High Concentration Of Glutathione Research Articles

Galectin-13/placental protein 13: redox-active disulfides as switches for regulating structure, function and cellular distribution.

Galectin-13 (Gal-13) plays numerous roles in regulating the relationship between maternal and fetal tissues. Low expression levels or mutations of the lectin can result in pre-eclampsia. The previous crystal structure and gel filtration data show that Gal-13 dimerizes via formation of two disulfide bonds formed by Cys136 and Cys138. In the present study, we mutated them to serine (C136S, C138S and C136S/C138S), crystalized the variants and solved their crystal structures. All variants crystallized as monomers. In the C136S structure, Cys138 formed a disulfide bond with Cys19, indicating that Cys19 is important for regulation of reversible disulfide bond formation in this lectin. Hemagglutination assays demonstrated that all variants are inactive at inducing erythrocyte agglutination, even though gel filtration profiles indicate that C136S and C138S could still form dimers, suggesting that these dimers do not exhibit the same activity as wild-type (WT) Gal-13. In HeLa cells, the three variants were found to be distributed the same as with WT Gal-13. However, a Gal-13 variant (delT221) truncated at T221 could not be transported into the nucleus, possibly explaining why women having this variant get pre-eclampsia. Considering the normally high concentration of glutathione in cells, WT Gal-13 should exist mostly as a monomer in cytoplasm, consistent with the monomeric variant C136S/C138S, which has a similar ability to interact with HOXA1 as WT Gal-13.

Investigation on vitamin e succinate based intelligent hyaluronic acid micelles for overcoming drug resistance and enhancing anticancer efficacy

Multidrug resistance (MDR) is a major reason for anticancer chemotherapy failure, and P-glycoprotein (P-gp) over-expressing on tumor cells is considered as the important target to overcome MDR. Emerging reports have showed that vitamin E (VE) can cause significant reversal of MDR due to inhibition of ATPase activity. Accordingly, we synthesized hyaluronic acid (HA) conjugated vitamin E succinate (VES) polymer, which can self-assemble into micelles and thus achieve high drug (paclitaxel (PTX) used as model drug) encapsulation as well as tumor accumulation owing to the enhanced permeability and retention (EPR) effect and HA active targeting ability. In addition, the linker between HA and VES utilized in this work was disulfide bond with reduction-sensitive property, which would respond to high glutathione (GSH) concentration in tumor cytoplasmic environment and trigger HA-CYS-VES polymer disassociation and drug release. In vitro, PTX loaded HA-CYS-VES demonstrated enhanced cytotoxicity, high apoptosis-inducing activities and reversal effects of PTX on MCF-7/Adr cells, compared to PTX. Also, cellular uptake and intracellular PTX accumulation tests displayed that PTX loaded HA-CYS-VES could more efficiently enter tumor cells and selectively release drug in cytosol so as to facilitate its function on microtubule. More importantly, PTX loaded HA-CYS-VES showed better tumor targeting ability, improved antitumor efficacy and low adverse effects on tumor-bearing mice. In conclusion, PTX loaded HA-CYS-VES exhibited a great potential for reversing MDR in anticancer chemotherapeutics.

Effect of Juice and Extracts from Saposhnikovia divaricata Root on the Colon Cancer Cells Caco-2

Colorectal cancer ranks 3rd in terms of cancer incidence. Growth and development of colon cancer cells may be affected by juice and extracts from Saposhnikovia divaricata root. The objective of the research was to analyze the effect of S. divaricata juice and extracts on the viability, membrane integrity and types of cell death of Caco-2 cells. Juice and extracts were analyzed using Ultra-High Performance Liquid Chromatography-Mass Spectrometry (UHPLC-MS) and in respect of the presence of antioxidants, total carbohydrates, protein, fat and polyphenols. The contents of cimifugin β-D-glucopyranoside, cimifugin, 4′-O-glucopyranosyl-5-O-methylvisamminol, imperatorin and protein were the highest in juice. 50% Hydroethanolic extract had the greatest antioxidant potential, concentration of polyphenols and fat. Water extract was characterized by the highest content of glutathione. Juice and 75% hydroethanolic extract contained the most carbohydrates. After the application of juice, 50% extract and the juice fraction containing the molecules with molecular weights >50 kDa, a decrease of the cell viability was noted. Juice and this extract exhibited the protective properties in relation to the cell membranes and they induced apoptosis. The knowledge of further mechanisms of anticancer activity of the examined products will allow to consider their use as part of combination therapy.

Smart Unimolecular Micelle-Based Polyprodrug with Dual-Redox Stimuli Response for Tumor Microenvironment: Enhanced in Vivo Delivery Efficiency and Tumor Penetration.

Low delivery efficiency and limited tumor penetration of nanoparticle-based drug delivery systems (DDSs), the two most concerned issues in tumor therapy, have been considered as the "Achilles' heel" for tumor treatment. In this study, we have designed a highly sensitive dual-redox-responsive prodrug-based starlike polymer β-CD-b-P(CPTGSH-co-CPTROS-co-OEGMA) (CPGR) for synergistic chemotherapy. The high glutathione (GSH) concentration and high reactive oxygen species (ROS) levels are in a dynamic equilibrium in the tumor microenvironment (TME) and could trigger the disintegration of CPGR micelles, which can promote the release of anticancer drug camptothecin (CPT) completely and intelligently. In order to verify the synergistic antitumor mechanism, two corresponding single-responsive β-CD-b-P(CPTGSH-co-OEGMA) (CPG) and β-CD-b-P(CPTROS-co-OEGMA) (CPR) were altogether prepared as contrast. Both in vitro and in vivo studies confirmed the enhanced anticancer activity of CPGR micelles in comparison of single responsive micelles. This work contributes to the orchestrated design of dual-redox-responsive DDSs for synergetic antitumor chemotherapy, which provides a good approach for the development of dual-redox-responsive nanomedicine.

Endothelial-Mesenchymal Transition Drives Expression of CD44 Variant and xCT in Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) pathogenesis shares similarities with carcinogenesis. One CD44 variant (CD44v) isoform, CD44v8-10, binds to and stabilizes the cystine transporter subunit (xCT), producing reduced glutathione and thereby enhancing the antioxidant defense of cancer stem cells. Pharmacological inhibition of xCT by sulfasalazine suppresses tumor growth, survival, and resistance to chemotherapy. We investigated whether the CD44v-xCT axis contributes to PAH pathogenesis. CD44v was predominantly expressed on endothelial-to-mesenchymal transition (EndMT)-like cells in the neointimal layer of PAH affected pulmonary arterioles. In vitro, CD44 standard form and CD44v were induced as a result of EndMT. Among human pulmonary artery endothelial cells that have undergone EndMT, CD44v+ cells showed high levels of xCT expression on their cell surfaces and high concentrations of glutathione for survival. This made CD44v+ cells the most vulnerable target for sulfasalazine. CD44v+xCThi cells showed the highest expression levels of proinflammatory cytokines, antioxidant enzymes, antiapoptotic molecules, and cyclin-dependent kinase inhibitors. In the Sugen5416/hypoxia mouse model, CD44v+ cells were present in the thickened pulmonary vascular wall. The administration of sulfasalazine started either at the same time as "Sugen5416" administration (a prevention model) or after the development of pulmonary hypertension (a reversal model) attenuated the muscularization of the pulmonary vessels, decreased the expression of markers of inflammation, and reduced the right ventricular systolic pressure, while reducing CD44v+ cells. In conclusion, CD44v+xCThi cells appear during EndMT and in pulmonary hypertension tissues. Sulfasalazine is expected to be a novel therapeutic agent for PAH, most likely targeting EndMT-derived CD44v+xCThi cells.

Programmed Release of Dihydroartemisinin for Synergistic Cancer Therapy Using a CaCO3 Mineralized Metal-Organic Framework.

Dihydroartemisinin (DHA) has attracted increasing attention as an anticancer agent. However, using DHA to treat cancer usually depends on the synergistic effects of exogenous components, and the loss of DHA during delivery reduces its effectiveness in cancer therapy. Reported herein is a programmed release nanoplatform of DHA to synergistically treat cancer with a Fe-TCPP [(4,4,4,4-(porphine-5,10,15,20-tetrayl) tetrakis(benzoic acid)] NMOF (nanoscale MOF) having a CaCO3 mineralized coating, which prevents DHA leakage during transport in the bloodstream. When the nanoplatform arrives at the tumor site, the weakly acidic microenvironment and high concentration of glutathione (GSH) trigger DHA release and TCPP activation, enabling the synergistic Fe2+ -DHA-mediated chemodynamic therapy, Ca2+ -DHA-mediated oncosis therapy, and TCPP-mediated photodynamic therapy. In vivo experiments demonstrated that the nanoplatform showed enhanced anticancer efficiency and negligible toxicity.

Multifunctional hyaluronic acid-mediated quantum dots for targeted intracellular protein delivery and real-time fluorescence imaging

The use of multifunctional quantum dots (QDs) as smart nanocarriers has exhibited substantial promise for imaging, targeting and therapeutic functionalities. Here, we describe the synthesis of green-light emitting CdZnSeS/ZnS quantum dots (QDs) combined with redox-sensitive hyaluronic acid ligand (hyaluronic acid-disulfide-linked poly(ethylene glycol)-histamine-diethylenetriamine, HA-PEG(SS)-His-Diet) for the targeted intracellular delivery of protein drugs. The generation of HA-PEG(SS)-His-Diet-QD exhibits monodispersity with high quantum yield, negligible cytotoxicity and long-term stability at pH 7.4 and 5.5. These HA-PEG(SS)-His-Diet-QDs could effectively immobilize cytochrome C (CC) with high loading efficiency, enable target of CD44-overexpressing MCF-7 human breast tumor cells, and accelerate protein release under high intracellular glutathione concentration condition. The HA-PEG(SS)-His-Diet-QD act as a promising nanocarrier for enhanced endo/lysosomal escape, targeted delivery of proteins and real-time cellular imaging. In addition, CC-loaded-HA-PEG(SS)-His-Diet-QD could effectively induce the CD44-positive cancer cells apoptosis in vitro. Ultimately, this redox-sensitive and fluorescent QD-based nanocarrier has shown major promise for targeted intracellular protein transport.

Glutathione Induced Transformation of Partially Hollow Gold-Silver Nanocages for Cancer Diagnosis and Photothermal Therapy.

Gold-silver nanocages (GSNCs) are widely used in cancer imaging and therapy due to excellent biocompatibility, internal hollow structures, and tunable optical properties. However, their possible responses toward the tumor microenvironment are still not well understood. In this study, it is demonstrated that a kind of relatively small sized (35 nm) and partially hollow GSNCs (absorbance centered at 532 nm) can enhance the intrinsic photoacoustic imaging performances for blood vessels around tumor sites. More importantly, the high concentration of glutathione around the tumor cells' microenvironment may induce the aggregation, disintegration, and agglomeration of these GSNCs sequentially, allowing significant shifts in the absorbance spectrum of GSNCs to the near-infrared (NIR) region. This enhanced absorbance in the NIR region entails the significant photothermal therapy (PTT) effect. In vivo experiments, including photoacoustic microscopy (PAM) for cancer diagnosis and PTT in tumor model mice, also show coincident consequences. Taken together, the slightly hollow GSNCs may assist PAM-based tumor diagnosis and induce a tumor targeted PTT effect. This work paves a new avenue for the development of an alternative tumor diagnostic and therapeutic strategy.

Glutathione-mediated biotransformation in the liver modulates nanoparticle transport.

Glutathione-mediated biotransformation in the liver is a well-known detoxification process to eliminate small xenobiotics but its impacts on nanoparticle retention, targeting and clearance are much less understood than liver macrophage uptake even though both processes are involved in the liver detoxification. By designing a thiol-activatable fluorescent gold nanoprobe that can bind to serum protein and be transported to the liver, we noninvasively imaged this biotransformation kinetics in vivo at high specificity and examined this process at the chemical level. Our results show that glutathione efflux from hepatocytes resulted in high local concentrations of both glutathione and cysteine in liver sinusoids, which transformed the nanoparticle surface chemistry, reduced its affinity to serum protein and significantly altered its blood retention, targeting and clearance. With this biotransformation, liver detoxification, a long-standing barrier in nanomedicine translation, can be turned into a bridge toward maximizing targeting and minimizing nanotoxicity.

Tumor-targeted biodegradable multifunctional nanoparticles for cancer theranostics

Mesoporous silica nanoparticles (MSN) attract extensive attention in area of cancer diagnosis and therapy because of their controllable nanostructures, easy surface modification and stable synthesis methods. However, their biodegradability was still controversial. This work explored the degradation effect of a type of biodegradable MSN (bMSN) in different environments and simultaneously endowed it with imaging functions and high-efficiency targeting effect on cancer cell, thus forming a multifunctional biodegradable drug carrier (bMSN-ss-GABA) for cancer theranostics. The bovine serum albumin-based Gd/Au complex (BSA-Gd/Au) was wrapped on the surface of bMSN through disulfide linkage, acting as contrast agent for magnetic resonance (MR) and fluorescence imaging, and then folate (FA), whose receptor (FR) is overexpressed in KB human oral epidermoid carcinoma cells, was modified on the nanocarriers as a targeting ligand. TEM revealed the degradation process of bMSN and a series of characterization methods verified the successful construction of bMSN-ss-GABA. Doxorubicin hydrochloride (DOX) loaded bMSN-ss-GABA (DOX@bMSN-ss-GABA) was proved with redox-responsiveness, thereby triggering rapid drug release under specific tumor microenvironment of high glutathione concentration. Further, the excellent imaging capability was also fully inspected. What’s more, the results of endocytosis and tumor growth inhibition of DOX@bMSN-ss-GABA demonstrated the highly effective targeting effect of hybird nanocarriers. Therefore, the prepared DOX@bMSN-ss-GABA might be used as a promising nanotheranostic agent for KB human oral epidermoid carcinoma.

Tunable environmental sensitivity and degradability of nanogels based on derivatives of cystine and poly(ethylene glycols) of various length for biocompatible drug carrier

Nanogels are promising carriers for drug delivery, especially when they degrade under conditions typical for cancer cells to release a drug. By using the precipitation polymerization we synthesized a biocompatible and degradable nanogel based on poly(ethylene glycol) methyl ether methacrylate (OEGMA) and di(ethylene glycol) methyl ether methacrylate (MEO2MA) cross-linked with a redox-sensitive linker, N,N′-bis(methacryloyl)cystine – (mBISS). The application of appropriate proportions of monomers during the nanogel synthesis allowed us to set its volume-phase-transition temperature to the body temperature while the aggregation of the nanogel in physiological conditions was eliminated. The presence of carboxylic groups in mBISS made the nanogel sensitive to pH, gave it stability under conditions of high ionic strength and allowed it to bind the anticancer drug – doxorubicin (DOX). The degradation of nanogel was examined by using electron microscopies. In the presence of a high concentration of glutathione (a reducing agent for the -S-S- bridges) which is the case for most cancer cells, the spherical shape of the nanogel and correspondingly its structure were destroyed. The obtained profiles for the release of DOX from the nanogel revealed that the smallest amount of DOX was released from the nanogel at pH 7.4, while under conditions present in most cancer cells, this is at pH 5.0 and cGSH = 40 mM, the highest cumulative release of DOX was observed. The DOX loaded nanogels were cytotoxic against MCF-27 and HT-29 cancer cells similarly to DOX alone. The unloaded gel nanoparticles did not inhibit proliferation of the cells.

MiRNA Delivery System Based on Stimuli-Responsive Gold Nanoparticle Aggregates for Multimodal Tumor Therapy.

In this work, a composite of microRNA-124-5p mimics (miR-124-5p) and gold nanoparticle (AuNP) aggregates was fabricated to combine the gene therapy and photothermal therapy for effective tumor medicine. The AuNP aggregates cross-linked by cystamine not only serve as photothermal therapeutic agents but are able to condense miR-124-5p as nanocarrier for gene delivery because of the coulomb interaction. The release of miR-124-5p could be initiated by the cleavage of cystamine when the nanocarrier enter the cytoplasm of tumor cells through endocytosis, where contains high concentration of glutathione (GSH). Moreover, the size of the AuNP aggregates did not change after the GSH-triggered miR-124-5p release because of the coinstantaneous disruption of disulfide bond and reformation of the thiol-gold bond, resulting in sustained photothermal property of the nanocarrier for tumor therapy. In vitro experiments showed that the miRNA@AuNAs (miR-124-5p) composite under near-infrared radiation performed great cytotoxicity to tumor cells, which is two and three times higher than the group of pure AuNP aggregates under near-infrared radiation and miRNA@AuNAs composite without near-infrared radiation, respectively. All experiment statistics show that the miRNA@AuNAs composite with combination of photothermal therapy and gene therapy has great potential for effective tumor treatment.

Glutathione from Saccharomyces cerevisiae as By-Product of Second Generation Bioethanol from Oil Palm of Empty Fruit Bunch Fiber

Glutathione is an antioxidant agent can be applied in various fields such as pharmacy, cosmetic, foodstuff and another field. The objective of this research is to obtained glutathione from Saccharomyces cerevisiae in fermentation waste as by product of second generation of bioethanol (G2). After bioethanol process for 72h, centrifuge method was used to separate the yeast cells from residual fermentation broth of bioethanol. The yeast cells were extracted by maceration method using variation solvent with 25% ethanol solvent, 40% ethanol in water, H3PO4 0.1 M and Phosphate Buffer pH 7.2. Glutathione concentration was tested with alloxan method using Spectrophotometer UV-Vis and characterization using LC-MS. The result showed fermentation of oil palm empty fruit bunch (OPEFB)15% obtained ethanol 39 g/L and total cell after 72 h showed 2.15 x 108. The highest glutathione concentration had obtained from phosphate buffer pH 7.2 with extraction time 90 min which is equal 1449.52 mg/L.

Bovine serum albumin-templated nanoplatform for magnetic resonance imaging-guided chemodynamic therapy

BackgroundNanotechnology in medicine has greatly expanded the therapeutic strategy that may be explored for cancer treatment by exploiting the specific tumor microenvironment such as mild acidity, high glutathione (GSH) concentration and overproduced hydrogen peroxide (H2O2). Among them, tumor microenvironment responsive chemodynamic therapy (CDT) utilized the Fenton or Fenton-like reaction to produce excess hydroxyl radical (·OH) for the destruction of tumor cells. However, the produced ·OH is easily depleted by the excess GSH in tumors, which would undoubtedly impair the CDT’s efficiency. To overcome this obstacle and enhance the treatment efficiency, we design the nanoplatforms for magnetic resonance imaging (MRI)-guided CDT.ResultsIn this study, we applied the bovine serum albumin (BSA)-templated CuS:Gd nanoparticles (CuS:Gd NPs) for MRI-guided CDT. The Cu2+ in the CuS:Gd NPs could be reduced to Cu+ by GSH in tumors, which further reacted with H2O2 and triggered Fenton-like reaction to simultaneously generate abundant ·OH and deplete GSH for tumor enhanced CDT. Besides, the Gd3+ in CuS:Gd NPs endowed them with excellent MRI capability, which could be used to locate the tumor site and monitor the therapy process preliminarily.ConclusionsThe designed nanoplatforms offer a major step forward in CDT for effective treatment of tumors guided by MRI.

Nanoscale Metal-Organic-Frameworks Coated by Biodegradable Organosilica for pH and Redox Dual Responsive Drug Release and High-Performance Anticancer Therapy.

Responsive nanocarriers with biocompatibility and precise drug releasing capability have emerged as a prospective candidate for anticancer treatment. However, the challenges imposed by the complicated preparation process and limited loading capacities have seriously impeded the development of novel multifunctional drug delivery systems. Here, we developed a novel and dual-responsive nanocarrier based on a nanoscale ZIF-8 core and an organosilica shell containing disulfide bridges in its frameworks through a facile and efficient strategy. The prepared ZIF-8@DOX@organosilica nanoparticles (ZDOS NPs) exhibited a well-defined structure and excellent doxorubicin (DOX) loading capability (41.2%) with pH and redox dual-sensitive release properties. The degradation of the organosilica shell was observed after 12 h incubation with a 10 mM reducing agent. Confocal imaging and flow cytometry analysis further proved that the nanocarriers can efficiently enter cells and complete intracellular DOX release under the low pH and high glutathione concentrations, which resulted in an enhanced cytotoxicity of DOX for cancer cells. Meanwhile, subcellular localization experiments revealed that the ZDOS NPs entered cells mainly by endocytosis and then escaped from lysosomes into the cytosol. Moreover, in vivo assays also demonstrated that the ZDOS NPs exhibited negligible systemic toxicity and significantly enhanced anticancer efficiencies compared with free DOX. In summary, our prepared pH and redox dual-responsive nanocarriers provide a potential platform for controlled release and cancer treatment.

Glutathione-Induced Structural Transform of Double-Cross-Linked PEGylated Nanogel for Efficient Intracellular Anticancer Drug Delivery.

A glutathione-sensitive poly[methacrylic acid- co-poly(ethylene glycol) methyl ether methacrylate] (PMAABACy- co-PEGMA) nanogel with tunable stability has been fabricated through covalent and metal double-cross-linking strategies in response to the differential change of GSH concentration between the inside and outside of tumor cells. Herein, the size-controlled PMAA- co-PEGMA that possessed unique core-shell structure was first obtained via adjusting the length of PEGMA. Furthermore, N, N-bis(acryloyl)cystamine was introduced to endow PMAA- co-PEGMA with glutathione-sensitive property. The PMAABACy- co-PEGMA950 nanogel exhibited reasonable particle size and desired hydrodynamic diameter that was further cross-linked by Fe(III) ions to obtain a double-cross-linked PMAABACy/Fe(III)- co-PEGMA950 vehicle. In this double-cross-linked vehicle, the existence of metal cross-linked structure made this vehicle possess favorable structural stability to restrict the premature leakage of therapeutic drug. The introduction of covalent cross-linked structure synchronously imparted the vehicle with glutathione-sensitive property in response to the high intracellular glutathione concentrations in tumor cells to induce its structural transform for realizing the release of drug. Additionally, a series of in vitro evaluations demonstrated that PMAABACy/Fe(III)- co-PEGMA950 displayed remarkable biocompatibility and glutathione-sensitive release toward anticancer drug in the simulated intracellular environment of tumor tissues. Notably, the drug-loaded PMAABACy/Fe(III)- co-PEGMA950 exhibited excellent anticancer activity against tumor cells. The double-cross-linked PMAABACy/Fe(III)- co-PEGMA950 nanogel therefore is expected to be a promising tumor microenvironment-sensitive platform for delivering chemotherapeutic drugs.

Dual pH/Redox-Responsive Mixed Polymeric Micelles for Anticancer Drug Delivery and Controlled Release.

Stimuli-responsive polymeric micelles (PMs) have shown great potential in drug delivery and controlled release in cancer chemotherapy. Herein, inspired by the features of the tumor microenvironment, we developed dual pH/redox-responsive mixed PMs which are self-assembled from two kinds of amphiphilic diblock copolymers (poly(ethylene glycol) methyl ether-b-poly(β-amino esters) (mPEG-b-PAE) and poly(ethylene glycol) methyl ether-grafted disulfide-poly(β-amino esters) (PAE-ss-mPEG)) for anticancer drug delivery and controlled release. The co-micellization of two copolymers is evaluated by measurement of critical micelle concentration (CMC) values at different ratios of the two copolymers. The pH/redox-responsiveness of PMs is thoroughly investigated by measurement of base dissociation constant (pKb) value, particle size, and zeta-potential in different conditions. The PMs can encapsulate doxorubicin (DOX) efficiently, with high drug-loading efficacy. The DOX was released due to the swelling and disassembly of nanoparticles triggered by low pH and high glutathione (GSH) concentrations in tumor cells. The in vitro results demonstrated that drug release rate and cumulative release are obviously dependent on pH values and reducing agents. Furthermore, the cytotoxicity test showed that the mixed PMs have negligible toxicity, whereas the DOX-loaded mixed PMs exhibit high cytotoxicity for HepG2 cells. Therefore, the results demonstrate that the dual pH/redox-responsive PMs self-assembled from PAE-based diblock copolymers could be potential anticancer drug delivery carriers with pH/redox-triggered drug release, and the fabrication of stimuli-responsive mixed PMs could be an efficient strategy for preparation of intelligent drug delivery platform for disease therapy.

Biodegradable hybrid mesoporous silica nanoparticles for gene/chemo-synergetic therapy of breast cancer.

Mesoporous silica nanoparticles have been extensively explored in anticancer nanomedicine due to their excellent biodegradability, which is one important focus in their further clinical translations. However, the traditional design concepts based on the functional modification with active groups cannot significantly improve the controlled drug release efficiency and anticancer effect. Herein, a molecularly organic-inorganic hybrid mesoporous silica nanoparticle (HMSN) nanocarrier coated with hyaluronic acid (HA) and polyethyleneimine (PEI) was constructed for the gene/chemo-synergetic therapy of breast cancer. Notably, HMSN with tumor-sensitive disulfide bond and targeting ligand HA can be decomposed when it encounters high concentration of glutathione (GSH) and hyaluronidase (HAase). The biodegradability of host molecules and the fast disintegration of the framework in tumor microenvironment can also accelerate the stimuli responsive release of cargos inside the pore space. Furthermore, the grafting of polyethyleneimine (PEI) could increase gene loading efficiency. From the above, the smart approach involves a combination of biodegradability and biological effect and results in synergetic antitumor effect of gene and chemical drug on breast cancer. All these findings demonstrated that HMSN/HA/PEI nanocarriers can be suitable for biomedical application, paving the way to fast development of multi-functional nano-biomedicine.

Synthesis and characterisation of functional manganese doped ZnS quantum dots for bio-imaging application

ABSTRACTFluorescent quantum dots (QDs) are potential candidates for bio-imaging but major problems in using them for bio-imaging applications are either bandgap lying in UV region or the cytotoxicity of the visible light-excited cadmium-based QDs. Keeping these things in mind, glutathione (GLT) functionalised Mn-doped ZnS QDs has been studied to make a desired fluorescent system for bioimaging application. XRD measurements show that grain size decreases at higher concentration of GLT capping on Mn-doped quantum dots. UV–visible studies show that the band gap shows a blue shift at higher GLT concentration. FTIR studies confirm GLT functionalisation on the surface of ZnS QDs. Both UV excited and IR excited photoluminescence spectrum of samples exhibited a tunable orange emission intensity with increase in GLT concentration however multiphoton infrared excited spectra was used to show the feasibility of GLT functionalised ZnS:Mn quantum dots for a real application in a biological window of 650–950 nm.

Synergistically enhanced anticancer effect of codelivered curcumin and siPlk1 by stimuli-responsive α-lactalbumin nanospheres.

To achieve enhanced anticancer efficacy by combined siPlk1 and curcumin (cur) therapy using α-lactalbumin (α-lac) nanocarrier delivery. α-Lac was partially hydrolyzed into amphiphilic peptides,and then self-assembled into nanospheres(NS). Cur was loaded into their hydrophobic core during the self-assembly process. siPlk1-SH was cross-linked with the endogenous cysteines on the NS. CRGDK peptide was conjugated on NS to target integrins overexpressed in HeLa cells. The Cur and siPlk1 coloaded NS formulations possessed an enhanced tumor targeting and antitumor properties. Drugs were responsively released from disulfide bonds cross-linked RGD-NS/Cur/siPlk1corresponding to the high intracellular glutathione concentrations of cancer cells. Both in vitro cell viability experiments and in vivo antitumor evaluations demonstrated that the codelivered nanosphere platform exhibited excellent tumor targeting and synergistic antitumor efficacy.