Characterization and functional analysis of peroxiredoxin 4 gene in the Neocaridina denticulata sinensis.

Peroxiredoxin (Prx) is an antioxidant protein family, which widely exists in organisms and plays an important role in innate immunity. In this study, the full-length cDNA of a Prx gene (NdPrx) was obtained from Neocaridina denticulata sinensis, which contains a 735 bp open reading frame (ORF) and encodes a polypeptide of 244 amino acids. It is inferred that the molecular weight of the encoded amino acid is 27261.20 Da and the theoretical isoelectric point is 6.16. Phylogenetic analysis shows that NdPrx and Prx4 have high homology, so it was named NdPrx4. Multiple alignment analysis showed that the amino acid sequence of NdPrx4 had high homology with Prx4 of other species, and the similarity with Homarus americanus was the highest, 92.86%. Quantitative real-time PCR analysis showed that NdPrx4 was expressed in various tissues of N. denticulata sinensis, and the expression in ovary was the highest. It was speculated that NdPrx4 may be related to maternal immune function. Under the stimulation of Cu2+, the expression of NdPrx4 reached the peak at 36 h, and showed a downward trend until 72 h, indicating that NdPrx4 may play an important role in the stress response of N. denticulata sinensis. Then, NdPrx4 was recombinantly expressed in E. coli, and its enzymatic characteristics of rNdPrx4 were detected. The result showed that the activity of rNdPrx4 was the highest at pH 5.0 and 55 °C. It was found that Mn2+ and Ca2+ can inhibit the activity of rNdPrx4, and Zn2+ increases the activity of rNdPrx4.

Characterization of peroxiredoxin from Neocaridina denticulata sinensis and its antioxidant and DNA protection activity analysis.

Peroxiredoxin (Prx) is an antioxidant protein that widely exists in various organisms. To further investigate the role of Prx in the antioxidant and immune responses of Neocaridina denticulata sinensis, the full-length cDNA sequence of a Prx gene (Nd-Prx) from N. denticulata sinensis was obtained. The open reading frame (ORF) of Nd-Prx is 597 bp and encodes 198 amino acids. Amino acid similarity alignment showed that Nd-Prx contained a conserved sequence region "FYPLDFTFVCPTEI". qRT-PCR assay showed that Nd-Prx was expressed in all tested tissues and its expression was highest in the ovary. Nd-Prx was most highly expressed at 36 h after copper stimulation. Nd-Prx expression levels in hepatopancreas were significantly upregulated after Vibrio parahaemolyticus challenge (P < 0.05). In addition, the recombinant Nd-Prx was prepared and its enzyme activity was most stable at 70 °C with pH of 6.0. The antioxidant activity and DNA protection of recombinant Nd-Prx was also demonstrated. In summary, this study investigated the role of Prx in antioxidant and immune responses of N. denticulata sinensis, which might provide a foundation for further exploring Prx in immune system of crustaceans and for the application in disease control.

Transcriptomic analysis of Neocaridina denticulate sinensis hepatopancreas indicates immune changes after copper exposure.

Neocaridina denticulate sinensis is a promising crustacean model species due to its merits in raising and breeding. However, its molecular responses to copper remains largely unknown. In the present research, RNA-seq was used to mine the alteration in transcriptome of N. denticulate sinensis hepatopancreas under copper exposure. A total of 16,423 DEGs was identified between control and Cu2+ treatment groups. GO enrichment analysis of all DEGs suggested down-regulated genes exceeded up-regulated genes in all the significantly enriched terms, except for RNA polymerase III complex (GO:0005666). KEGG analysis showed Cu exposure only induced two significantly enriched pathways, including Phagosome (ko04145) and Pathogenic Escherichia coli infection (ko05130). Besides, pattern recognition receptors as Toll, lectin B, CTL1 and SRB, AMPs as crustin type I, lysozyme, and NOS were down-regulated after Cu2+ exposure, while hemocyanin, MT, HSP70 and HSP90 were significantly up-regulated, implying these molecules may play vital role in Cu2+ detoxification of N. denticulate sinensis. Our results here provide research direction of heavy metal detoxification of N. denticulate sinensis, simultaneously enriched its genomic information.

PET bottles recycling in China: An LCA coupled with LCC case study of blanket production made of waste PET bottles.

A large number of polyethylene terephthalate (PET) bottles are discarded daily after usage. Thus, plastic bottle recycling has elicited considerable attention in recent years. In this context, this study aims to quantify the environmental and economic impacts of blanket production from 100% recycled waste plastic bottles in China through a life cycle assessment coupled with life cycle costing method. In addition, the environmental impact of replacing coal with natural gas and solar energy was evaluated. Results show that impact categories of global warming and fossil depletion have significant influence on the overall environment. Carbon dioxide, water, iron, coal and chromium (VI) to water are the main contributors to the overall environmental burden. The internal and external costs are $6433/metric ton and $370/metric ton, respectively. Analysis results indicate that the optimization of organic chemicals, recycled polyester filament and steam production processes can reduce environmental and economic burdens substantially. Energy substitutions with natural gas and the use of solar photovoltaic in steam production and electricity generation are effective measures for decreasing environmental impacts. Finally, suggestions based on research results and the current status of waste plastic bottle recycling in China are proposed.

Bioinspired Polydopamine-Coated Hemoglobin as Potential Oxygen Carrier with Antioxidant Properties.

Oxidative side reaction is one of the major factors hindering the development of hemoglobin-based oxygen carriers (HBOCs). To avoid the oxidative toxicity, we designed and synthesized polydopamine-coated hemoglobin (Hb-PDA) nanoparticles via simple one-step assemblage without any toxic reagent. Hb-PDA nanoparticles showed oxidative protection of Hb by inhibiting the generation of methemoglobin (MetHb) and ferryl (Fe IV) Hb, as well as excellent antioxidant properties by scavenging free radicals and reactive oxygen species (ROS). Interestingly, the scavenging rate of Hb-PDA nanoparticles for ABTS+ radical is at most 89%, while for DPPH radical it reaches 49%. In addition, Hb-PDA efficiently reduced the intracellular H2O2-induced ROS generation. Moreover, Hb-PDA nanoparticles exhibited high oxygen affinity, low effect on blood constituents, and low cytotoxicity. The results indicate that polydopamine-coated hemoglobin might be a promising approach for constructing novel oxygen carriers with the capacity to reduce oxidative side reaction.

Construction of a artificial glutathione peroxidase with temperature-dependent activity based on a supramolecular graft copolymer.

A supramolecular artificial glutathione peroxidase (PNIPAM-CD-g-Te) was prepared based on a supramolecular graft copolymer. PNIPAM-CD-g-Te was constructed by supramolecular host-guest self-assembly. Significantly, PNIPAM-CD-g-Te displayed noticeable temperature-dependent catalytic activity and typical saturation kinetics behavior. It was also proved that the change in the self-assembled structure of PNIPAM-CD-g-Te during the temperature-dependent process played a significant role in the temperature-dependent catalytic behavior. The construction of PNIPAM-CD-g-Te based on supramolecular graft copolymer endows artificial GPx with temperature-dependent catalytic ability, enriched catalytic centers, and homogeneously distributed catalytic centers. This work bodes well for the development of other biologically related host-guest supramolecular biomaterials.

Construction of a smart microgel glutathione peroxidase mimic based on supramolecular self-assembly.

In an effort to construct smart artificial glutathione peroxidase (GPx) featuring high catalytic activity in an efficient preparation process, an artificial microgel GPx (PPAM-ADA-Te) has been prepared using a supramolecular host-guest self-assembly technique. Herein, 6,6'-telluro-bis(6-deoxy-ß-cyclodextrin) (CD-Te-CD) was selected as a tellurium-containing host molecule, which also served as the crosslinker for the scaffold of the supramolecular microgel. And an adamantane-containing block copolymer (PPAM-ADA) was designed and synthesized as a guest building block copolymer. Subsequently, PPAM-ADA-Te was constructed through the self-assembly of CD-Te-CD and PPAM-ADA. The formation of this self-assembled construct was confirmed by dynamic light scattering, NMR, SEM and TEM. Notably, PPAM-ADA-Te not only exhibits a significant temperature responsive catalytic activity, but also features the characteristic saturation kinetics behaviour similar to that of a natural enzyme catalyst. We demonstrate in this paper that both the hydrophobic microenvironment and the crosslinker in this supramolecular microgel network played significant roles in enhancing and altering the temperature responsive catalytic behaviour. The successful construction of PPAM-ADA-Te not only provides a novel method for the preparation of microgel artificial GPx with high catalytic activity but also provides properties suitable for the future development of intelligent antioxidant drugs.

Distribution and exposure risk assessment of chlorinated paraffins and novel brominated flame retardants in toys.

Chlorinated paraffins (CPs) and novel brominated flame retardants (NBFRs) were examined in children's toys collected from 13 families in China. The concentrations of short-chain CPs (SCCPs), medium-chain CPs (MCCPs) and NBFRs in toys were 32.8-1,220,954 ng/g, not detected-2,688,656 ng/g and 0.08-103,461 ng/g, respectively. Median concentrations of SCCPs and MCCPs in toys were 1355 and 1984 ng/g, respectively, while except for pentabromobenzene (median:0.04 ng/g), the median concentrations of the other 8 NBFRs were below method detection limits. Rubber and foam toys contained higher amounts of CPs and NBFRs. Among the SCCPs and MCCPs monitored, Cl6-8-SCCPs/MCCPs and C14-MCCPs were the most abundant congener groups. On the other hand, decabromodiphenyl ethane was the predominant NBFR in toys. Moreover, to understand the role of toys in children's daily exposure to CPs and NBFRs, hand-to-mouth contact, mouthing, and dermal exposure were assessed for children aged 3 months to 6 years. Hand-to-mouth contact is the primary exposure route for children's exposure to CPs (25.4-536 ng/kg/day) and NBFRs (1.24-26.2 ng/kg/day) through toys. A low deleterious risk associated with children's toys concerning CPs and NBFRs was investigated based on the margin of exposure and hazard quotient values.

Molecular characterization and functional analysis of peroxiredoxin 3 (NdPrx3) from Neocaridina denticulata sinensis.

Peroxiredoxins (Prxs) widely exist in organisms and can prevent oxidative damage. Here, the characterization and biological function of NdPrx3 from Neocaridina denticulata sinensis were analyzed. The coding sequence of NdPrx3 consists of 684 bp open reading frame (ORF), encoding 227 amino acids with a predicted molecular weight of 24.7 kDa and theoretical pI 6.49. Multiple sequence alignments showed that the conserved domains of NdPrx3, including catalytic triad, dimer interface, decamer interface, peroxidatic, and resolving cysteines, were similar to those of other organisms. The phylogenetic relationship demonstrated that NdPrx3 clustered in the Prx3 class. The highest relative expression of NdPrx3 mRNA was confirmed in gill among the nine tissues from healthy shrimp. The transcript level of NdPrx3 was significantly upregulated from 0 h to 48 h and decreased in 72 h under copper challenge, indicating that NdPrx3 may play an important role in the copper challenge of N. denticulata sinensis. In addition, NdPrx3 was recombinantly expressed in E. coli and purified to one band on SDS-PAGE. The DNA protection of rNdPrx3 was verified. The enzymatic assay of the recombinant NdPrx3 indicated that it had the oxidoreductase function and was stable at a low temperature (10-30 °C).

Genome-wide identification and expression profiling of Wnt gene family in Neocaridina denticulata sinensis.

Wnt proteins are a class of hydrophobic secreted glycoproteins involved in diverse important biological processes, such as tissue formation and regeneration, embryonic development and innate immunity. The Wnt gene family has an early origin and is present in all deuterostomes. In the process of evolution, the phenomenon of gene expansion, contraction and adaptive evolution occurs in the Wnt gene family. In the current study, eleven Wnt genes (NdWnt1-2, NdWnt4-7, NdWnt9-11, NdWnt16, and NdWntA) belonging to different subfamilies were obtained based on the genomic and transcriptomic data of Neocaridina denticulata sinensis. Then the expression patterns of all NdWnts were analyzed in various tissues, at different developmental stages and under different stresses. The expression profiles of NdWnts at different developmental stages showed that most NdWnt genes were initially expressed at gastrula stage, and the expression of NdWnt5 and NdWnt16 throughout all developmental stages. The spatial expression of NdWnt genes presented tissue specificity. They were mainly expressed in four tissues, namely gill, intestines, ovary and eyestalk. After Vibrio parahemolyticus infection and under copper exposure, the expression levels of five NdWnts (NdWnt1, NdWnt5, NdWnt10, NdWnt16 and NdWntA) were variable. Our findings enrich the research on the Wnt gene family of N. denticulata sinensis and provide valuable insights into relationship between structure and function of Wnt genes in crustaceans.

Percutaneous absorption and exposure risk assessment of organophosphate esters in children's toys.

The percutaneous penetration and exposure risk of organophosphate esters (OPEs) from children's toys remains largely unknown. Percutaneous penetration of OPEs was evaluated by EPISkin™ model. Chlorinated OPEs (Cl-OPEs) and alkyl OPEs, except tris(2-ethylhexyl) phosphate, exhibited a fast absorption rate and good dermal penetration ability with cumulative absorptions of 57.6-127 % of dosed OPEs. Cumulative absorptions of OPEs through skin cells were inversely associated with their molecular weight and log octanol-water partition coefficient. Additionally, a quantitative structure-activity relationship model indicated that topological charge and steric features of OPEs were closely related to the transdermal permeability of these chemicals. With the clarification of the factors affecting the transdermal penetration of OPEs, the level and exposure risk of OPEs in actual toys were studied. The summation of 18 OPE concentrations in 199 toy samples collected from China ranged from 6.82 to 228,254 ng/g, of which Cl-OPEs presented the highest concentration. Concentrations of OPEs in toys exhibited clear type differences. Daily exposure to OPEs via dermal, hand-to-mouth contact, and mouthing was evaluated, and dermal contact was a significant route for children's exposure to OPEs. Hazard quotients for noncarcinogenic risk assessment were below 1, indicating that the health risk of OPEs via toys was relatively low.

Cyclic RGD-Decorated Liposomal Gossypol AT-101 Targeting for Enhanced Antitumor Effect.

INTRODUCTION: (-)-Gossypol (AT-101), the (-)-enantiomer of the natural compound gossypol, has shown significant inhibitory effects on various types of cancers such as osteosarcoma, myeloma, glioma, lung cancer, and prostate cancer. However, the clinical application of (-)-gossypol was often hindered by its evident side effects and the low bioavailability via oral administration, which necessitated the development of suitable (-)-gossypol preparations to settle the problems. In this study, injectable cyclic RGD (cRGD)-decorated liposome (cRGD-LP) was prepared for tumor-targeted delivery of (-)-gossypol. METHODS: The cRGD-LP was prepared based on cRGD-modified lipids. For comparison, a non-cRGD-containing liposome (LP) with a similar chemical composition to cRGD-LP was specially designed. The physicochemical properties of (-)-gossypol-loaded cRGD-LP (Gos/cRGD-LP) were investigated in terms of the drug loading efficiency, particle size, morphology, drug release, and so on. The inhibitory effect of Gos/cRGD-LP on the proliferation of tumor cells in vitro was evaluated using different cell lines. The biodistribution of cRGD-LP in vivo was investigated via the near-infrared (NIR) fluorescence imaging technique. The antitumor effect of Gos/cRGD-LP in vivo was evaluated in PC-3 tumor-bearing nude mice. RESULTS: Gos/cRGD-LP had an average particle size of about 62 nm with a narrow size distribution, drug loading efficiency of over 90%, and sustained drug release for over 96 h. The results of NIR fluorescence imaging demonstrated the enhanced tumor targeting of cRGD-LP in vivo. Moreover, Gos/cRGD-LP showed a significantly enhanced inhibitory effect on PC-3 tumors in mice, with a tumor inhibition rate of over 74% and good biocompatibility. CONCLUSION: The incorporation of cRGD could significantly enhance the tumor-targeting effect of the liposomes and improve the antitumor effect of the liposomal (-)-gossypol in vivo, which indicated the potential of Gos/cRGD-LP that warrants further investigation for clinical applications of this single-isomer drug.

A cellulose-based adsorbent with pendant groups of quaternary ammonium and amino for enhanced capture of aqueous Cr(VI).

As a promising candidate of Cr(VI) decontamination, cellulose is limited in the Cr(VI) uptake due to its poor accessibility. Herein, We describe the synthesis of a novel cellulose-based adsorbent (PQC, where P and QC designate the polyethylenimine and quaternized cellulose, respectively) with functional groups of quaternary ammonium and amino for enhanced capture of Cr(VI) from water. For preparing PQC, cellulose is first quaternized homogeneously, followed by grafting and/or cross-linking with polyethylenimine in the presence of epichlorohydrin. The PQC follows the Langmuir isotherm and presents a maximum Cr(VI) uptake capacity of 490.3 mg/g at 30 °C and initial pH about 2.0, much higher than many other reported cellulose-based adsorbents. The adsorption of PQC is spontaneous and endothermic, which follows the pseudo-second-order kinetic model and achieves the equilibrium after contacting about 50 min. Furthermore, the PQC, with favorable reusability, can work well in a high coexisting anion concentration. These excellent absorption performances are attributed to its physicochemical properties such as the robust porous structure and high density of functional groups including quaternary ammonium, amino and hydroxyl, which improve the availability to capture or reduce Cr(VI). This work demonstrates the significant potential of cellulose-based adsorbent for remediating aqueous Cr(VI).

Nucleosome-inspired nanocarrier obtains encapsulation efficiency enhancement and side effects reduction in chemotherapy by using fullerenol assembled with doxorubicin.

Chemodrugs have been widely used to treat cancer; however, the chemotherapy usually leads to serious side effects and failure. Various nanomaterials and strategies have been explored for drug delivery to improve the efficacy of chemodrugs. One key to loading chemodrugs onto a nano-delivery system is enhancement of the encapsulation efficiency, especially for polymeric nanoparticles being loaded with hydrophilic drugs. Inspired by the ability of eukaryote to package millions of genes in the nucleus wrapping and condensing DNA around histones to form chromosomes, here we developed a karyon-like hybrid nanoparticle to achieve ultra-high encapsulation of doxorubicin (Dox) with reduced side effects. We utilized fullerenol as a "histone", packaged a great number of Dox, and used PEG-PLGA as the "karyotheca" coating the "nucleosome" (fullerenol and Dox complex) to stabilize the complex. It is noteworthy that the encapsulation efficiency of Dox in the polymeric micelles was increased from ∼5% to ∼79%. What's more, the biomimetic-inspired delivery system significantly reduced the chemodrug side effects by utilizing the radical scavenging ability of fullerenol. This novel drug-delivery design approach provides useful insights for improving the applicability of fullerenol in drug delivery systems for cancer therapy.

Influence of polydopamine-mediated surface modification on oxygen-release capacity of haemoglobin-based oxygen carriers.

Oxidative toxicity has impeded the development of haemoglobin-based oxygen carriers (HBOCs) by causing methaemoglobin (MetHb) formation and inducing oxidative stress. In our previous work, polydopamine-coated haemoglobin (Hb-PDA) nanoparticles have been designed and synthesized with the capacity to reduce oxidative toxicity. In this investigation, the mass ratio of dopamine (DA) to haemoglobin (Hb) and the pH value are found to be the primary factors that influence preparation of Hb-PDA nanoparticles. X-ray photoelectron spectroscopy showed that the catechol groups of DA play a crucial role in the modification of Hb surface. Hb-PDA nanoparticles were found to exhibit oxidative protection from hydrogen peroxide (H2O2) and the change of mitochondrial membrane potential showed that the Hb-PDA nanoparticles reduced H2O2-induced apoptosis. It is demonstrated that modification of PDA could maintain the oxygen-release capacity of Hb. These findings confirm that Hb-PDA nanoparticles possess restrained oxidative toxicity and preserve oxygen-release capacity.

Mesoporous Silica Coated Polydopamine Functionalized Reduced Graphene Oxide for Synergistic Targeted Chemo-Photothermal Therapy.

The integration of different therapies into a single nanoplatform has shown great promise for synergistic tumor treatment. Herein, mesoporous silica (MS) coated polydopamine functionalized reduced graphene oxide (pRGO) further modified with hyaluronic acid (HA) (pRGO@MS-HA) has been utilized as a versatile nanoplatform for synergistic targeted chemo-photothermal therapy against cancer. A facile and green chemical method is adopted for the simultaneous reduction and noncovalent functionalization of graphene oxide (GO) by using mussel inspired dopamine (DA) to enhance biocompatibility and the photothermal effect. Then, it was coated with mesoporous silica (MS) (pRGO@MS) to enhance doxorubicin (DOX) loading and be further modified with the targeting moieties hyaluronic acid (HA). The pH-dependent and near-infrared (NIR) laser irradiation-triggered DOX release from pRGO@MS(DOX)-HA is observed, which could enhance the chemo-photothermal therapy effect. In vitro experimental results confirm that pRGO@MS(DOX)-HA exhibits good dispersibility, excellent photothermal property, remarkable tumor cell killing efficiency, and specificity to target tumor cells. In vivo antitumor experiments further demonstrated that pRGO@MS(DOX)-HA could exhibit an excellent synergistic antitumor efficacy, which is much more distinct than any monotherapy. This work presents a novel nanoplatform which could load chemotherapy drugs with high efficiency and be used as light-mediated photothermal cancer therapy agent.

Relative bioavailability and bioaccessibility of PCBs in soils based on a mouse model and Tenax-improved physiologically-based extraction test.

In this study, bioavailability of polychlorinated biphenyls (PCBs) in soil samples aged for various time intervals (7 days, 1 and 5 months) was assessed by in vivo tests using mice. The in vivo bioavailability of PCBs in soil ranged from 45% (PCB180 in soil aging for 5 month) to 119% (PCB52 in soil aging for 1 month), indicating that not all PCBs was available for absorption after ingestion of soil samples. The bioaccessibility was assessed using both physiologically-based extraction test (PBET) and Tenax improved PBET (TI-PBET). Acceptable in vivo-in vitro correlation (r2 = 0.70 and slope = 1.30 ± 0.20) was observed for TI-PBET, not for PBET. Due to dominant role played by Tenax and bile, the TI-PBET was further simplified to Tenax and Tenax-bile extraction methods. However, poor in vivo-in vitro correlation (r2 = 0.14 and 0.05) was observed for the two simplified methods, which may be attributed to the combined effect between sorption sink and components in PBET. Therefore, in order to simply TI-PBET or standardize in vitro methods, it is highly necessary to explore the mechanism about the interaction between in vitro method components and sorption sink, or to screen key factors for bioaccessibility results in the future studies.

Bioaccessibility of PAHs in contaminated soils: Comparison of five in vitro methods with Tenax as a sorption sink.

For hydrophobic organic contaminants, physiologically based in vitro methods may need to include a sorption sink to simulate in vivo intestinal uptake. We compared PAH bioaccessibility in contaminated soils using five in vitro methods including physiologically based extraction test (PBET), in vitro digestion assay (IVD), method from Deutsches Institut für Normung (DIN), unified bioaccessibility method (UBM), and fed organic estimation human simulation test (FOREhST) in the absence and presence of Tenax as a sorption sink. The PAH bioaccessibility without Tenax were pretty low with values ranging from below detection limit to 13.4%, indicating the limited capacity of these in vitro models to accommodate PAHs. With addition of Tenax, bioaccessibility increased to 0.59-75.5% for all PAH congeners. Even with the dominant effect of sorption sink, bioaccessibility values significantly varied among all the five methods with DIN result being the highest at 7.0-34.8%. Based on multiple linear regression, Tenax, incubation time, and bile contents are identified to be the most important factors in controlling bioaccessibility. The understanding of these key factors for bioaccessibility is highly necessary to standardize in vitro methods, which helps to refine the assessment of health risk through exposure to ingested contaminants.

Precision combination therapy for triple negative breast cancer via biomimetic polydopamine polymer core-shell nanostructures.

Photothermal-based combination therapy using functional nanomaterials shows great promise in eradication of aggressive tumors and improvement of drug sensitivity. The therapeutic efficacy and adverse effects of drug combinations depend on the precise control of timely tumor-localized drug release. Here a polymer-dopamine nanocomposite is designed for combination therapy, thermo-responsive drug release and prevention of uncontrolled drug leakage. The thermo-sensitive co-polymer poly (2-(2-methoxyethoxy) ethyl methacrylate-co-oligo (ethylene glycol) methacrylate)-co-2-(dimethylamino) ethyl methacrylate-b-poly (D, l-lactide-co-glycolide) is constructed into core-shell structured nanoparticles for co-encapsulation of two cytotoxic drugs and absorption of small interfering RNAs against survivin. The drug-loaded nanoparticles are surface-coated with polydopamine which confers the nanoformulation with photothermal activity and protects drugs from burst release. Under tumor-localized laser irradiation, polydopamine generates sufficient heat, resulting in nanoparticle collapse and instant drug release within the tumor. The combination strategy of photothermal, chemo-, and gene therapy leads to triple-negative breast cancer regression, with a decrease in the chemotherapeutic drug dosage to about 1/20 of conventional dose. This study establishes a powerful nanoplatform for precisely controlled combination therapy, with dramatic improvement of therapeutic efficacy and negligible side effects.

Smart micelle@polydopamine core-shell nanoparticles for highly effective chemo-photothermal combination therapy.

In this investigation, we have designed and synthesized a novel core-shell polymer nanoparticle system for highly effective chemo-photothermal combination therapy. A nanoscale DSPE-PEG micelle encapsulating doxorubicin (Dox-M) was designed as a core, and then modified by a polydopamine (PDA) shell for photothermal therapy and bortezomib (Btz) administration (Dox-M@PDA-Btz). The facile conjugation of Btz to the catechol-containing PDA shell can form a reversible pH-sensitive boronic acid-catechol conjugate to create a stimuli-responsive drug carrier system. As expected, the micelle@PDA core-shell nanoparticles exhibited satisfactory photothermal efficiency, which has potential for thermal ablation of malignant tissues. In addition, on account of the PDA modification, both Dox and Btz release processes were pH-dependent and NIR-dependent. Both in vitro and in vivo studies illustrated that the Dox-M@PDA-Btz nanoparticles coupled with laser irradiation could enhance the cytotoxicity, and thus combinational therapy efficacy was achieved when integrating Dox, Btz, and PDA into a single nanoplatform. Altogether, our current study indicated that the micelle@polydopamine core-shell nanoparticles could be applied for NIR/pH-responsive sustained-release and synergized chemo-photothermal therapy for breast cancer.