by Novel Germanium-Based Photoinitiators.

Since surface-initiated photopolymerization techniques have gained increasing interest within the last decades, the coupling of photoinitiators to surfaces and particles has become an important research topic in material and surface sciences. In terms of surface modification and functionalization, covalently coupled photoinitiators and subsequent photopolymerizations are employed to provide a huge variety of surface properties, such as wettability, stimulus responsive features, antifouling behavior, protein binding, friction control, drug delivery, and many more. For this purpose, numerous type I and type II photoinitiators or other photosensitive moieties have been attached to different substrates so far. In our studies, a convenient and straightforward synthetic protocol to prepare a novel germanium-based photoinitiator (bromo-tris(2,4,6-trimethylbenzoyl)germane) in good yields was developed. The immobilization of this photoinitiator at the surface of silicon wafers and quartz plates was evidenced by X-ray photoelectron spectroscopy (XPS). Employing visible-light-triggered surface-initiated polymerization of different functional monomers, including acrylamide, perfluorodecyl acrylate, and fluorescein-o-acrylate, surfaces with various features such as hydrophilic/hydrophobic and fluorescent properties were prepared. This was also achieved in a spatially resolved manner. The polymer layers were characterized by contact angle measurements, UV-vis/fluorescence spectroscopy, spectroscopic ellipsometry, and XPS. The thicknesses of the surface grafted polymer layers ranged between 10 and 126 nm.

K-Carrageenan based magnetic@polyelectrolyte complex composite hydrogel for pH and temperature-responsive curcumin delivery

The dual stimuli-responsive drug delivery system has attracted a lot of interest in controlled drug delivery to specific sites. The magnetic iron oxide nanoparticles integrated polyelectrolyte complex-based hydrogel (MPEC HG) system was developed in this work. First, magnetic nanoparticles were produced in situ in the synthetic polymer polyhexamethylene guanidine (PHMG). Furthermore, the natural biopolymer k-carrageenan (kCG) was employed to form the polyelectrolyte complex (PEC) through charge-balancing interaction between positively charged guanidine units and negatively charged sulfonate groups. Various characterization approaches were used to characterize the developed magnetic polyelectrolyte complex hydrogel (MPEC HG) system. Curcumin (Cur) was employed as a model bioactive agent to examine the drug loading and stimuli-responsive drug release efficiency of the MPEC HG system. Under the combined pH and temperature stimuli conditions (pH 5.0/42 °C), the developed hydrogel system demonstrated great drug loading efficiency (∼ 68 %) and enhanced drug release. Furthermore, the MPEC HG system's in vitro cytotoxicity behavior was investigated on a human liver cancer (HepG2) cell line, and the results revealed that the MPEC HG system is biocompatible. As a result, the MPEC HG system might be used for dual pH and temperature stimuli-responsive drug delivery applications in cancer therapy.

Drug Delivery Systems for Personal Healthcare by Smart Wearable Patch System.

Smart wearable patch systems that combine biosensing and therapeutic components have emerged as promising approaches for personalized healthcare and therapeutic platforms that enable self-administered, noninvasive, user-friendly, and long-acting smart drug delivery. Sensing components can continuously monitor physiological and biochemical parameters, and the monitoring signals can be transferred to various stimuli using actuators. In therapeutic components, stimuli-responsive carrier-based drug delivery systems (DDSs) provide on-demand drug delivery in a closed-loop manner. This review provides an overview of the recent advances in smart wearable patch systems, focusing on sensing components, stimuli, and therapeutic components. Additionally, this review highlights the potential of fully integrated smart wearable patch systems for personalized medicine. Furthermore, challenges associated with the clinical applications of this system and future perspectives are discussed, including issues related to drug loading and reloading, biocompatibility, accuracy of sensing and drug delivery, and largescale fabrication.

L-lysine Functionalized Mesoporous Silica Hybrid Nanoparticles for pH-Responsive Delivery of Curcumin.

Stimuli-responsive controlled drug delivery systems have attracted the attention of researchers in recent decades due to their potential application in developing efficient drug carriers that are responsive to applied stimuli triggers. In this work, we present the synthesis of L-lysine (an amino acid that combines both amine and carboxylic acid groups in a single unit) modified mesoporous silica nanoparticles (MS@Lys NPs) for the delivery of the anticancer bioactive agent (curcumin, Cur) to cancer cells. To begin, mesoporous silica hybrid nanoparticles (MS@GPTS NPs) with 3-glycidoxypropyl trimethoxy silane (GPTS) were synthesized. The L-lysine groups were then functionalized onto the mesopore channel surfaces of the MS@GPTS NPs through a ring-opening reaction between the epoxy groups of the GPTS and the amine groups of the L-lysine units. Several instrumental techniques were used to examine the structural properties of the prepared L-lysine-modified mesoporous silica nanoparticles (MS@Lys NPs). The drug loading and pH-responsive drug delivery behavior of MS@Lys NPs were studied at different pH levels (pH 7.4, 6.5, and 4.0) using curcumin (Cur) as a model anticancer bioactive agent. The MS@Lys NPs' in vitro cytocompatibility and cell uptake behavior were also examined using MDA-MB-231 cells. The experimental results imply that MS@Lys NPs might be used in cancer therapy as pH-responsive drug delivery applications.

Silane-Functionalized Metal-Organic Frameworks for Stimuli-Responsive Drug Delivery Systems: A New Universal Strategy.

A new universal strategy for silane functionalization of metal-organic frameworks (MOFs) was developed. It was demonstrated that silanes were coupled both with terminal hydroxyl (OH) groups and with bridging OH groups of metal-oxo clusters of MOFs through condensation reactions between the silanols of hydrolyzed silanes and the terminal/bridging OH groups to form metal-O-Si bonds. A wide variety of functionalization of MOFs with conventional silanes can be realized by combining synthesis reactions in the solution phase and chemical modifications on the surface. Multivalent supramolecular nanovalves based on the host-guest chemistry of cyclodextrin polymer (CDP) and benzimidazole stalks silanized on the nanoscale MOF (NMOF) surface were successfully constructed. The CDP-valved NMOFs showed the excellent performance of low pH- and α-amylase-responsive controlled drug release. In vitro and in vivo results demonstrated that the CDP-valved NMOFs had a significant inhibitory effect on tumor growth and almost no damage/toxicity to normal tissues. The silanization strategy is universal and opens up a new way for the functionalization of MOFs, which are endowed with a wide variety of applications spanning gas storage, chemical sensing, adsorption and separation, heterogeneous catalysis, and drug delivery.

Nanofiber-Based Systems for Stimuli-Responsive and Dual Drug Delivery: Present Scenario and the Way Forward.

Drug delivery and delivery systems are among the most important research disciplines today, and the relevance of nanofibers in achieving the appropriate release profile at specified sites for increased therapeutic advantages cannot be understated. Nanofiber-based drug delivery systems are fabricated and modified using a range of methods that entail a variety of factors and processes; tuning of these allows control of the drug release such as targeted, extended, multistage, and stimuli-responsive release. We explore nanofiber-based drug delivery systems from the most recent accessible literature, focusing on materials, techniques, modifications, drug release, applications, and challenges. This review offers a thorough assessment of the current and future potential of nanofiber-based drug delivery systems, with a particular emphasis on their capabilities in stimuli-responsive and dual drug delivery. The review begins with an introduction to the important characteristics of nanofibers that are useful in drug delivery applications, followed by materials and synthesis procedures for various types of nanofibers, as well as their practicality and scalability. The review then focuses on and explores the modification and functionalization strategies of nanofibers as essential features for regulating the applications of nanofibers in drug loading, transport, and release. Finally, this review investigates the range of nanofiber-based drug delivery systems in satisfying the current requirements by pointing out the areas that need improvement, followed by critical analysis, and offers probable solutions.

Anisotropic, Hydrogel Microparticles as pH-Responsive Drug Carriers for Oral Administration of 5-FU.

In the last 20 years, the development of stimuli-responsive drug delivery systems (DDS) has received great attention. Hydrogel microparticles represent one of the candidates with the most potential. However, if the role of the cross-linking method, polymer composition, and concentration on their performance as DDS has been well-studied, still, a lot needs to be explained regarding the effect caused by the morphology. To investigate this, herein, we report the fabrication of PEGDA-ALMA-based microgels with spherical and asymmetric shapes for 5-fluorouracil (5-FU) on-demand loading and in vitro pH-triggered release. Due to anisotropic properties, the asymmetric particles showed an increased drug adsorption and higher pH responsiveness, which in turn led to a higher desorption efficacy at the target pH environment, making them an ideal candidate for oral administration of 5-FU in colorectal cancer. The cytotoxicity of empty spherical microgels was higher than the cytotoxicity of empty asymmetric microgels, suggesting that the gel network's mechanical proprieties of anisotropic particles were a better three-dimensional environment for the vital functions of cells. Upon treatment with drug-loaded microgels, the HeLa cells' viability was lower after incubation with asymmetric particles, confirming a minor release of 5-FU from spherical particles.

Facile construction of irinotecan loaded mesoporous nano-formulation with surface-initiated polymerization to improve stimuli-responsive drug delivery for breast cancer therapy

This work uses rice husk to fabricate mesoporous silica nanoparticles (D-RMN) for breast cancer therapy. The biocompatible dual-responsive (DAN-RMN) was developed by polymerizing acrylic acid (AA) and n-isopropyl acrylamide (NIPAM) on the DV-RMN surface monomeric ratio to increase drug delivery efficiency after vinyl groups were added to the surface of nanoparticles (DAN-RMN). Various analytical and spectroscopical methods characterized the fabricated nanoparticles. Additionally, further encapsulation with SN-38 into the DAN-RMN enhances anticancer efficiency. The in-vitro controlled SN-38 release displayed remarkable temperature and pH response. The MTT assay established the biocompatibility and cytotoxicity of natural sources of silica and DAN-RMN. The fabricated SN-38@DAN-RMN nanoparticles effectively killed the MDA-MB-231 and 4T1 cancerous cells, confirmed by the MTT assay. The IC50 values of SN-38@DAN-RMN in MDA-MB-231 and 4T1 for 1.8 μg/mL and 1.7 μg/mL, respectively. In addition, acridine orange-ethidium bromide (AO-EB) dual staining methods were used to determine morphological changes of cell shrinkage and fragmentation. Nuclear staining methods confirmed the nuclear fragmentation and condensation of the cells. Further, the cell death was examined using dual staining Annexin V-FITC/PI in flow cytometric analyses to assess apoptosis in the MDA-MB-231 and 4T1 cell lines. The apoptotic cell ratio of SN-38@DAN-RMN in MDA-MB-231 and 4T1 for 27.8 and 32.8, respectively. Since there is no drug leakage in the blood while the carrier is in circulation, the DAN-RMN nanocarrier may be used for targeted and stimuli-responsive administration using ultrasound imaging.

Stimuli-Responsive Silica Silanol Conjugates: Strategic Nanoarchitectonics in Targeted Drug Delivery.

The design of novel drug delivery systems is exceptionally critical in disease treatments. Among the existing drug delivery systems, mesoporous silica nanoparticles (MSNs) have shown profuse promise owing to their structural stability, tunable morphologies/sizes, and ability to load different payload chemistry. Significantly, the presence of surface silanol groups enables functionalization with relevant drugs, imaging, and targeting agents, promoting their utility and popularity among researchers. Stimuli-responsive silanol conjugates have been developed as a novel, more effective way to conjugate, deliver, and release therapeutic drugs on demand and precisely to the selected location. Therefore, it is urgent to summarize the current understanding and the surface silanols' role in making MSN a versatile drug delivery platform. This review provides an analytical understanding of the surface silanols, chemistry, identification methods, and their property-performance correlation. The chemistry involved in converting surface silanols to a stimuli-responsive silica delivery system by endogenous/exogenous stimuli, including pH, redox potential, temperature, and hypoxia, is discussed in depth. Different chemistries for converting surface silanols to stimuli-responsive bonds are discussed in the context of drug delivery. The critical discussion is culminated by outlining the challenges in identifying silanols' role and overcoming the limitations in synthesizing stimuli-responsive mesoporous silica-based drug delivery systems.

Stimulus-Responsive Drug Delivery Nanoplatforms for Osteoarthritis Therapy.

Osteoarthritis (OA) is one of the most prevalent age-related degenerative diseases. With an increasingly aging global population, greater numbers of OA patients are providing clear economic and societal burdens. Surgical and pharmacological treatments are the most common and conventional therapeutic strategies for OA, but often fall considerably short of desired or optimal outcomes. With the development of stimulus-responsive nanoplatforms has come the potential for improved therapeutic strategies for OA. Enhanced control, longer retention time, higher loading rates, and increased sensitivity are among the potential benefits. This review summarizes the advanced application of stimulus-responsive drug delivery nanoplatforms for OA, categorized by either those that depend on endogenous stimulus (reactive oxygen species, pH, enzyme, and temperature), or those that depend on exogenous stimulus (near-infrared ray, ultrasound, magnetic fields). The opportunities, restrictions, and limitations related to these various drug delivery systems, or their combinations, are discussed in areas such as multi-functionality, image guidance, and multi-stimulus response. The remaining constraints and potential solutions that are represented by the clinical application of stimulus-responsive drug delivery nanoplatforms are finally summarized.

Boosting immunogenic cell death via hollow MnO2-based multiple stimuli-responsive drug delivery systems for improved cancer immunotherapy

Cancer treatment by inducing tumor cell immunogenic cell death (ICD) is critical for tumor therapy. However, ICD activation by single pathway is often limited in practical application due to its low efficiency. In addition, the low pH and anoxic microenvironments in solid tumors greatly limit the effective activation of ICD. Herein, hollow manganese dioxide (H-MnO2) nanomaterials were selected to load both Mitoxantrone (MTZ) and Chlorin e6 (Ce6) due to its hollow structure and ability to release drugs in the acidic environments. Thus, the synergy of photodynamic therapy (PDT), photothermal therapy (PTT) and chemotherapy can induce the process of immunogenic cell death, stimulate the maturation of dendritic cells (DCs), and activate the immune response to kill tumor cells dramatically. Efficient immunotherapeutic effects were obtained when MnO2-C/M-HA was given intravenously to 4T1 tumor-bearing BALB/c mice with 660 nm near-infrared laser irradiation. This study overcame the limitations of monotherapy and provided a multifunctional platform for tumor immunotherapy.

Paclitaxel-Loaded Lipid-Coated Magnetic Nanoparticles for Dual Chemo-Magnetic Hyperthermia Therapy of Melanoma.

Melanoma is the most aggressive and metastasis-prone form of skin cancer. Conventional therapies include chemotherapeutic agents, either as small molecules or carried by FDA-approved nanostructures. However, systemic toxicity and side effects still remain as major drawbacks. With the advancement of nanomedicine, new delivery strategies emerge at a regular pace, aiming to overcome these challenges. Stimulus-responsive drug delivery systems might considerably reduce systemic toxicity and side-effects by limiting drug release to the affected area. Herein, we report the development of paclitaxel-loaded lipid-coated manganese ferrite magnetic nanoparticles (PTX-LMNP) as magnetosomes synthetic analogs, envisaging the combined chemo-magnetic hyperthermia treatment of melanoma. PTX-LMNP physicochemical properties were verified, including their shape, size, crystallinity, FTIR spectrum, magnetization profile, and temperature profile under magnetic hyperthermia (MHT). Their diffusion in porcine ear skin (a model for human skin) was investigated after intradermal administration via fluorescence microscopy. Cumulative PTX release kinetics under different temperatures, either preceded or not by MHT, were assessed. Intrinsic cytotoxicity against B16F10 cells was determined via neutral red uptake assay after 48 h of incubation (long-term assay), as well as B16F10 cells viability after 1 h of incubation (short-term assay), followed by MHT. PTX-LMNP-mediated MHT triggers PTX release, allowing its thermal-modulated local delivery to diseased sites, within short timeframes. Moreover, half-maximal PTX inhibitory concentration (IC50) could be significantly reduced relatively to free PTX (142,500×) and Taxol® (340×). Therefore, the dual chemo-MHT therapy mediated by intratumorally injected PTX-LMNP stands out as a promising alternative to efficiently deliver PTX to melanoma cells, consequently reducing systemic side effects commonly associated with conventional chemotherapies.

Ultrasound-mediated nano drug delivery for treating cancer: Fundamental physics to future directions.

The application of biocompatible nanocarriers in medicine has provided several benefits over conventional treatment methods. However, achieving high treatment efficacy and deep penetration of nanocarriers in tumor tissue is still challenging. To address this, stimuli-responsive nano-sized drug delivery systems (DDSs) are an active area of investigation in delivering anticancer drugs. While ultrasound is mainly used for diagnostic purposes, it can also be applied to affect cellular function and the delivery/release of anticancer drugs. Therapeutic ultrasound (TUS) has shown potential as both a stand-alone anticancer treatment and a method to induce targeted drug release from nanocarrier systems. TUS approaches have been used to overcome various physiological obstacles, including endothelial barriers, the tumor microenvironment (TME), and immunological hurdles. Combining nanomedicine and ultrasound as a smart DDS can increase in situ drug delivery and improve access to impermeable tissues. Furthermore, smart DDSs can perform targeted drug release in response to distinctive TMEs, external triggers, or dual/multi-stimulus. This results in enhanced treatment efficacy and reduced damage to surrounding healthy tissue or organs at risk. Integrating DDSs and ultrasound is still in its early stages. More research and clinical trials are required to fully understand ultrasound's underlying physical mechanisms and interactions with various types of nanocarriers and different types of cells and tissues. In the present review, ultrasound-mediated nano-sized DDS, specifically focused on cancer treatment, is presented and discussed. Ultrasound interaction with nanoparticles (NPs), drug release mechanisms, and various types of ultrasound-sensitive NPs are examined. Additionally, in vitro, in vivo, and clinical applications of TUS are reviewed in light of the critical challenges that need to be considered to advance TUS toward an efficient, secure, straightforward, and accessible cancer treatment. This study also presents effective TUS parameters and safety considerations for this treatment modality and gives recommendations about system design and operation. Finally, future perspectives are considered, and different TUS approaches are examined and discussed in detail. This review investigates drug release and delivery through ultrasound-mediated nano-sized cancer treatment, both pre-clinically and clinically.

Ultrasound-Activatable g-C3 N4 -Anchored Titania Heterojunction as an Intracellular Redox Homeostasis Perturbator for Augmented Oncotherapy.

Energyband structure of inorganic nano-sonosensitizers is usually optimized by surface decoration with noble metals or metal oxide semiconductors, aiming to enhance interfacial charge transfer, augment spin-flip and promote radical generation. To avoid potential biohazards of metallic elements, herein, metal-free graphitic carbon nitride quantum dots (g-C3 N4 QDs) are anchored onto hollow mesoporous TiO2 nanostructure to formulate TiO2 @g-C3 N4 heterojunction. The direct Z-scheme charge transfer significantly improves the separation/recombination dynamics of electron/hole (e- /h+ ) pairs upon ultrasound (US) stimulation, which promotes the yield of singlet oxygen (1 O2 ) and hydroxyl radicals (·OH). The conjugated g-C3 N4 QDs with peroxidase-mimic activity further react with the elevated endogenous H2 O2 and aggravate oxidative stress. After loading prodrug romidepsin (RMD) in TiO2 @g-C3 N4 , stimulus-responsive drug delivery can be realized by US irradiation. The disulfide bridge of the released RMD tends to be reduced by glutathione (GSH) into a monocyclic dithiol, which arrests cell cycle in G2/M phase and evokes apoptosis through enhanced histone acetylation. Importantly, reactive oxygen species accumulation accompanied by GSH depletion is devoted to deleterious redox dyshomeostasis, leading to augmented systemic oncotherapy by eliciting antitumor immunity. Collectively, this paradigm provides useful insights inoptimizing the performance of TiO2 -based nano-sonosensitizers for tackling critical diseases.

A synthetic optimization study on thermoresponsive core cross-linked starpolymers (CCSs)

The well-defined starpolymers can offer a precise stimuli-responsive drug delivery system (SDDS). For this, core cross-linked starpolymers (CCSs) using the poly(N-isopropylacrylamide)-b-poly(n-butyl acrylate) (PNB) linear arm chain and ethylene glycol diacrylate (EGDA) cross-linker were designed and synthesized by the reversible addition-fragmentation chain transfer (RAFT) system. The important synthetic parameters, including reaction time, radical concentration, and cross-linker concentration, were varied to optimize the reaction conditions for highly uniform PNiPAM-based amphiphilic starpolymers (PNBA). The reaction was monitored by GPC, resulting in the sharp monomodal PNBA GPC curve with an almost degraded original curve corresponding to the PNB linear chain. The PNBA revealed a dramatic size increase from 150 nm to 15,000 nm when the temperature increased up to 40 °C. Notably, the uniform CCS structure gives rise to a particular phase transformation system, which can be helpful in biomedical and catalytic applications with enhanced performance.

Graphene-based nanomaterials for stimuli-sensitive controlled delivery of therapeutic molecules.

Stimuli-responsive drug delivery has attracted tremendous attention in the past decades. It provides a spatial- and temporal-controlled release in response to different triggers, thus enabling highly efficient drug delivery and minimizing drug side effects. Graphene-based nanomaterials have been broadly explored, and they show great potential in smart drug delivery due to their stimuli-responsive behavior and high loading capacity for an extended range of drug molecules. These characteristics are a result of high surface area, mechanical stability and chemical stability, and excellent optical, electrical, and thermal properties. Their great and infinite functionalization potential also allows them to be integrated into several types of polymers, macromolecules, or other nanoparticles, leading to the fabrication of novel nanocarriers with enhanced biocompatibility and trigger-sensitive properties. Thus, numerous studies have been dedicated to graphene modification and functionalization. In the current review, we introduce graphene derivatives and different graphene-based nanomaterials utilized in drug delivery and discuss the most important advances in their functionalization and modification. Also, their potential and progress in an intelligent drug release in response to different types of stimuli either endogenous (pH, redox conditions, and reactive oxygen species (ROS)) or exogenous (temperature, near-infrared (NIR) radiation, and electric field) will be debated.

Biomimetic retractable DNA nanocarrier with sensitive responsivity for efficient drug delivery and enhanced photothermal therapy

BackgroundThe coalition of DNA nanotechnology with diversiform inorganic nanoparticles offers powerful tools for the design and construction of stimuli-responsive drug delivery systems with spatiotemporal controllability, but it remains challenging to achieve high-density oligonucleotides modification close to inorganic nanocores for their sensitive responsivity to optical or thermal signals.ResultsInspired by Actinia with retractable tentacles, here we design an artificial nano-Actinia consisted of collapsible DNA architectures attached on gold nanoparticle (AuNP) for efficient drug delivery and enhanced photothermal therapy. The collapsible spheroidal architectures are formed by the hybridization of long DNA strand produced in situ through rolling circle amplification with bundling DNA strands, and contain numerous double-helical segments for the intercalative binding of quercetin as the anti-cancer drug. Under 800-nm light irradiation, the photothermal conversion of AuNPs induces intensive localized heating, which unwinds the double helixes and leads to the disassembly of DNA nanospheres on the surface of AuNPs. The consequently released quercetin can inhibit the expression of heat shock protein 27 and decrease the thermal resistance of tumor cells, thus enhancing photothermal therapy efficacy.ConclusionsBy combining the deformable DNA nanostructures with gold nanocores, this Actinia-mimetic nanocarrier presents a promising tool for the development of DNA-AuNPs complex and opens a new horizon for the stimuli-responsive drug delivery.Graphical