Stimuli-responsive Nanocarriers Research Articles

Mesoporous silica nanoparticles based on a dual environmental response corresponding to temperature and α-amylase for the control of Spodoptera litura

The design and development of stimuli-responsive nanocarriers hold the promise of the smart delivery of pesticides to target organisms. Herein, we successfully prepared mesoporous silica nanoparticles using the self-templating method, which were grafted with both N-isopropylacrylamide (NIPAM) and cyclodextrin (CD) and loaded with indoxacarb (IN) to afford a pesticide release system with a dual-stimulated response of temperature and α-amylase, referred to as IN@MSNs@NIPAM@CD. Physicochemical characterisation revealed the successful preparation of IN@MSNs@NIPAM@CD with 46.30 % indoxacarb loading. The results showed that IN@MSNs@NIPAM@CD was able to release IN rapidly in the environment of high temperature and α-Amylase, with excellent dual-responsive property. The UV resistance evaluation showed that IN@MSNs@NIPAM@CD could effectively improve the photodegradation resistance of indoxacarb. Fluorescent inverted microscope showed that FITC@MSNs@NIPAM@CD has excellent uptake and translocation properties in corn plants. Bioactivity tests showed that at 14 d, IN@MSNs@NIPAM@CD (LC50 = 9.83 mg L−1) exhibited higher insecticidal activity and longer effective duration than IN@EC (LC50 = 14.64 mg L−1). Acute toxicity test revealed that the IN@MSNs@NIPAM@CD nanoparticles were less acutely toxic to earthworms, zebrafish, BEAS-2B cells and MSNs@NIPAM@CD nanocarriers were safe for the growth of corn. Thus, the dual-responsive nano-controlled-release formulation of IN@MSNs@NIPAM@CD can provide an effective way of achieving the precise delivery and reduced use of pesticides.

Recent advances in polymeric and lipid stimuli-responsive nanocarriers for cell-based cancer immunotherapy.

Conventional cancer therapy has major limitations, including non-specificity, unavoidable side effects, low specific tumor accumulation and systemic toxicity. In recent years, more effective and precise treatment methods have been developed, including cell-based immunotherapy. Carriers that can accurately and specifically target cells and equip them to combat cancer cells are particularly important for developing this therapy. As a result, attention has been drawn to smart nanocarriers that can react to specific stimuli. Thus, stimuli-responsive nanocarriers have attracted increasing attention because they can change their physicochemical properties in response to stimulus conditions, such as pH, enzymes, redox agents, hypoxia, light and temperature. This review highlights recent advances in various stimuli-responsive nanocarriers, discussing loading, targeted delivery, cellular uptake, biocompatibility and immunomodulation in cell-based immunotherapy. Finally, future challenges and perspectives regarding the possible clinical translation of nanocarriers are discussed.

A Review on Nano Enabled Controlled Release Fertilizers and their Nutrient Release Mechanisms

The imbalance in nutrient release from conventional fertilizers and plant nutrient uptake leads to a surplus accumulation of nutrients in the soil. A key approach to tackle this issue involves the engineering of nano-enabled fertilizers for the controlled release of nutrients to crops. In this context, it is important to understand the strategies for designing and utilizing nano-enabled fertilizers that can effectively regulate nutrient release and enhance nutrient use efficiency (NUE). This review focuses on nano-structured materials that serve as nutrient carriers: nano-clays, hydroxyapatite (HA) nanoparticles, mesoporous silica, carbon-based nanomaterials, polymeric nanoparticles, and other nanomaterials. In addition, the nutrient release mechanisms in controlled release fertilizers (CRFs)/slow-release fertilizers (SRFs) are discussed. The discussion and perspectives presented emphasizes the need for standardized and comprehensive fertilizer evaluation systems, design of multifunctional nanomaterials, and the creation of stimuli-responsive nanocarriers to improve NUE.

Surface Functionalization of WS2 nanosheets with Poly(N-vinylcaprolactam) and vinylacetic acid for targeted drug release in prostate cancer

Stimuli-responsive nanocarriers have gained attention in cancer therapy as a promising strategy because of their ability to enhance treatment efficacy and minimize off-target medication effects. This study introduces a novel nanopolymer responsive to pH and near-infrared (NIR) light as an intelligent carrier for delivering bicalutamide (BCT) into cancer cells. For this, the surface of tungsten disulfide (WS2) nanosheets is modified with temperature-responsive (poly(N-vinylcaprolactam)) and pH-sensitive (vinylacetic acid) polymers and then characterized using TGA, FE-SEM, XRD, and FT-IR techniques. Experimental variables including pH (5.56), temperature (25 °C), and contact time (11.02 min) are optimized using response surface methodology (RSM) and central composite design (CCD), yielding an adsorption efficacy of 99.45 %. The RSM-CCD model’s capability is analyzed using the correlation coefficient (R2) and several statistical error functions, including average relative error (ARE), root mean square error (RMSE), hybrid fractional error function (HYBRID), and Chi-square test (χ2). The in vitro drug release procedure is evaluated at different pH levels (5.6 and 7.4) and temperatures (37 and 50 °C). The results showed a maximum BCT release of 87.2 % within 6 h at 50 °C and pH 5.6, compared to 13.3 % at 37 °C and pH 7.4. Moreover, the BCT-loaded carrier demonstrates complete BCT release (100 %) following 10 min of NIR irradiation at pH 5.6. The kinetic data confirm that the best fit belongs to the zero-order model, and the drug release followed the supercase II transport mechanism.

Advancing Photodynamic Therapy with Nano-Conjugated Hypocrellin: Mechanisms and Clinical Applications.

Hypocrellin-based photodynamic therapy (PDT) is developing as a viable cancer therapeutic option, especially when enhanced by nanoconjugation. This review investigates the methods by which nano-conjugated hypocrellin enhances therapeutic efficacy and precision when targeting cancer cells. These nanoconjugates encapsulate or covalently bind hypocrellin photosensitizers (PSs), allowing them to accumulate preferentially in malignancies. When activated by light, the nanoconjugates produce singlet oxygen and other reactive oxygen species (ROS), resulting in oxidative stress that selectively destroys cancer cells while protecting healthy tissues. We look at how they can be used to treat a variety of cancers. Clinical and preclinical studies show that they have advantages such as increased water solubility, improved tumor penetration, longer circulation times, and tailored delivery, all of which contribute to fewer off-target effects and overall toxicity. Ongoing research focuses on improving these nanoconjugates for better tumor targeting, drug release kinetics, and overcoming biological obstacles. Furthermore, the incorporation of developing technologies such as stimuli-responsive nanocarriers and combination therapies opens exciting opportunities for enhancing hypocrellin-based PDT. In conclusion, the combination of hypocrellin and nanotechnology constitutes a significant approach to cancer treatment, increasing the efficacy and safety of PDT. Future research will seek to create conjugates including hypocrellin, herceptin, and gold nanoparticles to induce apoptosis in human breast cancer cells in vitro, opening possibilities for therapeutic applications.

Drug Release via Ultrasound-Activated Nanocarriers for Cancer Treatment: A Review

Conventional cancer chemotherapy often struggles with safely and effectively delivering anticancer therapeutics to target tissues, frequently leading to dose-limiting toxicity and suboptimal therapeutic outcomes. This has created a need for novel therapies that offer greater efficacy, enhanced safety, and improved toxicological profiles. Nanocarriers are nanosized particles specifically designed to enhance the selectivity and effectiveness of chemotherapy drugs while reducing their toxicity. A subset of drug delivery systems utilizes stimuli-responsive nanocarriers, which enable on-demand drug release, prevent premature release, and offer spatial and temporal control over drug delivery. These stimuli can be internal (such as pH and enzymes) or external (such as ultrasound, magnetic fields, and light). This review focuses on the mechanics of ultrasound-induced drug delivery and the various nanocarriers used in conjunction with ultrasound. It will also provide a comprehensive overview of key aspects related to ultrasound-induced drug delivery, including ultrasound parameters and the biological effects of ultrasound waves.

Navigating the therapeutic landscape for breast cancer: targeting breast cancer stem cells.

Breast cancer is a common and deadly malignancy that affects women globally, and breast cancer stem cells (BCSCs) play an important role in tumorigenesis, development, metastasis, and recurrence. Traditional therapies often fail to eliminate BCSCs, leading to treatment resistance and relapse. This review explores the therapeutic strategies which are designed to target BCSCs, including inhibition of key signaling pathway and targeting receptor. This paper also explores the approaches to targeting BCSCs including chemotherapy, phytomedicines, and nanotechnology. Nanotechnology has gained a lot of importance in cancer therapy because of its ability to deliver therapeutic agents with more precision and minimal side effects. Various chemotherapeutic drugs, siRNAs, or gene editing tools are delivered efficiently with the use of nanocarriers which target pathways, receptors, and proteins associated with BCSCs. Over the past few years, stimuli-responsive and receptor-targeted nanocarriers have been explored for better therapeutic effects. In recent times, strategies such as chimeric antigen receptor (CAR) T-cell therapy, ablation therapy, and cell-free therapies are explored for targeting these stem cells. This review provides a recent developmental overview of strategies to attack BCSCs from conventional chemotherapeutic agents to nanotechnological platforms such as polymeric, lipidic, and metal-based nanoparticles and advanced technologies like CAR T cell therapies.

Two Different Responsive Organosilica Nanocarriers to Combine Chemo- and Immunotherapy against Cancer.

The combination of chemo- and immunotherapy was recently demonstrated to improve a patient's response to therapy, giving rise to an emerging cancer treatment known as chemoimmunotherapy (CIT). Despite the promising benefits of CIT, the most important challenges are (i) the simultaneous or time-controlled delivery of two drugs and (ii) the selective uptake into different cells for each of the drugs: cancer cells for the chemotherapeutic and macrophages for the immunostimulation actives. Herein, a delivery strategy based on morphologically different stimuli-responsive breakable organosilica nanocarriers is exploited to transport two distinct drugs in the different cells using different times of delivery. We employ stimulus-sensitive, PEGylated organosilica nanocages to encapsulate the chemotherapeutic agent doxorubicin, which is preferentially taken up by tumor cells vs macrophages. On the other hand, similar size mesoporous organosilica nanoparticles, preferentially internalized by macrophages, are filled with the immunostimulator resiquimod. The administration in a sequential manner of the two different nanocarriers allowed us to assess the integrated effect of the combined therapy versus treatment with a single drug. In vitro work clearly shows an important reduction of tumor cell viability when both chemo- and immunotherapeutic agents are delivered.

Stimuli-Responsive Polymeric Nanocarriers Accelerate On-Demand Drug Release to Combat Glioblastoma.

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a poor prognosis and limited treatment options. Drug delivery by stimuli-responsive nanocarriers holds great promise for improving the treatment modalities of GBM. At the beginning of the review, we highlighted the stimuli-active polymeric nanocarriers carrying therapies that potentially boost anti-GBM responses by employing endogenous (pH, redox, hypoxia, enzyme) or exogenous stimuli (light, ultrasonic, magnetic, temperature, radiation) as triggers for controlled drug release mainly via hydrophobic/hydrophilic transition, degradability, ionizability, etc. Modifying these nanocarriers with target ligands further enhanced their capacity to traverse the blood-brain barrier (BBB) and preferentially accumulate in glioma cells. These unique features potentially lead to more effective brain cancer treatment with minimal adverse reactions and superior therapeutic outcomes. Finally, the review summarizes the existing difficulties and future prospects in stimuli-responsive nanocarriers for treating GBM. Overall, this review offers theoretical guidelines for developing intelligent and versatile stimuli-responsive nanocarriers to facilitate precise drug delivery and treatment of GBM in clinical settings.

Stimuli-responsive gelatin-coated alginate nanocarriers: Targeted delivery of efflux pump inhibitor and antibacterial agents to control multidrug resistant P. aeruginosa

Multidrug resistance is an inescapable obstacle in healthcare settings. As the over-expression of efflux pumps is an important mediator of bacterial drug resistance, stimuli-responsive co-delivery nanosystems were developed for the sequential release of efflux pump inhibitors (EPI) and antibacterial agents. Gelatin-coated alginate nanocarriers (AlNCs@Gel) were developed containing ciprofloxacin (Cip) and quercetin (Que) as antibacterial/antibiofilm agents and EPI, respectively. Heat plot maps revealed a synergistic interaction of Cip with Que as the minimum inhibitory concentration value of Cip was reduced in the presence of EPI (quercetin) against P. aeruginosa. The encapsulation efficiency of 82 ± 1 % was observed for Cip while it was 70 ± 1 % for Que in Cip/AlNCs@Que/Gel nanocarriers. FTIR analyses confirmed an interaction between alginate and gelatin by the occurrence of a blue shift that is associated with electrostatic interactions between alginate and gelatin. These nanocarriers loaded with quercetin as EPI would release it preferentially in the presence of gelatinase enzyme and subsequently prevent the efflux of ciprofloxacin from bacterial cells. Membrane-permeability assay confirmed no permeabilization while viability studies exhibited superior bacterial inhibition, as Cip/EPI combination encapsulated in AlNCs@Gel effectively controlled the growth of P. aeruginosa as compared to antibiotic alone in AlNCs@Gel and free drug combinations. In vitro, cytotoxicity-analysis confirmed the biocompatibility of the developed core-shell nanocarriers. Furthermore, gelatin coating improved the physico-chemical properties of nanocarriers and the on-demand-release of EPI and antibiotic molecules. Thus, smartly designed AlNCs@Gel nanocarriers for the co-delivery of EPI and antibiotics present an innovative solution for preventing drug efflux from P. aeruginosa to control resistant infections.

Azobenzene-based liposomes with nanomechanical action for cytosolic chemotherapeutic drug delivery

The stimuli-responsive nano-carriers are at the forefront of research in nanotechnology and materials science. These advanced systems are designed to alter their physicochemical properties upon exposure to specific stimuli, enabling controllable and targeted delivery of therapeutic agents. Nevertheless, limited endosomal escape reduces the drug bioavailability in clinical use. We herein report azobenzene (Azo)-based liposomes, prepared by co-assembling the photoisomerizable cationic Azo lipids and helper lipids, which achieve controllable doxorubicin (Dox) release and enhanced cytosolic transport upon light irradiation. Azo lipids undergo reversible isomerization between cis-isomers and trans-isomer when received UV and visible (Vis) light irradiation, causing liposomal membrane permeability changes for controlled drug release. Moreover, the nanomechanical action created by the isomerization of Azo lipids promotes the endosomal escape of the liposomes. DSPC-Azo liposomes, with minimal Dox leakage, showed significant tumor cell killing upon irradiation. For in vivo study, we co-encapsulated the upconverting nanoparticles (UCNPs), which can convert the near-infrared (NIR) light into UV/Vis emissions, facilitating Azo units activation. UCNP/Dox-loaded DSPC-Azo liposomes inhibited tumor growth under NIR irradiation in a 4T1 tumor-bearing mouse model.

Size Control of Chiral Nanospheres Obtained via Nanoprecipitation of Helical Poly(phenylacetylene)s in the Absence of Surfactants.

Nanostructuration of dynamic helical polymers such as poly(phenylacetylene)s (PPAs) depends on the secondary structure adopted by the polymer and the functional group used to connect the chiral pendant to the PPA backbone. Thus, while PPAs with dynamic and flexible scaffolds (para- and meta-substituted, ω1<165°) generate by nanoprecipitation low polydisperse nanospheres with controllable size at different acetone/water mixtures, those with a quasi-static behavior and the presence of an extended, almost planar structure (ortho-substituted, ω1>165°), aggregate into a mixture of spherical and oval nanostructures whose size is not controlled. Photostability studies show that poly(phenylacetylene) particles are more stable to light irradiation than when dissolved macromolecularly. Moreover, the photostability of the particle depends on the secondary structure of the PPA and its screw sense excess. This fact, in combination with the encapsulation ability of these polymer particles, allows the creation of light stimuli-responsive nanocarriers, whose cargo can be delivered by light irradiation.

Parthenolide-Loaded Stimuli-Responsive Cross-Linked Nanocarrier for Targeting and Killing Triple-Negative Breast Cancer Cells

Parthenolide-Loaded Stimuli-Responsive Cross-Linked Nanocarrier for Targeting and Killing Triple-Negative Breast Cancer Cells

Fabrication of Rhenium Disulfide/Mesoporous Silica Core-Shell Nanoparticles for a pH-Responsive Drug Release and Combined Chemo-Photothermal Therapy.

A stimuli-responsive drug delivery nanocarrier with a core-shell structure combining photothermal therapy and chemotherapy for killing cancer cells was constructed in this study. The multifunctional nanocarrier ReS2@mSiO2-RhB entails an ReS2 hierarchical nanosphere coated with a fluorescent mesoporous silica shell. The three-dimensional hierarchical ReS2 nanostructure is capable of effectively absorbing near-infrared (NIR) light and converting it into heat. These ReS2 nanospheres were generated by a hydrothermal synthesis process leading to the self-assembly of few-layered ReS2 nanosheets. The mesoporous silica shell was further coated on the surface of the ReS2 nanospheres through a surfactant-templating sol-gel approach to provide accessible mesopores for drug uploading. A fluorescent dye (Rhodamine B) was covalently attached to silica precursors and incorporated during synthesis in the mesoporous silica walls toward conferring imaging capability to the nanocarrier. Doxorubicin (DOX), a known cancer drug, was used in a proof-of-concept study to assess the material's ability to function as a drug delivery carrier. While the silica pores are not capped, the drug molecule loading and release take advantage of the pH-governed electrostatic interactions between the drug and silica wall. The ReS2@mSiO2-RhB enabled a drug loading content as high as 19.83 mg/g doxorubicin. The ReS2@mSiO2-RhB-DOX nanocarrier's cumulative drug release rate at pH values that simulate physiological conditions showed significant pH responsiveness, reaching 59.8% at pH 6.8 and 98.5% and pH 5.5. The in vitro testing using HeLa cervical cancer cells proved that ReS2@mSiO2-RhB-DOX has a strong cancer eradication ability upon irradiation with an NIR laser owing to the combined drug delivery and photothermal effect. The results highlight the potential of ReS2@mSiO2-RhB nanoparticles for combined cancer therapy in the future.

Persistent Targeting DNA Nanocarrier Made of 3D Structural Unit Assembled from Only One Basic Multi-Palindromic Oligonucleotide for Precise Gene Cancer Therapy.

Construction of a simple, reconfigurable, and stimuli-responsive DNA nanocarrier remains a technical challenge. In this contribution, by designing three palindromic fragments, a simplest four-sticky end-contained 3D structural unit (PS-unit) made of two same DNA components is proposed. Via regulating the rotation angle of central longitudinal axis of PS-unit, theorientedassembly of one-component spherical architecture is accomplished with high efficiency. Introduction of an aptamer and sticky tail warehouse into one component creates a size-change-reversible targeted siRNA delivery nanovehicle. Volume swelling of 20 nm allows one carrier to load 1987 siPLK1s. Once entering cancer cells and responding to glutathione (GSH) stimuli, siPLK1s are almost 100% released and original size of nanovehicle is restored, inhibiting the expression of PLK1 protein and substantially suppressing tumor growth (superiorto commercial transfection agents) in tumor-bearing mice without systemic toxicity.

Dual stimuli-responsive polymeric nanoparticles combining soluplus and chitosan for enhanced breast cancer targeting.

A dual stimuli-responsive nanocarrier was developed from smart biocompatible chitosan and soluplus graft copolymers. The copolymerization was investigated by differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), and Fourier transform infrared (FTIR). The optimized chitosan-soluplus nanoparticles (CS-SP NPs) were further used for the encapsulation of a poorly water-soluble anticancer drug. Tamoxifen citrate (TC) was used as the model drug and it was loaded in CS-SP NPs. TC CS-SP NPs were characterized in terms of particle size, zeta potential, polydispersity, morphology, encapsulation efficiency, and physical stability. The nanoparticles showed homogenous spherical features with a size around 94 nm, a slightly positive zeta potential, and an encapsulation efficiency around 96.66%. Dynamic light scattering (DLS), in vitro drug release, and cytotoxicity confirmed that the created nano-system is smart and exhibits pH and temperature-responsive behavior. In vitro cellular uptake was evaluated by flow cytometry and confocal microscopy. The nanoparticles revealed a triggered increase in size upon reaching the lower critical solution temperature of SP, with 70% of drug release at acidic pH and 40 °C within the first hour and a 3.5-fold increase in cytotoxicity against MCF7 cells incubated at 40 °C. The cellular uptake study manifested that the prepared nanoparticles succeeded in delivering drug molecules to MCF7 and MDA-MB-231 cells. In summary, the distinctive characteristics provided by these novel CS-SP NPs result in a promising nano-platform for effective drug delivery in cancer treatment.

Unveiling innovative therapeutic strategies and future trajectories on stimuli-responsive drug delivery systems for targeted treatment of breast carcinoma.

This comprehensive review delineates the latest advancements in stimuli-responsive drug delivery systems engineered for the targeted treatment of breast carcinoma. The manuscript commences by introducing mammary carcinoma and the current therapeutic methodologies, underscoring the urgency for innovative therapeutic strategies. Subsequently, it elucidates the logic behind the employment of stimuli-responsive drug delivery systems, which promise targeted drug administration and the minimization of adverse reactions. The review proffers an in-depth analysis of diverse types of stimuli-responsive systems, including thermoresponsive, pH-responsive, and enzyme-responsive nanocarriers. The paramount importance of material choice, biocompatibility, and drug loading strategies in the design of these systems is accentuated. The review explores characterization methodologies for stimuli-responsive nanocarriers and probes preclinical evaluations of their efficacy, toxicity, pharmacokinetics, and biodistribution in mammary carcinoma models. Clinical applications of stimuli-responsive systems, ongoing clinical trials, the potential of combination therapies, and the utility of multifunctional nanocarriers for the co-delivery of assorted drugs and therapies are also discussed. The manuscript addresses the persistent challenge of drug resistance in mammary carcinoma and the potential of stimuli-responsive systems in surmounting it. Regulatory and safety considerations, including FDA guidelines and biocompatibility assessments, are outlined. The review concludes by spotlighting future trajectories and emergent technologies in stimuli-responsive drug delivery, focusing on pioneering approaches, advancements in nanotechnology, and personalized medicine considerations. This review aims to serve as a valuable compendium for researchers and clinicians interested in the development of efficacious and safe stimuli-responsive drug delivery systems for the treatment of breast carcinoma.

Stimuli-Responsive Polymer-Based Nanosystems for Cancer Theranostics.

Stimuli-responsive polymers can respond to internal stimuli, such as reactive oxygen species (ROS), glutathione (GSH), and pH, biological stimuli, such as enzymes, and external stimuli, such as lasers and ultrasound, etc., by changing their hydrophobicity/hydrophilicity, degradability, ionizability, etc., and thus have been widely used in biomedical applications. Due to the characteristics of the tumor microenvironment (TME), stimuli-responsive polymers that cater specifically to the TME have been extensively used to prepare smart nanovehicles for the targeted delivery of therapeutic and diagnostic agents to tumor tissues. Compared to conventional drug delivery nanosystems, TME-responsive nanosystems have many advantages, such as high sensitivity, broad applicability among different tumors, functional versatility, and improved biosafety. In recent years, a great deal of research has been devoted to engineering efficient stimuli-responsive polymeric nanosystems, and significant improvement has been made to both cancer diagnosis and therapy. In this review, we summarize some recent research advances involving the use of stimuli-responsive polymer nanocarriers in drug delivery, tumor imaging, therapy, and theranostics. Various chemical stimuli will be described in the context of stimuli-responsive nanosystems. Accordingly, the functional chemical groups responsible for the responsiveness and the strategies to incorporate these groups into the polymer will be discussed in detail. With the research on this topic expending at a fast pace, some innovative concepts, such as sequential and cascade drug release, NIR-II imaging, and multifunctional formulations, have emerged as popular strategies for enhanced performance, which will also be included here with up-to-date illustrations. We hope that this review will offer valuable insights for the selection and optimization of stimuli-responsive polymers to help accelerate their future applications in cancer diagnosis and treatment.

Effective intracellular release of ibuprofen triggered by thermosensitive magnetic nanocarriers.

Stimuli-responsive nanocarriers are being widely applied in the development of new strategies for the diagnosis and treatment of diseases. An inherent difficulty in general drug therapy is the lack of precision with respect to a specific pathological site, which can lead to toxicity, excessive drug consumption, or premature degradation. In this work, the controlled drug delivery is achieved by using magnetite nanoparticles coated with mesoporous silica with core-shell structure (MMS) and grafted with the thermoresponsive polymer poly [N-isopropylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate] (MMS-P). The efficiency of MMS-P as a temperature-controlled drug delivery system was evaluated by in vitro release experiments using ibuprofen (IBU) in various mammalian cell models. Further, the effects of IBU as a photoprotectant in cells exposed to photodynamic therapy (PDT) in a carbaryl-induced neurodegenerative model were evaluated. The results showed that MMS-P nanocarriers do not exhibit cytotoxicity in HepG2 cells at high doses such as 7600µgmL-1. Pre-incubation of MMS-P charged with IBU showed no effect on the PDT in N2A cells; however, it produced a further decrease in the viability of HepG2 cells, leading to a reduction to PDT resistance. On the other hand, a cytoprotective effect against carbaryl toxicity in N2A cells was observed in IBU administrated by MMS-P, which confirms the effective intracellular IBU uptake by means of MMS-P. These results encourage the potential application of MMS-P as a drug delivery system and confirm the effect of IBU as a cytoprotective agent in a neurodegenerative model.

Recent advances on stimuli-responsive biopolymer-based nanocomposites for drug delivery

Drug delivery plays a crucial part in medical therapy, where stimuli-responsive nanocarriers exhibit high delivery efficacy through changing their physicochemical properties in response to in vivo or external stimuli. In particular, biopolymer-based nanocomposites have attracted great attention as drug carriers due to their good biocompatibility, biodegradation, easy modification, low immunogenicity, and so on. They can be designed to transform size, charge and/or stability to prolong the blood circulation, accumulate at the diseased site, penetrate in tissues, internalize to target cells, and finally deliver and control drug release on demand under endogenous stimuli (e.g., acidic pH, enzymes and GSH), exogenous stimuli (e.g., temperature, light, magnetic field, and ultrasound), and both endogenous and exogenous stimuli. Different from the reviews on stimuli-responsive nanocomposites based on single biopolymer or general ideas of biopolymer-based nanocomposites, this paper summarizes strategies and recent progress of stimuli-responsive nanocomposites based on biopolymers such as polysaccharides (chitosan, hyaluronic acid, alginate, cyclodextrin, starch and cellulose) and proteins (gelatin, silk fibroin and collagen), and details their fabrication and application in drug delivery. Furthermore, this review provides evidence and ideas for designing stimuli-responsive nanocomposites for drug delivery.