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1.
Small ; 20(38): e2401387, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38773909

RESUMO

Bulk hexagonal boron nitride (h-BN) ceramics with structural integrity, high-temperature resistance and low expansion rate are expected for multifunctional applications in extreme conditions. However, due to its sluggish self-diffusion and intrinsic inertness, it remains a great challenge to overcome high-energy barrier for h-BN powder sintering. Herein, a cross-linking and pressureless-welding strategy is reported to produce bulk boron nitride nanosheets (BNNSs) ceramics with well-crystalized and dense B-N covalent-welding frameworks. The essence of this synthesis strategy lies in the construction of >B─O─H2C─H2C─H2N:→B< bond bridge connection structure among hydroxyl functionalized BNNSs (BNNSs-OH) using bifunctional monoethanolamine (MEA) as cross-linker through esterification and intermolecular-coordination reactions. The prepared BNNSs-interlaced ceramics have densities not less than 1.2 g cm-3, and exhibit exceptional mechanical robustness and resiliency, excellent thermomechanical stability, ultra-low linear thermal expansion coefficient of 0.06 ppm °C-1, and high thermal diffusion coefficient of 4.76 mm2 s-1 at 25 °C and 3.72 mm2 s-1 at 450 °C. This research not only reduces the free energy barrier from h-BN particles to bulk ceramics through facile multi-step physicochemical reaction, but also stimulates further exploration of multifunctional applications for bulk h-BN ceramics over a wide temperature range.

2.
Mol Pharm ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39351992

RESUMO

Intracellular copper ion homeostasis has become an attractive target for cancer therapy. Herein, we report a 2,2'-dipicolylamine (DPA) functionalized polyglutamate derivative (PDHB) which is capable of rapidly forming PDHB-copper complex (PDHB@Cu) due to the strong coordination ability of pendant DPA with Cu2+. High drug loading content of doxorubicin (DOX) (>30 wt %) is realized due to the strong affinity of Cu2+ to DOX, while that is about 10 wt % for PDHB without Cu2+. The obtained PDHB@Cu-DOX can respond to specific endogenous stimuli (pH and glutathione (GSH)), releasing Cu2+ and DOX. The released DOX directly damages the DNA of tumor cells to cause apoptosis, while Cu2+ depletes intracellular GSH and is reduced to Cu+ simultaneously, which reacts with local H2O2 to produce highly toxic ·OH via a Fenton-like reaction, thus realizing synergistic chemodynamics and chemotherapy. This report provides an interesting polymeric ionophore strategy to deliver enough copper ions into cancer cells, which can also easily extend to other metal ions by replacing the ionophore components, thus having a wide application in nanomedicine.

3.
Macromol Rapid Commun ; : e2400549, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39137300

RESUMO

Aqueous emulsion polymerization is a robust technique for preparing nanoparticles of block copolymers; however, it typically yields spherical nanoassemblies. The scale preparation of nanoassemblies with nonspherical high-order morphologies is a challenge, particularly 2D core-shell nanosheets. In this study, the polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are combined to demonstrate the preparation of 2D nanosheets and their aggregates via aqueous reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization. First, the crucial crystallizable component for CDSA, hydroxyethyl methacrylate polycaprolactone (HPCL) macromonomer is synthesized by ring opening polymerization (ROP). Subsequently, the RAFT emulsion polymerization of HPCL is conducted to generate crystallizable nanomicelles by a grafting-through approach. This PISA process simultaneously prepared spherical latices and bottlebrush block copolymers comprising poly(N',N'-dimethylacrylamide)-block-poly(hydroxyethyl methacrylate polycaprolactone) (PDMA-b-PHPCL). The latexes are now served as seeds for inducing the formation of 2D hexagonal nanosheets, bundle-shaped and flower-like aggregation via the CDSA of PHPCL segments and unreacted HPCL during cooling. Electron microscope analysis trace the morphology evolution of these 2D nanoparticles and reveal that an appropriate crystallized component of PHPCL blocks play a pivotal role in forming a hierarchical structure. This work demonstrates significant potential for large-scale production of 2D nanoassemblies through RAFT emulsion polymerization.

4.
Sensors (Basel) ; 24(15)2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39124086

RESUMO

The development of fluorescent molecular imprinting sensors for direct, rapid, and sensitive detection of small organic molecules in aqueous systems has always presented a significant challenge in the field of detection. In this study, we successfully prepared a hydrophilic colloidal molecular imprinted polymer (MIP) with 2,4-dichlorophenoxyacetic acid (2,4-D) using a one-pot approach that incorporated polyglycerol methacrylate (PGMMA-TTC), a hydrophilic macromolecular chain transfer agent, to mediate reversible addition-fragmentation chain transfer precipitation polymerization (RAFTPP). To simplify the polymerization process while achieving ratiometric fluorescence detection, red fluorescent CdTe quantum dots (QDs) and green fluorescent nitrobenzodiazole (NBD) were introduced as fluorophores (with NBD serving as an enhancer to the template and QDs being inert). This strategy effectively eliminated background noise and significantly improved detection accuracy. Uniform-sized MIP microspheres with high surface hydrophilicity and incorporated ratiometric fluorescent labels were successfully synthesized. In aqueous systems, the hydrophilic ratio fluorescent MIP exhibited a linear response range from 0 to 25 µM for the template molecule 2,4-D with a detection limit of 0.13 µM. These results demonstrate that the ratiometric fluorescent MIP possesses excellent recognition characteristics and selectivity towards 2,4-D, thus, making it suitable for selective detection of trace amounts of pesticide 2,4-D in aqueous systems.

5.
Nano Lett ; 23(22): 10608-10616, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37948661

RESUMO

The rarity of efficient tools with spatiotemporal resolution and biocompatibility capabilities remains a major challenge for further progress and application of signaling manipulation. Herein, biomimetic conjugated oligomeric nanoparticles (CM-CONs) were developed to precisely modulate blood glucose homeostasis via the two-pronged activation of calcium channels. Under near-infrared (NIR) laser irradiation, CM-CONs efficiently generate local heat and reactive oxygen species (ROS), thereby simultaneously activating thermosensitive transient receptor potential V1 (TRPV1) and ROS-sensitive transient receptor potential A1 (TRPA1) calcium channels in small intestinal endocrine cells. The activation of the channels mediates inward calcium flow and then promotes glucagon-like peptide (GLP-1) secretion. Both in vitro and in vivo studies indicate that CM-CONs effectively regulate glucose homeostasis in diabetic model mice upon NIR light irradiation. This work develops a two-pronged attack strategy for accurately controlling blood glucose homeostasis, holding great prospects in the treatment for diabetes.


Assuntos
Glicemia , Nanopartículas , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Canais de Cálcio , Homeostase , Cálcio/metabolismo
6.
Opt Lett ; 48(17): 4697-4700, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656589

RESUMO

Four phthalocyanine derivatives with different electron donor and acceptor substituents (B1, B2, B3, and B4) were synthesized by a solid-phase melting method. The influence of substituent type on the nonlinear optical properties of the materials was investigated in detail. In the case of similar conjugated structures, B3, which has amino electron-donor groups, presents high intramolecular charge transfer, a low energy gap (2.05 eV), and good nonlinear optical properties. Compared with B3, B4 has a larger π-conjugated structure and its energy gap is 0.04 eV smaller. Moreover, B4 has stronger reverse saturation absorption (7 × 10-12 m/W) and optical limiting performance. The four phthalocyanine derivatives exhibit third harmonic generation (THG) characteristics. Furthermore, the third harmonic strengths of B1, B2, B3, and B4 are 4 times, 9 times, 11 times, and 21 times that of SiO2, respectively. So, B4 has the best application potential in laser protection and frequency conversion.

7.
Chemistry ; 29(1): e202202787, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36196504

RESUMO

The development of new vinylene-linked covalent organic frameworks (COFs) with special ionic structure and high stability is challenging. Herein, we report a facile, general method for constructing ionic vinylene-linked thiopyrylium-based COFs from 2,4,6-trimethylpyrylium tetrafluoroborate and other common reagents by means of acid-catalyzed Aldol condensation. Besides, pyrylium-, and pyridinium-based COFs also can be prepared from the same monomer under slightly different reaction conditions. The COFs exhibited uniform nanofibrous morphologies with excellent crystallinities, special ionic structures, well-defined nanochannels, and high specific surface areas.

8.
Appl Opt ; 62(10): 2493-2500, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132797

RESUMO

The pyrene derivative (PD) was synthesized with pyrene-1-carboxaldehyde and p-aminoazobenzene by a Schiff base reaction. Then the obtained PD was dispersed in polyurethane (PU) prepolymer to prepare polyurethane/pyrene derivative PU/PD materials with good transmittance. The nonlinear optical (NLO) performances of the PD and PU/PD materials were studied by the Z-scan technique under picosecond and femtosecond laser pulses. The PD has reverse saturable absorption (RSA) properties under the excitation of 532 nm 15 ps pulses, 650 and 800 nm 180 fs pulses, and a low optical limiting (OL) threshold (0.01J/c m 2). The PU/PD has a larger RSA coefficient than that of the PD under 532 nm 15 ps pulses. With the enhanced RSA, the PU/PD materials exhibit excellent OL (OL) performance. Good NLO properties, high transparency, and easy processing performances make the PU/PD an excellent choice for use in OL and laser protection fields.

9.
Nanotechnology ; 33(22)2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35158345

RESUMO

The practical application of lithium-sulfur battery is seriously limited by the loss of active substances and the deterioration of cycle stability caused by the 'shuttle effect' of lithium polysulfides (LiPSs). In this work, graphene oxide (GO) coated covalent organic framework (COF) compound materials were synthesized as sulfur host material in spray-drying process. The polar groups on COF can efficiently adsorb LiPSs through lithiophilic interaction, which can reduce the 'shuttle effect' caused by soluble LiPSs. Besides, GO in the outer layer can wrap discrete sulfur to reduce the loss of active substances, which further improves the cycle stability of the cathode. The COF@GO/S cathode exhibits a high initial specific capacity of 848.4 mAh g-1and retains a capacity of 601.1 mAh g-1after 500 cycles at 1 C counting with a low capacity fading of 0.058% per cycle.

10.
Macromol Rapid Commun ; 43(11): e2200135, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35365902

RESUMO

The development of biomimetic extracellular matrix (ECM) with fibrous structure and complex nonlinear mechanics has been attracting intensive attention over the past decades both in material science and tissue engineering. Polyisocyanopeptide (PIC) hydrogels are a class of fully synthetic materials that can mimic biogels, such as fibrin and collagen, in nearly all aspects, particularly the micron-sized gel network and the strong strain-stiffening behavior in the biological regime. Here, a biomimetic PIC/hydroxyapatite (HA) hybrid composite through an enzymatic biomineralization strategy is constructed. HA biominerals grew on PIC bundles in situ catalyzed by the embedded alkaline phosphatase (ALP), which further crosslinked the gel networks and reinforced the mechanical property of PIC hydrogels. Significantly, PIC/HA composites exhibited ultra-responsive nonlinear mechanics with higher sensitivity to mechanical stress compared with those without biomineralization. As a consequence, the presence of HA can provide cell adhesion sites for PIC gels and induce osteogenic differentiation of pre-osteoblasts by virtue of the changes in mechanical properties. With these outstanding properties, therefore, PIC/HA composites present promising prospects in bone tissue engineering as biomimetic ECM.


Assuntos
Durapatita , Osteogênese , Durapatita/química , Hidrogéis/química , Osteoblastos , Engenharia Tecidual , Alicerces Teciduais/química
11.
Nanotechnology ; 32(8): 085402, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33091887

RESUMO

In order to improve the electrochemical capacity of lithium-sulfur batteries (LiSBs), it is necessary to introduce the porous organic frameworks with well-defined hetero atom species in cathode. In this work, porous nanomaterials with ultra-high nitrogen containing and adjustable porosity named Schiff-based networks (SNWs) were selected as potential candidate for sulfur host in LiSBs. Two SNW samples have been constructed by reacting melamine with phenyl or biphenyl dialdehydes through microwave-assisted method, respectively. The high BET surface area provided sufficient room to impregnate sulfur and mitigated volume changes during the cycling performance. Besides, the high density and homogeneous distribution of pyridinic-N and aminic-N in SNW nanoparticles can cooperatively form lithium polysulfides (LiPSs) chemisorption via enhanced Li+-N interactions to effectively suppressed the 'shuttle effect'. Attributed to its structural superiorities, SNW/S cathode demonstrates excellent electrochemical performance in LiSBs. In particular, SNW-2/S cathode delivers an excellent cyclability with a specific capacity of 620 mAh · g-1 after 500 cycles at 0.5 C, counting with a low capacity fading of 0.0508% per cycle. This work highlights the importance of rational design for effective LiPSs chemisorption and pioneers a facile strategy for developing suitable sulfur host materials towards high-performance LiSBs.

12.
J Nanosci Nanotechnol ; 18(5): 3291-3298, 2018 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442830

RESUMO

A new thermally conductive and electrically insulative polyimide were prepared by filling different amounts of hexagonal boron nitride (h-BN) particles, and the thermal conductivity of Polyimide (PI) composites were improved with the increasing h-BN content. Based on this, two methods were applied to improve thermal conductivity furtherly at limited filler loading in this paper. One is modifying the h-BN to improve interface interaction, another is fabricating a nano-micro hybrid filler with 2-D h-BN and 0-D nano-scale nanodiamond (ND) to build more effective conductive network. Both surface modification and hybrid system have a positive effect on thermal conductivity. The composites introducing 40 wt% hybrid filler (the weight ratio of ND/modified BN was 1/10) showed the highest thermal conductivity, being up to 0.98 W/(m K) (5.2 times that of PI). In addition, the composites exhibits excellent electrical insulation, thermal stability properties etc.

13.
J Nanosci Nanotechnol ; 17(1): 306-12, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-29620827

RESUMO

In this work, a simple and effective method for the covalent functionalization of nanodiamond (ND) with four epoxies has been developed. After homogenization by mixed acids and thionyl chlorides, the surface of ND was modified with triethylenetetramine (TETA) to possess amine groups, which were used as active points to react with epoxy by ring opening reaction. Four different epoxies used are bifunctional diglycidyl ether of bisphenol-A (DGEBA), trifunctional triglycidyl p-amino phenol (TGAP), tetrafunctional tetraglycidyldiamino diphenylmethane (TGDDM) and bisphenol-A novolac epoxy resin (BAEPN). FT-IR spectra revealed that the epoxy was covalently attached to the ND (ND-g-epoxy). In addition, functionalized ND particles were characterized with WAXD and UV-Vis spectra to confirm the result. The weight gains as a result of the epoxy-functionalized ND were determined by TGA analysis. The ND-g-epoxy particles were better dispersed in common organic solvents and the average diameters were characterized. The better dispersion and of the modified ND were identified from the SEM images.

14.
J Nanosci Nanotechnol ; 15(5): 3780-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26505005

RESUMO

Polyimide/multiwall carbon nanotube (PI/MWCNT) nanocomposite films with homogeneous MWCNTs dispersion were prepared via a solid state shearing pulverization (S3P) approach. Polyimide precursor, viz., poly(amic acid) (PAA), was synthesized from 4,4'-oxydianiline (ODA) and pyromellitic dianhydride (PMDA). Then, 3,3',4,4'-benzophenonetetracarboxylic dianhydride (BTDA) was mixed with the PAA powder and acid functionalized MWCNTs (acid-MWCNTs) by solid state shearing pulverization (S3P) approach. Finally, PI/MWCNT nanocomposite films were prepared by thermal imidization at elevated temperatures. Using such an approach not only the MWCNTs are well-dispersed but also the mechanical and thermal properties of PI are improved. The tensile strength of PI was enhanced by 74% and the elongation at break decreased to 10.35% with 5.0 wt% acid- MWCNT loading. And the glass transition temperature of PI was increased to 341 degrees C from 303 degrees C because of the strong interfacial bonding between PI and acid-MWCNTs. The solid state shearing pulverization (S3P) approach developed in this study provides a novel method to prepare various polymer composites with desired particle dispersion.


Assuntos
Nanocompostos/química , Nanotubos de Carbono/química , Polímeros/química , Nanotecnologia , Resistência à Tração
15.
RSC Adv ; 14(38): 27948-27956, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39224632

RESUMO

Exfoliated graphite platelets (EGPs) have attracted extensive attention owing to their exceptional combinations of thermal conductivity and mechanical properties. Mechanical exfoliation is a facile and high-throughput approach to produce single-layer or few-layer graphite platelets. Herein, octadecylamine (ODA)-grafted EGP (ODA@EGP) and subsequent polyethylene/ODA@EGP (PE/ODA@EGP) composites with different contents of ODA@EGPs were successfully prepared via ball-milling and melt-mixing methods, respectively. The thermal conductivity, crystallinity, and mechanical properties of the composites were investigated using tensile tests, the hot-wire method, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, and thermogravimetric analysis (TGA). The results demonstrated that the thermal conductivity, mechanical properties, and thermal stability of the composites can be improved by regulating the additive contents of ODA@EGPs. When the content of ODA@EGPs was 10 wt%, the thermal conductivity of the composite reached up to 1.276 W (m-1 K-1), which is 216% higher than that of bare PE, while the tensile strength of the composite was 38.4% higher than that of PE. Additionally, thermal decomposition temperature increased by 16.2 °C. Therefore, the PE/ODA@EGP nanocomposites have great application potential in thermal management.

16.
Acta Biomater ; 183: 278-291, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38838905

RESUMO

Anti-angiogenesis has emerged a promising strategy against colorectal cancer (CRC). However, the efficacy of anti-angiogenic therapy is greatly compromised by the up-regulated autophagy levels resulting from the evolutionary resistance mechanism and the presence of Fusobacterium nucleatum (F. nucleatum) in CRC. Herein, we report a cationic polymer capable of blocking autophagic flux to deliver plasmid DNA (pDNA) encoding soluble FMS-like tyrosine kinase-1 (sFlt-1) for enhanced anti-angiogenic therapy against F. nucleatum-associated CRC. The autophagy-inhibiting cationic polymer, referred to as PNHCQ, is synthesized by conjugating hydroxychloroquine (HCQ) into 3,3'-diaminodipropylamine-pendant poly(ß-benzyl-L-aspartate) (PAsp(Nors)), which can be assembled and electrostatically interacted with sFlt-1 plasmid to form PNHCQ/sFlt-1 polyplexes. Hydrophobic HCQ modification not only boosts transfection efficiency but confers autophagy inhibition activity to the polymer. Hyaluronic acid (HA) coating is further introduced to afford PNHCQ/sFlt-1@HA for improved tumor targeting without compromising on transfection. Consequently, PNHCQ/sFlt-1@HA demonstrates significant anti-tumor efficacy in F. nucleatum-colocalized HT29 mouse xenograft model by simultaneously exerting anti-angiogenic effects through sFlt-1 expression and down-regulating autophagy levels exacerbated by F. nucleatum challenge. The combination of anti-angiogenic gene delivery and overall autophagy blockade effectively sensitizes CRC tumors to anti-angiogenesis, providing an innovative approach for enhanced anti-angiogenic therapy against F. nucleatum-resident CRC. STATEMENT OF SIGNIFICANCE: Up-regulated autophagy level within tumors is considered responsible for the impaired efficacy of clinic antiangiogenic therapy against CRC colonized with pathogenic F. nucleatum. To tackle this problem, an autophagy-inhibiting cationic polymer is developed to enable efficient intracellular delivery of plasmid DNA encoding soluble FMS-like tyrosine kinase-1 (sFlt-1) and enhance anti-angiogenic therapy against F. nucleatum-associated CRC. HA coating that can be degraded by tumor-enriching hyaluronidase is further introduced for improved tumor targeting without compromising transfection efficiency. The well-orchestrated polyplexes achieve considerable tumor accumulation, efficient in vivo transfection, and effectively reinforce the sensitivity of CRC to the sFlt-1-derived anti-angiogenic effects by significantly blocking overall autophagy flux exacerbated by F. nucleatum challenge, thus harvesting robust antitumor outcomes against F. nucleatum-resident CRC.


Assuntos
Autofagia , Neoplasias Colorretais , Fusobacterium nucleatum , Fusobacterium nucleatum/efeitos dos fármacos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Animais , Autofagia/efeitos dos fármacos , Humanos , Técnicas de Transferência de Genes , Camundongos Nus , Camundongos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Terapia Genética/métodos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/patologia , Plasmídeos , Inibidores da Angiogênese/farmacologia , Hidroxicloroquina/farmacologia , Infecções por Fusobacterium/tratamento farmacológico , Infecções por Fusobacterium/complicações
17.
J Mater Chem B ; 12(16): 3947-3958, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38586917

RESUMO

Colorectal cancer (CRC) occurs in the colorectum and ranks second in the global incidence of all cancers, accounting for one of the highest mortalities. Although the combination chemotherapy regimen of 5-fluorouracil (5-FU) and platinum(IV) oxaliplatin prodrug (OxPt) is an effective strategy for CRC treatment in clinical practice, chemotherapy resistance caused by tumor-resided Fusobacterium nucleatum (Fn) could result in treatment failure. To enhance the efficacy and improve the biocompatibility of combination chemotherapy, we developed an antibacterial-based nanodrug delivery system for Fn-associated CRC treatment. A tumor microenvironment-activated nanomedicine 5-FU-LA@PPL was constructed by the self-assembly of chemotherapeutic drug derivatives 5-FU-LA and polymeric drug carrier PPL. PPL is prepared by conjugating lauric acid (LA) and OxPt to hyperbranched polyglycidyl ether. In principle, LA is used to selectively combat Fn, inhibit autophagy in CRC cells, restore chemosensitivity of 5-FU as well as OxPt, and consequently enhance the combination chemotherapy effects for Fn-associated drug-resistant colorectal tumor. Both in vitro and in vivo studies exhibited that the tailored nanomedicine possessed efficient antibacterial and anti-tumor activities with improved biocompatibility and reduced non-specific toxicity. Hence, this novel anti-tumor strategy has great potential in the combination chemotherapy of CRC, which suggests a clinically relevant valuable option for bacteria-associated drug-resistant cancers.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Fluoruracila , Ácidos Láuricos , Fluoruracila/farmacologia , Fluoruracila/química , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Humanos , Ácidos Láuricos/química , Ácidos Láuricos/farmacologia , Animais , Camundongos , Antineoplásicos/química , Antineoplásicos/farmacologia , Fusobacterium nucleatum/efeitos dos fármacos , Oxaliplatina/farmacologia , Oxaliplatina/química , Sistemas de Liberação de Medicamentos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Portadores de Fármacos/química
18.
ACS Appl Mater Interfaces ; 16(38): 50459-50473, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39258403

RESUMO

Insufficient drug accumulation in tumors severely limits the antitumor efficiency of hyaluronic acid (HA) nanomedicine in solid tumors due to superficial penetration depth, low cell uptake, and nonspecific drug release. Hence, we constructed a dual NO prodrug (alkynyl-JSK) and doxorubicin prodrug (cis-DOX)-conjugated HA nanoparticle (HA-DOX-JSK NPs), which achieved cascade-boosted drug delivery efficiency based on a relay strategy of NO-mediated deep tumor penetration─HA target CD44 tumor cell uptake─tumor microenvironment (TME)-responsive drug release. The nanoparticle demonstrated sustained and locoregionally GSH/GST-triggered NO release and GSH/pH-responsive DOX release in the tumor. The released NO first mediated collagen degradation, causing deep tumor penetration of nanoparticles in the dense extracellular matrix. Immediately, HA was relayed to enhance CD44-targeted tumor cell uptake, and then, the nanoparticles were finally triggered by specific TME to release DOX and NO in the deep tumor. Relying on the relayed delivery strategy, a significant improvement of DOX accumulation in tumors was realized. Moreover, NO depleted GSH-induced intracellular reactive oxygen species, enhancing DOX chemotherapy. Based on this strategy, the tumor inhibition rate in breast cancer was up to 87.8% in vivo. The relay drug-delivery HA system would greatly cascade-boost drug accumulation in deep tumors for efficient solid tumor therapy.


Assuntos
Doxorrubicina , Ácido Hialurônico , Nanopartículas , Estresse Oxidativo , Pró-Fármacos , Ácido Hialurônico/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Humanos , Animais , Nanopartículas/química , Camundongos , Feminino , Liberação Controlada de Fármacos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Linhagem Celular Tumoral , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Hialuronatos/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Antineoplásicos/química , Antineoplásicos/farmacologia , Camundongos Nus , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia
19.
Adv Healthc Mater ; : e2402297, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39175376

RESUMO

Bacterial infection-induced excessive inflammation is a major obstacle in diabetic wound healing. Nitric oxide (NO) exhibits significant antibacterial activity but is extremely deficient in diabetes. Hence, a near-infrared (NIR)-triggered NO release system is constructed through codelivery of polyarginine (PArg) and gold nanorods (Au) in an NIR-activatable methylene blue (MB) polypeptide-assembled nanovesicle (Au/PEL-PBA-MB/PArg). Upon NIR irradiation, the quenched MB in the nanovesicles is photoactivated to generate more reactive oxygen species (ROS) to oxidize PArg and release NO in an on-demand controlled manner. With the specific bacterial capture of phenylboronic acid (PBA), NO elevated membrane permeability and boosted bacterial vulnerability in the photothermal therapy (PTT) of the Au nanorods, which is displayed by superior mild PTT antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) at temperatures < 49.7 °C in vitro. Moreover, in vivo, the antibacterial nanovesicles greatly suppressed the burst of MRSA-induced excessive inflammation, NO relayed immunomodulated macrophage polarization from M1 to M2, and the excessive inflammatory phase is successfully transferred to the repair phase. In cooperation with angiogenesis by NO, tissue regeneration is accelerated in MRSA-infected diabetic wounds. Therefore, nanoplatform has considerable potential for accelerating the healing of infected diabetic wounds.

20.
Polymers (Basel) ; 15(14)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37514392

RESUMO

It is crucial to develop sensitive and accurate sensing strategies to detect H2O2 and glucose in biological systems. Herein, biocompatible iron-coordinated L-lysine-based hydrogen peroxide (H2O2)-mimetic enzymes (Lys-Fe-NPs) were prepared by precipitation polymerization in aqueous solution. The coordinated Fe2+ ion acted as centers of peroxidase-like enzymes of Lys-Fe-NPs, and the catalytic activity was evaluated via the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2. Therefore, a sensitive colorimetric detection sensor for H2O2 was constructed with a linear range of 1 to 200 µM and a detection limit of 0.51 µM. The same method could also be applied to highly sensitive and selective detection of glucose, with a linear range of 0.5 to 150 µM and a detection limit of 0.32 µM. In addition, an agarose-based hydrogel biosensor colorimetric was successfully implemented for visual assessment and quantitative detection of glucose. The design provided a novel platform for constructing stable and nonprotein enzyme mimics with lysine and showed great potential applications in biorelevant assays.

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