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1.
Angew Chem Int Ed Engl ; : e202413417, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39352449

RESUMO

The substantial promotion of hydrogen evolution reaction (HER) catalytic performance relies on the breakup of the Sabatier principle, which can be achieved by the alternation of the support and electronic metal support interaction (EMSI) is noticed. Due to the utilization of tungsten disulfides as support for platinum (Pt@WS2), surprisingly, Pt@WS2 demands only 31 mV overpotential to attain 10 mA cm-2 in acidic HER test, corresponding to a 2.5-fold higher mass activity than benchmarked Pt/C. The pH dependent electrochemical measurements associated with H2-TPD and in-situ Raman spectroscopy indicate a hydrogen spillover involved HER mechanism is confirmed. The WS2 support triggers a higher hydrogen binding strength for Pt leading to the increment in hydrogen concentration at Pt sites proved by upshifted d band center as well as lower Gibbs free energy of hydrogen, favourable for hydrogen spillover. Besides, the WS2 shows a comparably lower effect on Gibbs free energy for different Pt layers (-0.50 eV layer-1) than carbon black (-0.88 eV layer-1) contributing to a better Pt utilization. Also, the theoretical calculation suggests the hydrogen spillover occurs on the 3rd Pt layer in Pt@WS2; moreover, the energy barrier is lowered with increment in hydrogen coverage on Pt.

2.
Adv Mater ; : e2409400, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39267457

RESUMO

Osteochondral injury is a prevalent condition for which no specific treatment is currently available. This study presents a piezoelectric-conductive scaffold composed of a piezoelectric cartilage-decellularized extracellular matrix (dECM) and piezoelectric-conductive modified gelatin (Gel-PC). The piezoelectricity of the scaffold is achieved through the modification of diphenylalanine (FF) assembly on the pore surface, while the conductive properties of scaffold are achieved by the incorporating poly(3,4-ethylenedioxythiophene). In vitro experiments demonstrate that bone marrow mesenchymal stem cells (BMSCs) undergo biphasic division during differentiation. In vivo studies using a Parma pig model of osteochondral defects demonstrate that the piezoelectric-conductive scaffold exhibits superior reparative efficacy. Notably, the generation of electrical stimulation is linked to joint movement. During joint activity, mechanical forces compress the scaffold, leading to deformation and the subsequent generation of an electric potential difference. The positive charges accumulated on the upper layer of the scaffold attract BMSCs, promoting their migration to the upper layer and chondrogenic differentiation. Meanwhile, the negative charges in the lower layer induce the osteogenic differentiation of BMSCs. Overall, this piezoelectric-conducive scaffold provides a promising platform for the effective repair of osteochondral defects.

3.
Chem Commun (Camb) ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324214

RESUMO

High entropy alloy nanoparticles encapsulated into nitrogen-doped carbon nanotubes show superior bifunctionality for the ORR and OER, evidenced by a battery performance of 214 mW cm-2, sustained for 200 h.

4.
Chem Commun (Camb) ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39344481

RESUMO

The faradaic efficiency of Bi2WO6 is 62.0% at -0.3 V vs. RHE, an improvement of 1.4- and 1.8-times relative to Bi2O3 and WO3 for the nitrate reduction reaction. In addition, the catalysis occurring on Bi2WO6 follows the pathway: *NO3-*NO2-*NO-*NOH-*HNOH-*H2NOH-*NH3, as verified by operando Raman spectroscopy and theoretical calculations.

5.
Sci Adv ; 10(28): eadn0960, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996025

RESUMO

Celastrol (CEL), an active compound isolated from the root of Tripterygium wilfordii, exhibits broad anticancer activities. However, its poor stability, narrow therapeutic window and numerous adverse effects limit its applications in vivo. In this study, an adenosine triphosphate (ATP) activatable CEL-Fe(III) chelate was designed, synthesized, and then encapsulated with a reactive oxygen species (ROS)-responsive polymer to obtain CEL-Fe nanoparticles (CEL-Fe NPs). In normal tissues, CEL-Fe NPs maintain structural stability and exhibit reduced systemic toxicity, while at the tumor site, an ATP-ROS-rich tumor microenvironment, drug release is triggered by ROS, and antitumor potency is restored by competitive binding of ATP. This intelligent CEL delivery system improves the biosafety and bioavailability of CEL for cancer therapy. Such a CEL-metal chelate strategy not only mitigates the challenges associated with CEL but also opens avenues for the generation of CEL derivatives, thereby expanding the therapeutic potential of CEL in clinical settings.


Assuntos
Trifosfato de Adenosina , Triterpenos Pentacíclicos , Pró-Fármacos , Espécies Reativas de Oxigênio , Triterpenos Pentacíclicos/farmacologia , Triterpenos Pentacíclicos/química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Trifosfato de Adenosina/metabolismo , Humanos , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Linhagem Celular Tumoral , Triterpenos/química , Triterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Quelantes/química , Quelantes/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Microambiente Tumoral/efeitos dos fármacos , Liberação Controlada de Fármacos , Nanopartículas/química , Ensaios Antitumorais Modelo de Xenoenxerto , Compostos Férricos/química
6.
Nano Lett ; 24(30): 9202-9211, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39037031

RESUMO

The formation of a protein corona gives nanomedicines a distinct biological identity, profoundly influencing their fate in the body. Nonspecific nanoparticle-protein interactions are typically highly heterogeneous, which can lead to unique biological behaviors and in vivo fates for individual nanoparticles that remain underexplored. To address this, we have established an in situ approach that allows quantitative examination of nanoparticle-protein adsorption at the individual nanoparticle level. This method integrates dual fluorescence quantification techniques, wherein the nanoparticles are first individually analyzed via nanoflow cytometry to detect fluorescent signals from adsorbed proteins. The obtained fluorescence intensity is then translated into protein quantities through calibration with microplate reader quantification. Consequently, this approach enables analysis of interparticle heterogeneity of nano-protein interactions, as well as in situ monitoring of protein adsorption kinetics and nanoparticle aggregation status in blood serum, preconditioning for a comprehensive understanding of nano-bio interactions, and predicting in vivo fate of nanomedicines.


Assuntos
Proteínas Sanguíneas , Nanopartículas , Adsorção , Nanopartículas/química , Proteínas Sanguíneas/química , Proteínas Sanguíneas/análise , Humanos , Coroa de Proteína/química , Fluorescência , Cinética
7.
Adv Mater ; 36(35): e2404971, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38935977

RESUMO

Cuproptosis is a novel copper-dependent programmed cell death. The efficacy of cuproptosis is highly dependent on intracellular copper accumulation and counteracted by a high level of glutathione (GSH) in tumor cells. Here, this work develops a self-amplified cuproptosis nanoparticles (Cel-Cu NP) using celastrol (Cel), a natural product isolated from medical plant. In Cel-Cu NP, Cel serves as a versatile copper ionophore, exhibiting an ideal coordination capacity toward copper ions without compromising the cuproptosis induction. Notably, Cel can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, this self-amplified cuproptosis further activates immunogenic cell death (ICD) to elicit robust immune response. Combining with immune checkpoint blockade, Cel-Cu NP effectively eradicates metastatic tumors in a mouse lung metastasis model. This study provides an efficient nanomedicine by inducing self-amplified cuproptosis for robust immunotherapy.


Assuntos
Cobre , Glutationa , Imunoterapia , Nanopartículas Metálicas , Triterpenos Pentacíclicos , Cobre/química , Triterpenos Pentacíclicos/química , Animais , Glutationa/metabolismo , Camundongos , Nanopartículas Metálicas/química , Linhagem Celular Tumoral , Humanos , Triterpenos/química , Triterpenos/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário
8.
Commun Chem ; 7(1): 131, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38851819

RESUMO

Nanoparticle-based therapies are emerging as a pivotal frontier in biomedical research, showing their potential in combating infections and facilitating wound recovery. Herein, selenium-tellurium dopped copper oxide nanoparticles (SeTe-CuO NPs) with dual photodynamic and photothermal properties were synthesized, presenting an efficient strategy for combating bacterial infections. In vitro evaluations revealed robust antibacterial activity of SeTe-CuO NPs, achieving up to 99% eradication of bacteria and significant biofilm inhibition upon near-infrared (NIR) irradiation. Moreover, in vivo studies demonstrated accelerated wound closure upon treatment with NIR-activated SeTe-CuO NPs, demonstrating their efficacy in promoting wound healing. Furthermore, SeTe-CuO NPs exhibited rapid bacterial clearance within wounds, offering a promising solution for wound care. Overall, this versatile platform holds great promise for combating multidrug-resistant bacteria and advancing therapeutic interventions in wound management.

9.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38892301

RESUMO

Leymus chinensis (Trin.) Tzvel., also known as the "Alkali Grass", is a major forage grass in the eastern and northeastern steppe vegetation in the Songnen Prairie. It is of great practical significance for grassland management to understand the influence of animal saliva on L. chinensis during animal feeding. In this study, we used clipping and daubing animal saliva to simulate responses to grazing by L. chinensis, and analyzed the physiological and metabolomic changes in response to simulated animal feeding. Results showed that the effects of animal saliva on physiological and metabolic processes of the treated plants produced a recovery phenomenon. Moreover, the effects of animal saliva produced a large number of differential metabolites related to several known metabolic pathways, among which the flavonoid biosynthesis pathway has undergone significant and persistent changes. We posit that the potential metabolic mechanisms of L. chinensis in response to simulated animal feeding are closely related to flavonoid biosynthesis.


Assuntos
Metaboloma , Metabolômica , Poaceae , Animais , Poaceae/metabolismo , Metabolômica/métodos , Flavonoides/metabolismo , Ração Animal , Saliva/metabolismo , Redes e Vias Metabólicas , Herbivoria
10.
Front Public Health ; 12: 1399704, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737855

RESUMO

Background: Fruits are essential for health, yet their consumption in children is inadequate, with unclear influencing factors. Methods: A cross-sectional study was conducted among students in grades 3-12 in Beijing, China, from September 2020 to June 2021. Fruit consumption in children was surveyed using a self-administered food frequency questionnaire. Additionally, children's food and nutrition literacy and family food environments were assessed using the "Food and Nutrition Literacy Questionnaire for Chinese School-age Children" and the "Family Food Environment Questionnaire for Chinese School-age Children," respectively. Results: Out of 10,000 participating children, 62.5% consumed fruit daily, with a lower frequency among boys (59.3%) compared to girls (65.8%), and among senior students (48.6%) compared to junior (63.6%) and primary students (71.2%). Fruit consumption was positively associated with other healthy foods (vegetables, whole grains, etc.) and negatively with unhealthy foods (sugared soft drinks). Children with higher food and nutrition literacy consumed fruits daily more frequently (82.4% vs. 59.9%, ORs = 2.438, 95%CI: 2.072-2.868). A significant positive correlation was found between children's fruit consumption and a healthy family food environment (66.4% vs. 50.2%, OR = 1.507, 95%CI: 1.363-1.667). Conclusion: The results indicate that individual food and nutrition literacy and family food environment are key positive predictors of children's fruit consumption. Future interventions should focus on educating children and encouraging parents to foster supportive family environments.


Assuntos
Frutas , Humanos , Feminino , Masculino , Estudos Transversais , Criança , Inquéritos e Questionários , Comportamento Alimentar , Pequim , Adolescente , China , Estudantes/estatística & dados numéricos , Letramento em Saúde/estatística & dados numéricos , Família
11.
Adv Sci (Weinh) ; 11(26): e2402208, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38704692

RESUMO

Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG-Mngel) formed by crosslinking sodium alginate (SA) with manganese-doped bioactive glass (BG-Mn) is developed as a versatile platform for anti-tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn2+ within bioactive glass (BG) can activate the cGAS-STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune-suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn2+ promotes cell migration in vitro. When combining BG-Mngel with anti-PD-1 antibody (α-PD-1) for the treatment of malignant melanoma, it shows enhanced anti-tumor immune response and long-term immune memory response. Remarkably, BG-Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full-thickness wounds. Overall, BG-MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.


Assuntos
Hidrogéis , Melanoma , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Camundongos , Melanoma/terapia , Melanoma/patologia , Modelos Animais de Doenças , Hipertermia Induzida/métodos , Humanos , Metástase Neoplásica , Linhagem Celular Tumoral , Raios Infravermelhos/uso terapêutico
12.
Adv Mater ; 36(30): e2402452, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38691849

RESUMO

The in vivo fate of chemotherapeutic drugs plays a vital role in understanding the therapeutic outcome, side effects, and the mechanism. However, the lack of imaging abilities of drugs, tedious labeling processes, and premature leakage of imaging agents result in loss of fidelity between the drugs and imaging signals. Herein, an amphiphilic polymer is created by copolymerization of a near-infrared-II (NIR-II) fluorophore tracer (T) and an anticancer Pt(IV) prodrug (D) of cisplatin in a hand-holding manner into one polymer chain for the first time. The obtained PolyplatinDT is capable of delivering the drugs and the fluorophores concomitantly at a precise D/T ratio, thereby resulting in tracking the platinum drugs and even readout of them in real-time via NIR-II imaging. PolyplatinDT can self-assemble into nanoparticles, referred to as NanoplatinDT. Furthermore, a caspase-3 cleavable peptide that serves as an apoptosis reporter is attached to NanoplatinDT, resulting in NanoplatinDTR that are capable of simultaneously tracking platinum drugs and evaluating the therapeutic efficacy. Overall, it is reported here the design of the first theranostic polymer with anticancer drugs, drug tracers, and drug efficacy reporters that can work in concert to provide insight into the drug fate and mechanism of action.


Assuntos
Antineoplásicos , Corantes Fluorescentes , Pró-Fármacos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Humanos , Corantes Fluorescentes/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Cisplatino/química , Cisplatino/farmacologia , Nanopartículas/química , Animais , Linhagem Celular Tumoral , Polímeros/química , Camundongos , Imagem Óptica , Apoptose/efeitos dos fármacos , Portadores de Fármacos/química
13.
J Pharm Anal ; 14(3): 389-400, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618248

RESUMO

Antibody-drug conjugates (ADCs) are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells, thereby attracting considerable attention in precise oncology therapy. Cetuximab (Cet) is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma (cSCC); however, its anti-tumor activity is limited to a single use. Cisplatin (CisPt) shows good curative effects; however, its adverse effects and non-tumor-targeting ability are major drawbacks. In this study, we designed and developed a new ADC based on a new cytotoxic platinum (IV) prodrug (C8Pt(IV)) and Cet. The so-called antibody-platinum (IV) prodrugs conjugates, named Cet-C8Pt(IV), showed excellent tumor targeting in cSCC. Specifically, it accurately delivered C8Pt(IV) into tumor cells to exert the combined anti-tumor effect of Cet and CisPt. Herein, metabolomic analysis showed that Cet-C8Pt(IV) promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells, thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum (IV) prodrugs conjugates.

14.
ACS Nano ; 18(17): 10979-11024, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38635910

RESUMO

Nanomaterials have attractive physicochemical properties. A variety of nanomaterials such as inorganic, lipid, polymers, and protein nanoparticles have been widely developed for nanomedicine via chemical conjugation or physical encapsulation of bioactive molecules. Superior to traditional drugs, nanomedicines offer high biocompatibility, good water solubility, long blood circulation times, and tumor-targeting properties. Capitalizing on this, several nanoformulations have already been clinically approved and many others are currently being studied in clinical trials. Despite their undoubtful success, the molecular mechanism of action of the vast majority of nanomedicines remains poorly understood. To tackle this limitation, herein, this review critically discusses the strategy of applying multiomics analysis to study the mechanism of action of nanomedicines, named nanomedomics, including advantages, applications, and future directions. A comprehensive understanding of the molecular mechanism could provide valuable insight and therefore foster the development and clinical translation of nanomedicines.


Assuntos
Nanomedicina , Humanos , Animais , Nanoestruturas/química , Genômica
15.
Molecules ; 29(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474662

RESUMO

Tussah silk is one of the most widely used wild silks. It is usually dyed with acid dyes, despite the shortcoming of poor wet fastness. Reactive dyeing is a good solution to this problem. In our work, sulfatoethylsulfone (SES), sulfatoethylsulfone/monochlorotriazine (SES/MCT), monochlorotriazine (MCT), and bis(monochlorotriazine) (Bis(MCT)) dyes were used to dye tussah silk. All of these dyes showed lower exhaustion and fixation on tussah silk than on mulberry silk under alkaline conditions. Among them, SES dyes were more applicable, with a fixation of 70-85% (at 4%owf dye) at 90 °C when using sodium bicarbonate as an alkali. SES dyes also showed a rapid fixation speed. The dyeing of tussah silk required lower sodium bicarbonate dosage, the use of more neutral electrolytes, and a higher dye quantity to achieve deep effects compared to mulberry silk. Dyed tussah silk displayed lower apparent color depth and brilliance than dyed mulberry silk. The neutral boiling dyeing of tussah silk with SES dyes exhibited higher exhaustion, higher fixation (82-92% at 4%owf dye), and a slower fixation speed compared with alkaline dyeing. Furthermore, in this dyeing method, SES dyes showed higher and more efficient fixation on tussah silk than on mulberry silk. All dyed tussah silk had excellent color fastness to soaping.


Assuntos
Morus , Seda , Corantes , Bicarbonato de Sódio
16.
Adv Mater ; 36(19): e2312583, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38302690

RESUMO

Hollow multishelled structures (HoMSs) are attracting great interest in lithium-ion batteries as the conversion anodes, owing to their superior buffering effect and mechanical stability. Given the synthetic challenges, especially elemental diffusion barrier in the multimetal combinations, this complex structure design has been realized in low- and medium-entropy compounds so far. It means that poor reaction reversibility and low intrinsic conductivity remain largely unresolved. Here, a hollow multishelled (LiFeZnNiCoMn)3O4 high entropy oxide (HEO) is developed through integrating molecule and microstructure engineering. As expected, the HoMS design exhibits significant targeting functionality, yielding satisfactory structure and cycling stability. Meanwhile, the abundant oxygen defects and optimized electronic structure of HEO accelerate the lithiation kinetics, while the retention of the parent lattice matrix enables reversible lithium storage, which is validated by rigorous in situ tests and theoretical simulations. Benefiting from these combined properties, such hollow multishelled HEO anode can deliver a specific capacity of 967 mAh g-1 (89% capacity retention) after 500 cycles at 0.5 A g-1. The synergistic lattice and volume stability showcased in this work holds great promise in guiding the material innovations for the next-generation energy storage devices.

17.
Biomater Sci ; 12(5): 1079-1114, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38240177

RESUMO

Hydrogels, formed from crosslinked hydrophilic macromolecules, provide a three-dimensional microenvironment that mimics the extracellular matrix. They served as scaffold materials in regenerative medicine with an ever-growing demand. However, hydrogels composed of only organic components may not fully meet the performance and functionalization requirements for various tissue defects. Composite hydrogels, containing inorganic components, have attracted tremendous attention due to their unique compositions and properties. Rigid inorganic particles, rods, fibers, etc., can form organic-inorganic composite hydrogels through physical interaction and chemical bonding with polymer chains, which can not only adjust strength and modulus, but also act as carriers of bioactive components, enhancing the properties and biological functions of the composite hydrogels. Notably, incorporating environmental or stimulus-responsive inorganic particles imparts smartness to hydrogels, hence providing a flexible diagnostic platform for in vitro cell culture and in vivo tissue regeneration. In this review, we discuss and compare a set of materials currently used for developing organic-inorganic composite hydrogels, including the modification strategies for organic and inorganic components and their unique contributions to regenerative medicine. Specific emphasis is placed on the interactions between the organic or inorganic components and the biological functions introduced by the inorganic components. The advantages of these composite hydrogels indicate their potential to offer adaptable and intelligent therapeutic solutions for diverse tissue repair demands within the realm of regenerative medicine.


Assuntos
Hidrogéis , Medicina Regenerativa , Medicina Regenerativa/métodos , Hidrogéis/química , Matriz Extracelular/química , Substâncias Macromoleculares , Polímeros/análise , Engenharia Tecidual/métodos
18.
Adv Sci (Weinh) ; 11(13): e2309388, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38269649

RESUMO

Cuproptosis, an emerging form of programmed cell death, has received tremendous attention in cancer therapy. However, the efficacy of cuproptosis remains limited by the poor delivery efficiency of copper ion carriers. Herein, copper complex nanoparticles (denoted as Cu(I) NP) are developed that can efficiently deliver copper complex into cancer cells to induce cuproptosis. Cu(I) NP demonstrate stimulus-responsive release of copper complexes, which results in mitochondrial dysfunction and promotes the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), leading to cuproptosis. Notably, Cu(I) NP not only induce cuproptosis, but also elicit robust immune responses to suppress tumor growth. Overall, this study provides a promising strategy for cuproptosis-based cancer therapy.


Assuntos
Nanopartículas , Neoplasias , Cobre , Imunoterapia , Apoptose , Neoplasias/terapia
19.
Small Methods ; 8(3): e2300812, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37906035

RESUMO

The development of nucleic acid-based drugs holds great promise for therapeutic applications, but their effective delivery into cells is hindered by poor cellular membrane permeability and inherent instability. To overcome these challenges, delivery vehicles are required to protect and deliver nucleic acids efficiently. Silica nanoparticles (SiNPs) have emerged as promising nanovectors and recently bioregulators for gene delivery due to their unique advantages. In this review, a summary of recent advancements in the design of SiNPs for nucleic acid delivery and their applications is provided, mainly according to the specific type of nucleic acids. First, the structural characteristics and working mechanisms of various types of nucleic acids are introduced and classified according to their functions. Subsequently, for each nucleic acid type, the use of SiNPs for enhancing delivery performance and their biomedical applications are summarized. The tailored design of SiNPs for selected type of nucleic acid delivery will be highlighted considering the characteristics of nucleic acids. Lastly, the limitations in current research and personal perspectives on future directions in this field are presented. It is expected this opportune review will provide insights into a burgeoning research area for the development of next-generation SiNP-based nucleic acid delivery systems.


Assuntos
Nanopartículas , Ácidos Nucleicos , Dióxido de Silício/química , Ácidos Nucleicos/genética , Ácidos Nucleicos/uso terapêutico , Nanopartículas/química
20.
Adv Mater ; 36(11): e2310456, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38092007

RESUMO

Pyroptosis, an emerging mechanism of programmed cell death, holds great potential to trigger a robust antitumor immune response. Platinum-based chemotherapeutic agents can induce pyroptosis via caspase-3 activation. However, these agents also enhance cyclooxygenase-2 (COX-2) expression in tumor tissues, leading to drug resistance and immune evasion in pancreatic cancer and significantly limiting the effectiveness of chemotherapy-induced pyroptosis. Here, an amphiphilic polymer (denoted as PHDT-Pt-In) containing both indomethacin (In, a COX-2 inhibitor) and platinum(IV) prodrug (Pt(IV)) is developed, which is responsive to glutathione (GSH). This polymer self-assemble into nanoparticles (denoted as Pt-In NP) that can disintegrate in cancer cells due to the GSH responsiveness, releasing In to inhibit the COX-2 expression, hence overcoming the chemoresistance and amplifying cisplatin-induced pyroptosis. In a pancreatic cancer mouse model, Pt-In NP significantly inhibit tumor growth and elicit both innate and adaptive immune responses. Moreover, when combined with anti-programmed death ligand (α-PD-L1) treatment, Pt-In NP demonstrate the ability to completely suppress metastatic tumors, transforming "cold tumors" into "hot tumors". Overall, the sustained release of Pt(IV) and In from Pt-In NP amplifies platinum-drug-induced pyroptosis to elicit long-term immune responses, hence presenting a generalizable strategy for pancreatic cancer.


Assuntos
Nanopartículas , Neoplasias Pancreáticas , Pró-Fármacos , Animais , Camundongos , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Platina , Ciclo-Oxigenase 2 , Piroptose , Cisplatino/farmacologia , Nanopartículas/uso terapêutico , Polímeros , Neoplasias Pancreáticas/tratamento farmacológico , Linhagem Celular Tumoral
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