Fe3O4 assembly for tumor accurate diagnosis by endogenous GSH responsive T2/T1 magnetic relaxation conversion.

Superparamagnetic iron oxide nanoparticles with high magnetization strength and good biological safety have been widely used as magnetic resonance imaging (MRI) contrast agents for tumors. However, the accuracy of tumor diagnosis is still low due to the lack of tumor targeting and the interference signals from normal tissues. Endogenous substances in tumor (such as high levels of GSH and pH) stimuli-responsive contrast agents could offer higher sensitivity for tumor diagnosis. Herein, based on the characteristic of overexpression of GSH in tumors, we propose an ultra-small Fe3O4 assembly as an endogenous GSH responsive MRI contrast agent. The ultra-small superparamagnetic Fe3O4 are bonded to the crosslinker cystamine to synthesize Fe3O4 nanoclusters, which exhibit a T2 imaging effect. When the contrast agent reaches the tumor tissue, the disulfide bond in cystamine is induced by GSH to break, the Fe3O4 nanoclusters are disassembled into ultra-small Fe3O4 nanoparticles, and the relaxation signal changes from T2 to T1, which is helpful for accurate diagnosis of tumors. In vivo experiments have shown that Fe3O4 nanoclusters can rapidly respond to overexpressed GSH in tumor sites for T2/T1 switchable imaging. This work not only designed an endogenous GSH responsive platform through simple synthesis methods, but also improved the accuracy of tumor diagnosis through the transformation of T2/T1 MRI signals.

Multifunctional injectable pluronic-cystamine-alginate-based hydrogel as a novel cellular delivery system towards tissue regeneration.

This paper presents a new thermal sensitive hydrogel system based on cystamine-functionalised sodium alginate-g-pluronic F127 (ACP). The introduction of cystamine to the alginate backbone not only creates a covalent bond with pluronic F127 but also provides intrinsic anti-bacterial activity for the resultant hydrogel. The amount of water uptake inside the hydrogel remained ~200% for 6 days and the degradation was completed in 12 days in physiological media. The ACP copolymer solution could form a hydrogel at body temperature (~37 °C) and could return to the solution phase if the temperature decreased below 25o °C. Fibroblast encapsulated in situ in the ACP hydrogel maintained their viability (≥90% based on the live/dead assay) for 7 days, demonstrating the good biocompatibility of the ACP hydrogel for long-term cell cultivation. In addition, three-dimensional (3D) culture showed that fibroblast attached to the hydrogels and successfully mimicked the porous structure of the ACP hydrogel after 5 days of culture. Fibroblast cells could migrate from the cell-ACP clusters and form a confluent cell layer on the surface of the culture dish. Altogether, the obtained results indicate that the thermal-responsive ACP hydrogel synthesised in this study may serve as a cellular delivery platform for diverse tissue engineering applications.

Application of a Reactive Oxygen Species-Responsive Drug-Eluting Coating for Surface Modification of Vascular Stents.

Stent implantation is the primary method used to treat coronary heart disease. However, it is associated with complications such as restenosis and late thrombosis. Despite surface modification being an effective way to improve the biocompatibility of stents, the current research studies are not focused on changes in the vascular microenvironment at the implantation site. In the present study, an adaptive drug-loaded coating was constructed on the surface of vascular stent materials that can respond to oxidative stress at the site of vascular lesions. Two functional molecules, epigallocatechin gallate (EGCG) and cysteine hydrochloride, were employed to fabricate a coating on the surface of 316L stainless steel. In addition, the coating was used as a drug carrier to load pitavastatin calcium. EGCG has antioxidant activity, and pitavastatin calcium can inhibit smooth muscle cell proliferation. Therefore, EGCG and pitavastatin calcium provided a synergistic anti-inflammatory effect. Moreover, the coating was cross-linked using disulfide bonds, which accelerated the release of the drug in response to reactive oxygen species. A positive correlation was observed between the rate of drug release and the degree of oxidative stress. Collectively, this drug-loaded oxidative stress-responsive coating has been demonstrated to significantly inhibit inflammation, accelerate endothelialization, and reduce the risk of restenosis of vascular stents in vivo.

Glutathione and cystamine functionalized MoS2core-shell nanoparticles for enhanced electrochemical detection of doxorubicin.

Two-dimensional (2D) MoS2core-shell nanoparticles were synthesized using an eco-friendly surface functionalization-agent with L-glutathione and cystamine (L-GSH-MoS2-CYS) using ultrasonic frequency of 20-25 kHz. The novel modified electrode was evaluated for the electrochemical detection of doxorubicin (DOX), through cyclic and differential pulse voltammetric techniques. The electro-catalytic oxidation currents of DOX exhibited a linear relationship in the concentration ranges 0.1-78.3 and 98.3-1218 µM, with a detection limit of 31 nM. A sensitivity of 0.017µA µM-1 cm-2 was acquired at 0.48 V. The fabricated L-GSH-MoS2-CYS modified electrode showed excellent precision, selectivity, repeatability, and reproducibility during the determination of DOX levels in blood serum samples. Thus, the fabricated L-GSH-MoS2-CYS/GCE modified electrode has potential for clinical applications for optimization of chemotherapeutic drugs owing to its selectivity, ease of preparation, and long-term stability. Graphical abstract.

Nondestructive capture, release, and detection of circulating tumor cells with cystamine-mediated folic acid decorated magnetic nanospheres.

Circulating tumor cell (CTC) detection and enumeration have been considered as a noninvasive biopsy method for the diagnosis, characterization, and monitoring of various types of cancers. However, CTCs are exceptionally rare, which makes CTC detection technologically challenging. In the past few decades, much effort has been focused on highly efficient CTC capture, while the activity of CTCs has often been ignored. Here, we develop an effective method for nondestructive CTC capture, release, and detection. Folic acid (FA), as a targeting molecule, is conjugated on magnetic nanospheres through a cleavable disulfide bond-containing linker (cystamine) and a polyethylene glycol (PEG2k) linker, forming MN@Cys@PEG2k-FA nanoprobes, which can bind with folate receptor (FR) positive CTCs specifically and efficiently, leading to the capture of CTCs with an external magnetic field. When approximately 150 and 10 model CTCs were spiked in 1 mL of lysis blood, 93.1 ± 2.9% and 80.0 ± 9.7% CTCs were recovered, respectively. In total, 81.3 ± 2.6% captured CTCs can be released from MN@Cys@PEG2k-FA magnetic nanospheres by treatment with dithiothreitol. The released CTCs are easily identified from blood cells for specific detection and enumeration combined with immunofluorescence staining with a limit of detection of 10 CTC mL-1 lysed blood. Moreover, the released cells remain healthy with high viability (98.6 ± 0.78%) and can be cultured in vitro without detectable changes in morphology or behavior compared with healthy untreated cells. The high viability of the released CTCs may provide the possibility for downstream proteomics research of CTCs; therefore, cultured CTCs were collected for proteomics. As a result, 3504 proteins were identified. In conclusion, the MN@Cys@PEG2k-FA magnetic nanospheres prepared in this study may be a promising tool for early-stage cancer diagnosis and provide the possibility for downstream analysis of CTCs.

Disulfide bridge cross-linking between protein and the RNA backbone as a tool to study RNase H1.

The chemical cross-linking of complexes of proteins with nucleic acids is often used in structural and mechanistic studies of these oftentimes unstable and transient complexes. To date, no method has been reported for the thiol-based conjugation of proteins with an RNA backbone, mainly because of instability of the modified ribonucleic acid that is functionalized at the phosphodiester and its rapid hydrolysis. Here, we report the site-specific synthesis of stable RNA oligonucleotides with a thiol-bearing linker that was attached to the phosphodiester backbone, where the ribonucleotide at the cross-linking site was either replaced with 2'-deoxy- or 2'-fluororibonucleotide. The utility of this approach was validated in cross-linking tests with RNase H1, a model protein for RNA/DNA binding and key effector in DNA-like antisense drug therapy. Furthermore, scale-up cross-linking and purification of the complexes confirmed that the method is useful for obtaining preparations of protein-RNA/DNA complexes with purity and stability that are suitable for further biochemical and structural studies. The present approach broadens the repertoire of disulfide-based cross-linking strategies and is a novel tool for the stabilization of protein-RNA complexes in which the interaction occurs via the RNA backbone. This methodology may be broadly applicable to studies of otherwise unstable or transient complexes of proteins with RNA and RNA/DNA.

Designer Hydrogel with Intelligently Switchable Stem-Cell Contact for Incubating Cartilaginous Microtissues.

Stem-cell-derived organoid can resemble in vivo tissue counterpart and mimic at least one function of tissue or organ, possessing great potential for biomedical application. The present study develops a hydrogel with cell-responsive switch to guide spontaneous and sequential proliferation and aggregation of adipose-derived stem cells (ASCs) without inputting artificial stimulus for in vitro constructing cartilaginous microtissues with enhanced retention of cell-matrix and cell-cell interactions. Polylactic acid (PLA) rods are surface-aminolyzed by cystamine, followed by being involved in the amidation of poly(( l-glutamic acid) and adipic acid dihydrazide (ADH) to form a hydrogel. Along with tubular pore formation in hydrogel after dissolution of PLA rods, aminolyzed PLA molecules with disulfide bonds on rod surfaces are covalently transferred to the tubular pore surfaces of poly(l-glutamic acid)/ADH hydrogel. Because PLA attaches cells, while poly(l-glutamic acid)/ADH hydrogel repels cells, ASCs are found to adhere and proliferate on the tubular pore surfaces of hydrogel first and then cleave disulfide bonds by secreting molecules containing thiol, thus inducing desorption of PLA molecules and leading to their spontaneous detachment and aggregation. Associated with chondrogenic induction by TGF-ß1 and IGF-1 in vitro for 28 days, the hydrogel as an all-in-one incubator produces well-engineered columnar cartilage microtissues from ASCs, with the glycosaminoglycans (GAGs) and collagen type II (COL II) deposition achieving 64 and 69% of those in chondrocytes pellet, respectively. The cartilage microtissues further matured in vivo for 8 weeks to exhibit extremely similar histological features and biomechanical performance to native hyaline cartilage. The GAGs and COL II content, as well as compressive modulus of the matured tissue show no significant difference with native cartilage. The designer hydrogel may hold a promise for long-term culture of other types of stem cells and organoids.

Diversification of polyphosphate end-labeling via bridging molecules.

Investigation of the biological roles of inorganic polyphosphate has been facilitated by our previous development of a carbodiimide-based method for covalently coupling primary amine-containing molecules to the terminal phosphates of polyphosphate. We now extend that approach by optimizing the reaction conditions and using readily available "bridging molecules" containing a primary amine and an additional reactive moiety, including another primary amine, a thiol or a click chemistry reagent such as dibenzocyclooctyne. This two-step labeling method is used to covalently attach commercially available derivatives of biotin, peptide epitope tags, and fluorescent dyes to the terminal phosphates of polyphosphate. Additionally, we report three facile methods for purifying conjugated polyphosphate from excess reactants.

Fabrication of biodegradable auto-fluorescent organosilica nanoparticles with dendritic mesoporous structures for pH/redox-responsive drug release.

In this work, disulfide-bridged organic silica (OS) based nanocarriers were constructed for drug release. The broken of SS bonds in Si-O-Si skeleton would improve the degradation of Si-O-Si of OS carriers. The OS carriers have a central-radiated dendritic porous structure and a large specific surface area of 453.80 m2g-1. The dextrin was selectively oxidized to dialdehyde dextrin (DAD) and then was modified on the surface of OS carriers by Schiff base bonds. Subsequently, cystamine (Cys) was linked with DAD to form DAD/Cys layer (OS-N=C-DAD/Cys) to seal the loaded drug. The DAD/Cys layer display the degradation performance of pH/GSH dual response The obtained OS-N=C-DAD/Cys carriers displayed low premature and the cumulative release was 6.5% under normal physiological conditions within 48 h. The Schiff base (-N=C-) structure in the DAD/Cys layer is also capable of monitoring acid-responsive drug release by fluorescence change. The prepared OS-N=C-DAD/Cys carriers and their degraded products have high biocompatibility.

Development of Stimulus-Responsive Degradable Film via Codeposition of Dopamine and Cystamine.

Herein, we report a degradable film that can be coated on various substrates by the codeposition of dopamine and cystamine. The thickness of the resulting film (pDC) varies depending on the initial ratio of dopamine/cystamine dissolved in a solution; the thickest film (ca. 60 nm) is obtained under optimized codeposition conditions. Selective degradation of pDC occurs in the presence of tris(2-carboxyethyl)phosphine (TCEP), the reaction kinetics of which are highly dependent on the TCEP concentration. For further application as a drug-delivery platform, doxorubicin can be loaded within the pDC film, which is released actively under film degradation in response to TCEP. We expect that the developed pDC film will be a useful tool for developing drug delivery cargo, antibacterial surface, and cell surface coating for various biomedical applications.

Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer.

The present study was intended to develop a papain grafted S-protected hyaluronic acid-lithocholic acid co-block (PAP-HA-ss-LCA) polymeric excipient as an amphiphilic muco permeating stabilizer for targeting breast cancer epithelial cells overexpressed with CD44 receptors. The mucopermeating, stabilizing and targeting capability of the PAP-HA-ss-LCA polymeric excipient was investigated by manufacturing tamoxifen (TMX) loaded self-nanoemulsifying drug delivery system (SNEDDS). TMX loaded PAP-HA-ss-LCA incorporated SNEDDS (TMX-PAP-HA-ss-LCA SNEDDS) were characterized for their surface chemistry, drug release, permeation enhancement, biocompatibility and antitumor activity. FTIR spectroscopic analysis showed successful synthesis of PAP-HA-ss-LCA polymer. X-ray diffraction (XRD) showed the amorphous form of TMX inside SNEDDS. The observed hydrodynamic diameter of TMX-PAP-HA-ss-LCA SNEDDS was 367.5 nm. Furthermore, Hyaluronic Acid-based Mucoadhesive Self Nanoemulsifying Drug Delivery System (SNEDDS) of TMX showed homogeneity in synthesis with low polydispersity and negative zeta potential due to stabilization with PAP-HA-ss-LCA polymer. The distinct spherical shape of the nanodroplets was evident by transmission electron microscopy (TEM). In vitro release kinetics indicated approximately >80% release within 48 h under sink conditions. Ex-vivo permeation study displayed 7.11-folds higher permeation of TMX by TMX-PAP-HA-ss-LCA in contrast to pure TMX. The biocompatibility study proved that SNEDDS formulation was safe and compatible against macrophages. In vitro cytotoxicity studies demonstrated that TMX-PAP-HA-ss-LCA SNEDDS could efficiently kill MCF-7 breast cancer cells as compared to the native TMX drug. Systemic toxicity studies proved the non-toxic nature of TMX-PAP-HA-ss-LCA in contrast to pure TMX. Based on these evidences, TMX-PAP-HA-ss-LCA SNEDDS formulation seems to be promising mucopermeating, augmented intracellular uptake with strong targeting potential for anti-proliferative activity.

An Electrochemical Immunosensor Based on a Self-Assembled Monolayer Modified Electrode for Label-Free Detection of α-Synuclein.

This research demonstrated the development of a simple, cost-effective, and label-free immunosensor for the detection of α-synuclein (α-Syn) based on a cystamine (CYS) self-assembled monolayer (SAM) decorated fluorine-doped tin oxide (FTO) electrode. CYS-SAM was formed onto the FTO electrode by the adsorption of CYS molecules through the head sulfur groups. The free amine (-NH2) groups at the tail of the CYS-SAM enabled the immobilization of anti-α-Syn-antibody, which concurrently allowed the formation of immunocomplex by covalent bonding with α-Syn-antigen. The variation of the concentrations of the attached α-Syn at the immunosensor probe induced the alternation of the current and the charge transfer resistance (Rct) for the redox response of [Fe(CN)6]3-/4-, which displayed a linear dynamic range from 10 to 1000 ng/mL with a low detection limit (S/N = 3) of ca. 3.62 and 1.13 ng/mL in differential pulse voltammetry (DPV) and electrochemical impedance spectra (EIS) measurements, respectively. The immunosensor displayed good reproducibility, anti-interference ability, and good recoveries of α-Syn detection in diluted human serum samples. The proposed immunosensor is a promising platform to detect α-Syn for the early diagnose of Parkinson's disease, which can be extended for the determination of other biologically important biomarkers.

Disulfide-cleavage- and pH-triggered drug delivery based on a vesicle structured amphiphilic self-assembly.

Hydrophilic poly (acrylic acid) (PAA) and hydrophobic α-tocopherol succinate (TOS) were integrated via a two-step amidation with cystamine (Cys) as the linkage, and then the self-assembly of amphiphilic PAA-cys-TOS occurred in the aqueous solution of methotrexate (MTX), an anti-cancer drug, resulting a vesicle structured drug carrier. Since the disulfide (-S-S-) bridge of Cys is sensitive to glutathione (GSH) and the amide bonds in PAA-cys-TOS are sensitive to pH, disulfide-cleavage- and pH-triggered drug delivery was achieved with the amphiphilic self-assembly. Of particular interest was that the topography of the self-assembly varied remarkably during the triggered delivery, which was indicated by TEM results.

Bioimaging Applications of Carbon dots (C. dots) and its Cystamine Functionalization for the Sensitive Detection of Cr(VI) in Aqueous Samples.

In this study, one step hydrothermal synthetic strategy was adopted for preparing carbon dots (C. dots) from jeera (Cumin: Cuminum cyminum), a naturally abundant and cost effective carbon source. The physical, optical and surface functional properties of C. dots were extensively studied by different techniques such as Transmission electron microscopy (TEM), Scanning electron microscopy (SEM), spectrophotometry, fluorescence spectroscopy, Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The obtained C. dots were highly water dispersible and photostable with a quantum yield of 5.33%. The antioxidant property of C. dots was investigated by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay. The C. dots were then capped with cystamine using 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide (EDC) and N-Hydroxysuccinimide (NHS) coupling chemistry to design a selective sensing system for chromium (VI) (Cr (VI)). The minimum detection limit of Cr (VI) was found to be 1.57 µM. Biocompatibility and low toxicity of C. dots obtained from jeera made it a potential tool for bioimaging application. The internalisation of C. dots by MCF-7 breast cancer cells and Multi Drug Resistant (MDR) pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa were proved by the bioimaging of respective cells.

Covalently modified carboxyl side chains on cell surface leads to a novel method toward topology analysis of transmembrane proteins.

The research on transmembrane proteins (TMPs) is quite widespread due to their biological importance. Unfortunately, only a little amount of structural data is available of TMPs. Since technical difficulties arise during their high-resolution structure determination, bioinformatics and other experimental approaches are widely used to characterize their low-resolution structure, namely topology. Experimental and computational methods alone are still limited to determine TMP topology, but their combination becomes significant for the production of reliable structural data. By applying amino acid specific membrane-impermeable labelling agents, it is possible to identify the accessible surface of TMPs. Depending on the residue-specific modifications, new extracellular topology data is gathered, allowing the identification of more extracellular segments for TMPs. A new method has been developed for the experimental analysis of TMPs: covalent modification of the carboxyl groups on the accessible cell surface, followed by the isolation and digestion of these proteins. The labelled peptide fragments and their exact modification sites are identified by nanoLC-MS/MS. The determined peptides are mapped to the primary sequences of TMPs and the labelled sites are utilised as extracellular constraints in topology predictions that contribute to the refined low-resolution structure data of these proteins.

Benextramine and derivatives as novel human monoamine oxidases inhibitors: an integrated approach.

The two human monoamine oxidase isoforms (namely MAO A and MAO B) are enzymes involved in the catabolism of monoamines, including neurotransmitters, and for this reason are well-known and attractive pharmacological targets in neuropsychiatric and neurodegenerative diseases, for which novel pharmacological approaches are necessary. Benextramine is a tetraamine disulfide mainly known as irreversible α-adrenergic antagonist, but able to hit additional targets involved in neurodegeneration. As the molecular structures of monoamine oxidases contain nine cysteine residues, the aim of this study was to evaluate benextramine and eleven structurally related polyamine disulfides as potential MAO inhibitors. Most of the compounds were found to induce irreversible inactivation of MAOs with inactivation potency depending on both the polyamine structure and the enzyme isoform. The more effective compounds generally showed preference for MAO B. Structure-activity relationships studies revealed the key role played by the disulfide core of these molecules in the inactivation mechanism. Docking experiments pointed to Cys323, in MAO A, and Cys172, in MAO B, as target of this type of inhibitors thus suggesting that their covalent binding inside the MAO active site sterically impedes the entrance of substrate towards the FAD cofactor. The effectiveness of benextramine in inactivating MAOs was demonstrated in SH-SY5Y neuroblastoma cell line. These results demonstrated for the first time that benextramine and its derivatives can inactivate human MAOs exploiting a mechanism different from that of the classical MAO inhibitors and could be a starting point for the development of pharmacological tools in neurodegenerative diseases.

One pot preparation of magnetic chitosan-cystamine composites for selective recovery of Au(III) from the aqueous solution.

A novel magnetic chitosan adsorbent (CDF-CS) was synthesized by inserting magnetic particles into the crosslinked compound of chitosan (CS) and cystamine based on one-step method for selectively recovering Au(III) from aqueous solution. The characterization and adsorption mechanism of CDF-CS were studied by SEM-EDS, VSM, FT-IR and XPS, respectively. The experimental results show that the adsorption capacity of CDF-CS is still large in a wide range of pH values (from 1 to 7) and has a higher adsorption capacity for Au(III) than the raw chitosan, the maximum adsorption capacity of CDF-CS for Au(III) was 478.47 mg/g about 6 h at pH = 7.0. The adsorption behavior is most consistent with this pseudo-second-order kinetic model. The adsorption process of gold ions by CDF-CS follows the Langmuir adsorption isotherm. Furthermore, the thermodynamic parameter indicates that the adsorption reaction of gold ions by CDF-CS is an endothermic chemisorption. CDF-CS has great potential for removing gold ions from aqueous solutions due to the excellent repeatability and selectivity. Finally, the adsorption mechanism is that chelation reaction and ion exchange mainly occurred between CDF-CS and Au(III). Therefore, CDF-CS is very promising in recovery of Au(III) from aqueous solutions.

A multifunctional supramolecular vesicle based on complex of cystamine dihydrochloride capped pillar[5]arene and galactose derivative for targeted drug delivery.

Background: Supramolecular vesicles are a novel class of nanocarriers that have great potential in biomedicine.Methods: A multifunctional supramolecular vesicle (CAAP5G) based on the complex of CAAP5 and galactose derivative (G) assembled via host-guest interaction was constructed. Results: Using Human embryonic kidney T (293T) cells as experimental models, the cytotoxic effects of CAAP5G was investigated to 0-50 µmol/L for 24 h. Notably, the CAAP5G vesicles revealed low-toxicity to 293T cells, it was critical to designing drug nano-carriers. Simultaneously, we have evaluated doxorubicin hydrochloride (DOX)-loaded CAAP5G vesicles anticancer efficiency, where DOX-loaded CAAP5G vesicles and free DOX incubated with Human hepatocellular carcinoma cancer cell (HpeG2 cells) and 293T cells for 24 h, 48 h, 72 h. It turned out that CAAP5G vesicles encapsulated anticancer drug (DOX) could decrease DOX side-effect on 293T cells and increase DOX anticancer efficiency. More importantly, the cysteamine as an adjuvant chemotherapy drug was released from CAAP5G vesicles in HepG2 cells where a higher GSH concentration exists. The adjuvant chemotherapy efficiency was evaluated, where free DOX and DOX-loaded CAAP5G vesicles incubated with DOX-resistance HepG2 cells (HepG2-ADR cells) for 24, 48, 72 h, respectively. Conclusion: The results revealed that the DOX encapsulated by CAAP5G vesicles could enhance the cytotoxicity of DOX and provide insights for designing advanced nano-carriers toward adjuvant chemotherapies.

Base-Sequence-Independent Efficient Redox Switching of Self-Assembled DNA Nanocages.

Stimuli responsivity has been extensively pursued in dynamic DNA nanotechnology, due to its incredible application potentials. Among diverse dynamic systems, redox-responsive DNA assembly holds great promise for broad applications, especially considering that redox processes widely exist in various physiological environments. However, only a few studies have been reported on redox-sensitive dynamic DNA assembly. Albeit ingenious, most of these studies are either dependent on the DNA sequence or involve chemical modification. Herein, a facile and universal mechanism to realize redox-responsive self-assembly of DNA nanocages (tetrahedron and cube) driven by the interconversion between cystamine and cysteamine toward dynamic DNA nanotechnology is reported.

Formation of enzymatic/redox-switching nanogates on mesoporous silica nanoparticles for anticancer drug delivery.

In this study, we demonstrate a simple approach to developing mesoporous nanohybrids via a process of pre-loading of an anticancer drug (doxorubicin, DOX) into mesoporous silica nanoparticles (MSN), followed by assembly with a kind of naturally-derived polymer (gelatin, cleavable by matrix metalloproteinase 2 overexpressed by tumor). The gelatin shell is then in situ crosslinked by degradable N,N'-bis(acryloyl)cystamine (BAC) to form enzymatic and redox switchable nanogates on the mesoporous nanoparticles. The nanohybrids displayed pH/redox/enzymatic sensitivity in DOX release under conditions mimicking tumor microenvironments. The nanocarriers can be effectively taken up by A549 cells (a carcinomic human alveolar basal epithelial cell line), resulting in a high DOX intracellular accumulation and an improved anticancer cytotoxicity when compared with free DOX, suggesting their potential as a nanoplatform for therapeutic delivery.