RESUMO
The COVID-19 pandemic has spread to every corner of the world and seriously affected our health and daily activities in the past three years; thereby, it is still urgent to develop various simple, quick, and accurate methods for early detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nanozymes, a kind of nanomaterial with intrinsic enzyme-mimicking activity, have emerged as a suitable alternative for both therapy and diagnosis of SARS-CoV-2. Here, ultrasensitive and ultrafast MIL-101(CuFe)-CD147 biosensors are established for the detection of SARS-CoV-2 by a simple colorimetric method. A MIL-101(CuFe) metal-organic framework has excellent peroxidase-like activity due to the synergistic effect of Fe and Cu atoms. In addition, the MIL-101(CuFe)-CD147 biosensor shows great potential to detect the various variants of SARS-CoV-2 due to the universal receptor of CD147. The enzyme-based biosensor for the detection of SARS-CoV-2 achieves a very low limit of detection (about 3 PFU/mL) within 30 min. Therefore, the present method provides a new generation of an alternative approach for highly sensitive and visual diagnosis of COVID-19.
Assuntos
Técnicas Biossensoriais , COVID-19 , Estruturas Metalorgânicas , Humanos , Técnicas Biossensoriais/métodos , COVID-19/diagnóstico , Peroxidases , SARS-CoV-2RESUMO
Psoriasis is an incurable inflammatory skin disease that is mediated by the immune system. Although kaempferol has been known for its anti-inflammatory, antioxidant, and anticancer properties, its therapeutic effectiveness is often limited due to its poor water solubility and low bioavailability. To address these challenges, we developed a promising kaempferol hydrogel (DK-pGEL) using Pluronic F127 and a deep eutectic solvent (DES) with varying concentrations of kaempferol. In this study, we first evaluated the rheological properties and viscosity of the DK-pGEL hydrogel. The G' of DK-pGEL (â¼14 kPa) hydrogels was significantly lower than the control group (â¼30 kPa) at 37 °C. The DK-pGEL hydrogel exhibited ideal fluidity and viscosity at 37 °C, as demonstrated by its shear-thinning behavior. Moreover, the DK-pGEL hydrogel showed controlled release characteristics with a drug release of 97.43 ± 5.37 µg/mL over 60 h. Furthermore, in vitro antioxidant experiments revealed that DK-pGEL exhibited significant radical scavenging ability against the DPPH-radical (96.27 ± 0.37%), ABTS-radical (98.11 ± 0.79%), hydroxyl-radical (66.36 ± 1.01%), and superoxide-radical (90.52 ± 0.79%) at a concentration of 250 µg/mL kaempferol. Additionally, DK-pGEL exhibited notable cellular antioxidant effects by inhibiting reactive oxygen species generation. Cell viability assays (CCK8) and live/dead cell assays were conducted to assess the cytotoxicity of DK-pGEL. The results showed that DK-pGEL could effectively inhibit HaCaT cell proliferation without causing significant cytotoxicity. To evaluate the therapeutic potential of DK-pGEL, an imiquimod (IMQ)-induced mouse model of psoriasis-like lesions was employed. Remarkably, the DK-pGEL hydrogel could significantly reduce the psoriasis area and severity index score, improve the histopathology induced by IMQ, and downregulate the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-17A) in the skin tissue. These findings demonstrate that the DES-assisted kaempferol hydrogel holds promise as a topical drug delivery system for psoriasis treatment.
Assuntos
Solventes Eutéticos Profundos , Psoríase , Animais , Camundongos , Hidrogéis , Antioxidantes/uso terapêutico , Quempferóis/farmacologia , Inflamação/tratamento farmacológico , Psoríase/tratamento farmacológico , Pele , Imiquimode , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
Metal-organic frameworks (MOFs) are widely used to mimic enzymes for catalyzing chemical reactions; however, low enzyme activity limit their large-scale application. In this work, gold nanorods/metal-organic frameworks (Au NRs/Fe-MOF) hybrids were successfully synthesized for photo-enhanced peroxidase-like catalysis and surface-enhanced Raman spectroscopy (SERS). The enzyme-like activity of Au NRs/Fe-MOF hybrids was significantly enhanced under localized surface plasmon resonance (LSPR), because the hot electrons produced on Au NRs surface were transferred into Fe-MOF, activating the Fenton reaction by Fe3+/Fe2+ conversion and preventing the recombination of hot electrons and holes. This photo-enhanced enzyme-like catalytic performance was investigated by X-ray photoelectron spectrometry (XPS), electrochemical analysis, activation energy measurement, and in situ Raman spectroscopy. Afterward, Methylene Blue (MB) was chosen to demonstrate the photo-enhanced peroxidase-like performance of Au NRs/Fe-MOFs. The Au NRs/Fe-MOF caused chemical and electromagnetic enhancement of Raman signals and exhibited a great potential for the detection of toxic chemicals and biological molecules. The detection limit of MB concentration is 9.3 × 10-12 M. In addition, the Au NRs/Fe-MOF hybrids also showed excellent stability and reproducibility for photo-enhanced peroxidase-like catalysis. These results show that nanohybrids have great potential in many fields, such as sensing, cancer therapy, and energy harvesting.
Assuntos
Estruturas Metalorgânicas , Nanotubos , Corantes/química , Ouro/química , Estruturas Metalorgânicas/química , Azul de Metileno/química , Peroxidase/metabolismo , Peroxidases , Reprodutibilidade dos TestesRESUMO
Liver cancer is currently among the most challenging cancers to diagnose and treat. It is of prime importance to minimize the side effects on healthy tissues and reduce drug resistance for precise diagnoses and effective treatment of liver cancer. Herein, we report a facile but high-yield approach to fabricate a multifunctional nanomaterial through the loading of chitosan and metformin on Mn-doped Fe3O4@MoS2 nanoflowers. Mn-doped Fe3O4 cores are used as simultaneous T1/T2 magnetic resonance imaging (MRI) agents for sensitive and accurate cancer diagnosis, while MoS2 nanosheets are used as effective near-infrared photothermal conversion agents for potential photothermal therapy. The surface-functionalized chitosan was able not only to improve the dispersibility of Mn-doped Fe3O4@MoS2 nanoflowers in biofluids and increase their biocompatibility, but also to significantly enhance the photothermal effect. Furthermore, metformin loading led to high suppression and eradication of hepatoma cells when photothermally sensitized, but exhibited negligible effects on normal liver cells. Due to its excellent combination of T1/T2 MRI properties with sensitive chemotherapeutic and photothermal effects, our study highlights the promise of developing multifunctional nanomaterials for accurate multimodal imaging-guided, and highly sensitive therapy of liver cancer.
Assuntos
Dissulfetos/química , Óxido Ferroso-Férrico/química , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Manganês/química , Molibdênio/química , Nanoestruturas/química , Linhagem Celular Tumoral , Quitosana/química , Quitosana/uso terapêutico , Dissulfetos/uso terapêutico , Óxido Ferroso-Férrico/uso terapêutico , Humanos , Hipertermia Induzida/métodos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Imageamento por Ressonância Magnética/métodos , Manganês/uso terapêutico , Metformina/administração & dosagem , Metformina/uso terapêutico , Molibdênio/uso terapêutico , Imagem Multimodal/métodos , Nanoestruturas/uso terapêutico , Fototerapia/métodosRESUMO
Expression of Concern for 'One-pot synthesis of acid-degradable polyphosphazene prodrugs for efficient tumor chemotherapy' by Na Zhou et al., J. Mater. Chem. B, 2020, 8, 10540-10548, https://doi.org/10.1039/D0TB01992E.
RESUMO
Expression of concern for 'Intelligent nanoflowers: a full tumor microenvironment-responsive multimodal cancer theranostic nanoplatform' by Xunan Jing et al., Nanoscale, 2019, 11, 15508-15518, https://doi.org/10.1039/C9NR04768A.
RESUMO
Burn wound healing continues to pose significant challenges due to excessive inflammation, the risk of infection, and impaired tissue regeneration. In this regard, an antibacterial, antioxidant, and anti-inflammatory nanocomposite (called HPA) that combines a nanosystem using hexachlorocyclotriphosphazene and the natural polyphenol of Phloretin with silver nanoparticles (AgNPs) is developed. HPA effectively disperses AgNPs to mitigate any toxicity caused by aggregation while also showing the pharmacological activities of Phloretin. During the initial stage of wound healing, HPA rapidly releases silver ions from its surface to suppress bacterial activity. Moreover, these nanoparticles are pH-sensitive and degrade efficiently in the acidic infection microenvironment, gradually releasing Phloretin. This sustained release of Phloretin helps scavenge overexpressed reactive oxygen species in the infected microenvironment area, thus reducing the upregulation of pro-inflammatory cytokines. The antibacterial activity, free radical clearance, and regulation of inflammatory factors of HPA through in vitro experiments are validated. Additionally, its effects using an infectious burn mouse model in vivo are evaluated. HPA is found to promote collagen deposition and epithelialization in the wound area. With its synergistic antibacterial, antioxidant, and anti-inflammatory activities, as well as favorable biocompatibilities, HPA shows great promise as a safe and effective multifunctional nanoplatform for burn injury wound dressings.
Assuntos
Anti-Infecciosos , Queimaduras , Nanopartículas Metálicas , Infecção dos Ferimentos , Camundongos , Animais , Prata/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Antibacterianos/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Queimaduras/tratamento farmacológico , FloretinaRESUMO
Nanozymes are considered as the promising antimicrobial agents due to the enzyme-like activity for chemo-dynamic therapy (CDT). However, it remains a challenge to develop novel nanozyme systems for achieving stimuli-responsive, and efficient nanozyme catalysis with multimodal synergistic enhancement. In this work, a near-infrared (NIR) plasmonic-enhanced nanozyme catalysis and photothermal performance for effective antimicrobial applications are proposed. A Ti3 C2 MXene/Fe-MOFs composite (MXM) with NIR plasmonic-enhanced CDT combined with photothermal properties is successfully developed by loading metal-organic framework (MOF) nanozymes onto Ti3 C2 MXene. The mechanism of NIR induced localized surface plasmon resonance (LSPR)-enhanced CDT and photothermal therapy (PTT) is well explained through activation energy (Ea ), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS), fluorescence analysis experiments, and finite element simulation. It reveals that MXene nanosheets exhibit NIR plasmon exciters and generate hot electrons that can transfer to the surface of Fe-MOFs, promoting the Fenton reaction and enhances CDT. While the photothermal heating of MXene produced by LSPR can also boost the CDT of Fe-MOFs under NIR irradiation. Both in vitro and in vivo experimental results demonstrate that LSPR-induced MXM system has outstanding antimicrobial properties, can promote angiogenesis and collagen deposition, leading to the accelerated wound healing.
Assuntos
Anti-Infecciosos , Estruturas Metalorgânicas , Neoplasias , Nitritos , Elementos de Transição , Humanos , Estruturas Metalorgânicas/química , Ressonância de Plasmônio de Superfície , Neoplasias/terapia , Linhagem Celular TumoralRESUMO
Transition metal oxides as potentialanodes of lithium-ion batteries (LIBs) possess high theoretical capacity but suffer from large volume expansion and poor conductivity. To overcome these drawbacks, we designed and fabricated polyphosphazene-coated yolk-shelled CoMoO4 nanospheres, in which polyphosphazene with abundant C/P/S/N species was readily converted into carbon shells and provided P/S/N dopants. This resulted in the formation of P/S/N co-doped carbon-coated yolk-shelled CoMoO4 nanospheres (PSN-C@CoMoO4). The PSN-C@CoMoO4 electrode exhibits superior cycle stability of 439.2 mA h g-1at 1000 mA g-1after 500 cycles and rate capability of 470.1 mA h g-1at 2000 mA g-1. The electrochemical and structural analyses reveal that PSN-C@CoMoO4 with yolk-shell structure, coated with carbon and doped with heteroatom not only greatly enhances the charge transfer rate and reaction kinetics, but also efficiently buffers the volume variation upon lithiation/delithiation cycling. Importantly, the use of polyphosphazene as coating/doping agent can be a general strategy for developing advanced electrode materials.
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An excessive inflammatory response induced by cytokine storms is the primary reason for the deterioration of patients with acute lung injury (ALI). Though natural polyphenols such as curcumin (CUR) have anti-inflammation activity for ALI treatment, they often have limited efficacy due to their poor solubility in water and oxidising tendency. This study investigates a highly cross-linked polyphosphazene nano-drug (PHCH) developed by copolymerisation of CUR and acid-sensitive units (4-hydroxy-benzoic acid (4-hydroxy-benzylidene)-hydrazide, D-HBD) with hexachlorotripolyphosphonitrile (HCCP) for improved treatment of ALI. PHCH can prolong the blood circulation time and targeted delivery into lung inflammation sites by enhancing CUR's water dispersion and anti-oxidant properties. PHCH also demonstrates the inflammation-responsive release of CUR in an inflammation environment due to the acid-responsive degradation of hydrazine bonds and triphosphonitrile rings in PHCH. Therefore, PHCH has a substantial anti-inflammation activity for ALI treatment by synergistically improving CUR's water-solubility, bioavailability and biocompatibility. As expected, PHCH attenuates the cytokine storm syndrome and alleviates inflammation in the infected cells and tissues by down-regulating several critical inflammatory cytokines (TNF-α, IL-1ß, and IL-8). PHCH also decreases the expression of p-p65 and C-Caspase-1, inhibiting NLRP3 inflammasomes and suppressing NF-κB signalling pathways. The administrated mice experiments confirmed that PHCH accumulation was enhanced in lung tissue and showed the efficient scavenging ability of reactive oxygen species (ROS), effectively blocking the cytokine storm and alleviating inflammatory damage in ALI. This smart polyphosphazene nano-drug with targeting delivery property and inflammation-responsive release of curcumin has excellent potential for the clinical treatment of various inflammatory diseases, including ALI.
Assuntos
Lesão Pulmonar Aguda , Curcumina , Nanopartículas , Camundongos , Animais , Curcumina/química , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/metabolismo , Lipopolissacarídeos/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Pulmão/metabolismo , NF-kappa B/metabolismo , Nanopartículas/uso terapêuticoRESUMO
The microenvironment of excessive inflammation and the activation of apoptotic signals are primary barriers to neurological recovery following spinal cord injury (SCI). Thus, long-lasting anti-inflammation has become an effective strategy to navigate SCI. Herein, a curcumin (CUR)-containing nanosystem (FCTHPC) with high drug loading efficiency was reported via assembling hydrophobic CUR into cross-linked polyphosphazene (PPZ), and simultaneous loading and coordinating with porous bimetallic polymers for greatly enhanced the water-solubility and biocompatibility of CUR. The nanosystem is noncytotoxic when directing its biological activities. By inhibiting the expression of pro-inflammatory factors (IL-1ß, TNF-α and IL-6) and apoptotic proteins (C-caspase-3 and Bax/Bcl-2), which may be accomplished by activating the Wnt/ß-catenin pathway, the versatile FCTHPC can significantly alleviate the damage to tissues and cells caused by inflammation and apoptosis in the early stage of SCI. In addition, the long-term in vivo studies had demonstrated that FCTHPC could effectively inhibit the formation of glial scars, and simultaneously promote nerve regeneration and myelination, leading to significant recovery of spinal cord function. This study emphasises the promise of the biocompatible CUR-based nanosystem and provides a fresh approach to effectively treat SCI.
Assuntos
Curcumina , Nanopartículas , Traumatismos da Medula Espinal , Ratos , Animais , Curcumina/farmacologia , Curcumina/metabolismo , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/metabolismo , Anti-Inflamatórios/metabolismo , Polímeros/farmacologia , Apoptose , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Regeneração Nervosa , Nanopartículas/uso terapêuticoRESUMO
The choice of hemostatic technique is a curial concern for surgery and as first-aid treatment in combat. To treat uncontrolled bleeding in complex wound environments, chitosan-based hemostatic sponges have attracted significant attention in recent years because of the excellent biocompatibility, degradability, hemostasis and antibacterial properties of chitosan and their unique sponge-like morphology for high fluid absorption rate and priority aggregation of blood cells/platelets to achieve rapid hemostasis. In this review, we provide a historical perspective on the use of chitosan hemostatic sponges as the new generation of hemostatic materials for uncontrolled bleeding emergencies in complex wounds. We summarize the modification of chitosan, review the current status of preparation protocols of chitosan sponges based on various composite systems, and highlight the recent achievements on the detailed breakdown of the existing chitosan sponges to present the relationship between their composition, physical properties, and hemostatic capacity. Finally, the future opportunities and challenges of chitosan hemostatic sponges are also proposed.
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Quitosana , Hemostáticos , Humanos , Hemostáticos/farmacologia , Hemostáticos/uso terapêutico , Quitosana/uso terapêutico , Hemostasia , Hemorragia/tratamento farmacológico , PlaquetasRESUMO
Retraction of 'A tumor-microenvironment fully responsive nano-platform for MRI-guided photodynamic and photothermal synergistic therapy' by Daquan Wang et al., J. Mater. Chem. B, 2020, 8, 8271-8281, https://doi.org/10.1039/D0TB01373K.
RESUMO
On-demand designed theranostics nanoagents show promising applications for next-generation precision-and-personalized oncotherapy. Researchers have since aimed to develop nanoplatforms that can efficiently deliver drugs and contrast medium to tumor and release active ingredients in response to tumor microenvironment (TME) conditions. Herein, we propose a modular strategy, and develop a series of nanoplatforms based on metal-coordinated-polyprodrugs for cancer theranostics. The polyprodrugs were synthesized through a click-reaction between amino acid and doxorubicin (DOX) with dipropiolate. The backbones of the polyprodrugs had intrinsic sensitivities to pH and/or GSH, and provided abundant -COOH, -NH2, or -S-S- to chelate with functional metal ions and further self-assembled to form different morphologies. Dicysteine, which contains disulfide bond (-S-S-), was chosen to copolymerize with DOX and triethylene glycol dipropiolate (TEP) to prepare the pH/GSH dual-responsive polyprodrug poly(dicysteine-co-TEP-co-DOX) (pDTD), then separately coordinated with Gd3+, Fe3+, and Mn2+ to construct nanoplatforms pDTD@M (M representing the metal ions). In vitro and in vivo investigations suggest the metal-coordinated-polyprodrug nanoplatforms have good magnetic resonance imaging (MRI) ability and efficient tumor-growth inhibition with high safety. The design strategy of nanoplatforms based on metal-coordinated-polyprodrugs provides a new idea for on-demand construction of promising theranostics agents. STATEMENT OF SIGNIFICANCE: Compared to small molecule antitumor drugs, polymeric drugs have high drug loading ratio and are easily enriched at the tumor site to achieve improved therapy efficacy. This work utilizes click reactions to link amino acids with anticancer drugs to produce polymeric drugs that are degraded in response to tumor microenvironment and released small molecule antitumor drugs mainly in tumor sites, and subtly utilizes the coordination of amino acid to chelate MRI functional metal ion to realize enhanced MRI imaging mediated tumor therapy. This strategy provides a new idea for the convenient construction of polymeric drugs for tumor theranostics.
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Antineoplásicos , Nanopartículas , Neoplasias , Aminoácidos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Humanos , Íons , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Polímeros/química , Medicina de Precisão , Microambiente TumoralRESUMO
The unsatisfactory efficacy of conventional theranostic agents in ablating tumor poses urgent demands on the development of high-performance integrated theranostic agents utilizing rising nanotechnology. To cope with the existing limitations, here we presented an intelligent nanoplatform based on yolk-shell Fe3O4@polydopamine prepared by mussel-inspired polydopamine chemistry and sacrificial template method as well as subsequent incorporation of Pt nanoparticles and chlorine 6 (Ce6) by in situ reduction and electrostatic adsorption for photodynamic therapy (PDT) and photothermal (PTT). The resultant nanoplatform could effectively deliver photosensitizer Ce6 to tumor sites, then promoting the decomposition of endogenous H2O2 to oxygen, finally achieving enhanced PDT therapy, which is demonstrated by in vitro and in vivo evaluations. Importantly, the generated oxygen bubbles could improve the echogenicity signal of yolk-shell microspheres and thereby provide enhanced ultrasonic (US) signal for imaging solid tumors. Overall, the synergistic combination of magnetic Fe3O4, green polydopamine, catalytic Pt nanoparticles, photosensitive Ce6 enabled the hybrid nanoplatform to have good biocompatibility, efficient tumor accumulation, excellent phototherapy efficiency, high T2-weighted magnetic resonance imaging (MRI) and fluorescence imaging ability (FL). Our study integrating the merits of PDT/PTT and US/MRI/FL into a single nanoplatform will open an avenue of therapeutic strategy toward biomedical applications.
Assuntos
Nanopartículas , Fotoquimioterapia , Linhagem Celular Tumoral , Peróxido de Hidrogênio , Imagem Multimodal , Nanopartículas/química , Oxigênio , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , FototerapiaRESUMO
Aggregation-induced emission (AIE) nanoparticles have been widely applied in photodynamic therapy (PDT) over the past few years. However, amorphous nanoaggregates usually occur in their preparation, resulting in loose packing with disordered molecular structures. This still allows free intramolecular motions, thus leading to limited brightness and PDT efficiency. Herein, we report deep-red AIE nanocrystals (NCs) of DTPA-BS-F by following the facile method of nanoprecipitation. It is observed that DTPA-BS-F NCs possess not only a high photoluminescence quantum yield value of 8% in the deep-red region (600-850 nm) but also an impressive reactive oxygen species (ROS) generation efficiency of up to 69%. Moreover, DTPA-BS-F NCs targeting dual-organelles of lysosomes and nucleus to generate ROS are also achieved, thus boosting the PDT effect in cancer therapy both in vitro and in vivo. This work provides high-performance AIE NCs to simultaneously target two organelles for efficient photodynamic therapy, indicating their promising application in all-in-one theranostic platforms.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Medicina de Precisão , Espécies Reativas de Oxigênio , Organelas , Nanopartículas/química , Ácido Pentético , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica/métodos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológicoRESUMO
Nicotinamide adenine dinucleotide (NADH) is central to metabolism and implicated in various diseases. Herein, nanohybrids of gold nanostars and metal-organic frameworks are devised and demonstrated as a dual-mode NADH sensor, for which colorimetric detection is enabled by its peroxidase-like nanozyme property and Raman detection is realized by its surface-enhanced Raman scattering property with the detection limit as low as 28 pM. More importantly, this probe enables real-time SERS monitoring in living cells, providing a unique tool to investigate dynamic cellular processes involving NADH. Our experiments reveal that metabolism dynamics is accelerated by glucose and is much higher in cancerous cells. The SERS results can also be verified by the colorimetric detection. This sensor provides a new potential to detect biomarkers and their dynamics in situ.
Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Técnicas Biossensoriais/métodos , Glucose , Ouro , NAD , PeroxidaseRESUMO
In past decades, to improve the chemotherapeutic efficiency and reduce the systemic toxicity of small molecule anti-cancer drugs, polymer-based drug delivery systems (DDSs) have attracted great attention for tumor treatment due to their remarkable biocompatibility and responsive degradation in tumor microenvironment (TME). Herein, we developed a kind of pH-responsive and degradable hyperbranched polymeric nanocarriers via yne-phenol click-reaction of resveratrol (RSV) with bifunctional n-butyl dipropiolate (BDP) for efficient doxorubicin (DOX) delivery. The natural product RSV with three phenol groups has excellent antioxidant activity and synergetic enhancement for some anticancer drugs such as DOX. RSV tends to attack the alkynyl groups on BDP by nucleophilic addition in the presence of base as catalyst to afford hyperbranched polyprodrug (denoted as RB). PEGylated RB (termed as RBP) were further synthesized to improve the water solubility and prolong blood circulation by the click reaction of propiolate-terminated RB with amino terminated poly(ethylene glycol) (PEG-NH2). Interestingly, the RBP have high DOX loading ratio (â¼58.6 %) at neutral pH, but the vinyl-ether bonds in RB could break down at low pH conditions such as acidic TME (extracellular pHâ¼6.8, endosomes and lysosomes pHâ¼5.0) that leading to the targeting release of DOX and RSV. Therefore, the developed RBP@DOX nanoparticles exhibited high kill efficiency to tumor cells and slight damage to normal cells due to the effective delivery and release of DOX and RSV in tumor sites and the synergistic enhancement effect of two drugs.