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1.
Artigo em Inglês | MEDLINE | ID: mdl-38634578

RESUMO

Excessive blood loss and infections are the prominent risks accounting for mortality and disability associated with acute wounds. Consequently, wound dressings should encompass adequate adhesive, hemostatic, and bactericidal attributes, yet their development remains challenging. This investigation presented the benefits of incorporating a perfluorocarbon nanoemulsion (PPP NE) into a silk-fibroin (SF)-based hydrogel. By stimulating the ß-sheet conformation of the SF chains, PPP NEs drastically shortened the gelation time while augmenting the elasticity, mechanical stability, and viscosity of the hydrogel. Furthermore, the integration of PPP NEs improved hemostatic competence by boosting the affinity between cells and biomacromolecules. It also endowed the hydrogel with ultrasound-controlled bactericidal ability through the inducement of inner cavitation by perfluorocarbon and reactive oxygen species (ROS) generated by the sonosensitizer protoporphyrin. Ultimately, we employed a laparotomy bleeding model and a Staphylococcus aureus-infected trauma wound to demonstrate the first-aid efficacy. Thus, our research suggested an emulsion-incorporating strategy for managing emergency wounds.

2.
ACS Appl Mater Interfaces ; 16(3): 3126-3138, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38191301

RESUMO

Developing strategies for the treatment of bacterial biofilms is challenging due to their complex and resilient structure, low permeability to therapeutics, and ability to protect resident pathogens. Herein, we demonstrate that a polylysine-stabilized perfluorocarbon nanoemulsion is favored for penetrating biofilms and sensitizing the cavitation effect of low-intensity ultrasound, resulting in the dispersal of extracellular polymeric substances and killing of the protected cells. Through experiments, we observed a complete penetration of the nanoemulsion in a 40 µm Pseudomonas aeruginosa biofilm and demonstrated that it was induced by the fluidic perfluorocarbon, possibly attributing to its low surface tension. Furthermore, we presented an almost complete antibiofilm effect with a low-intensity ultrasound (1 MHz, 0.75 W/cm2, 5 min) in diverse cases, including cultured biofilms, colonized urinary catheters, and chronic wounds. During the treatment process, the perfluorocarbon phase enhanced the number and imploding energy of ultrasound cavities, thoroughly divided the biofilm structure, prevented biofilm self-healing, and sterilized the resident pathogens. Thus, the penetration and sensitization of the nanoemulsion might serve as a facile and potent strategy for eradicating biofilms in various applications.


Assuntos
Antibacterianos , Infecções por Pseudomonas , Humanos , Antibacterianos/farmacologia , Biofilmes , Luz , Pseudomonas aeruginosa
3.
J Hazard Mater ; 465: 133075, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38016318

RESUMO

The environmental problem caused by industrial emissions of NOx has been studied in the past dacades. In this study, red mud coupling with phosphorus sludge were used to enhance the solution to absorb NOx from the flue gas. Firstly, red mud reacted with the binder silicic acid in the phosphorus sludge, destroying the emulsion structure of the phosphorus sludge. Then, the P4 in the phosphorus sludge is completely released, and the P4 reacted with O2 in the flue gas to produce O3 and O. NO and NO2 contained in the flue gas reacted with the active O and O3 to produce high-valent NOx, such as NO3, N2O5. At last, the mixed slurry of red mud and phosphorus sludge absorbed the high-valent NOx, resulting in the formation of Ca5(PO4)3F along with HNO3. Using phosphorus sludge to produce O3 in the reaction process can reduce the production cost of O3 and achieve waste utilization. Meanwhile, the interaction between red mud and phosphorus sludge can promote phosphorus sludge to produce O3 and remove F- from phosphorus sludge, as well as avoid the problem of secondary pollution. This study should be helpful for red mud and phosphorus sludge utilization and flue gas denitration.

4.
Adv Healthc Mater ; 13(2): e2302175, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37742067

RESUMO

Endometriosis (EM) is a prevalent and debilitating gynecological disorder primarily affecting women of reproductive age. The diagnosis of EM is historically hampered by delays, owing to the absence of reliable diagnostic and monitoring techniques. Herein, it is reported that photoacoustic imaging can be a noninvasive modality for deep-seated EM by employing a hyaluronic-acid-modified polydopamine (PDA@HA) nanoparticle as the contrast agent. The PDA@HA nanoparticles exhibit inherent absorption and photothermal effects when exposed to near-infrared light, proficiently converting thermal energy into sound waves. Leveraging the targeting properties of HA, distinct photoacoustic signals emanating from the periphery of orthotopic EM lesions are observed. These findings are corroborated through anatomical observations and in vivo experiments involving mice with green fluorescent protein-labeled EM lesions. Moreover, the changes in photoacoustic intensity over a 24 h period reflect the dynamic evolution of PDA@HA nanoparticle biodistribution. Through the utilization of a photoacoustic ultrasound modality, in vivo assessments of EM lesion volumes are conducted. This innovative approach not only facilitates real-time monitoring of the therapeutic kinetics of candidate drugs but also obviates the need for the sacrifice of experimental mice. As such, this study presents a promising avenue for enhancing the diagnosis and drug-screening processes of EM.


Assuntos
Endometriose , Indóis , Nanopartículas , Técnicas Fotoacústicas , Polímeros , Feminino , Humanos , Animais , Camundongos , Meios de Contraste , Endometriose/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Distribuição Tecidual , Nanopartículas/uso terapêutico , Fototerapia
5.
Environ Res ; 245: 117970, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38142728

RESUMO

As complex and difficult-to-degrade persistent organic pollutants (POPs), antibiotics have caous damage to the ecological enused serivironment. Because of the difficult degradation of antibiotics, sewage and sludge discharged by hospitals and pharmaceutical enterprises often contain a large number of antibiotic residues. Therefore, the harmless and resourceful treatment of antibiotic sludge is very meaningful. In this paper, amoxicillin was selected as a model compound for antibiotic sludge. Acidified red mud (ARM) was used to degrade antibiotic sludge and produce hydrogen energy carrier formic acid in catalytic wet peroxidation system (CWPO). Based on various characterization analyses, the reaction catalytic mechanism was demonstrated to be the result of the non-homogeneous Fanton reaction interaction between Fe3O4 on the ARM surface and H2O2 in solution. Formic acid is the product of the decarboxylation reaction of amoxicillin and its degradation of various organic acids. The formic acid was produced up to 792.38 mg L-1, under the optimal conditions of reaction temperature of 90 °C, reaction time of 30 min, H2O2 concentration of 20 mL L-1, ARM addition of 0.8 g L-1, pH = 7, and rotor speed of 500 rpm. This research aims to provide some references for promoting red mud utilization in antibiotic sludge degradation.


Assuntos
Antibacterianos , Peróxido de Hidrogênio , Peróxido de Hidrogênio/química , Esgotos , Amoxicilina , Catálise
6.
Nano Lett ; 24(1): 501-510, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38147357

RESUMO

Gram-negative (G-) bacterial infections remain one of the most urgent global health threats, because the distinctive envelope structure hinders the penetration of therapeutics. Here, we showed that a perfluorooctyl bromide nanoemulsion (PFOB NE) uniquely interacts with G- bacteria. After cell envelope attachment, the PFOB can infiltrate the cell and was diffused throughout. In this process, it impaired the membranes by disintegrating phospholipid molecules, enhancing the consequent ultrasonic cavitation to break the envelope. We identified through ultrasound that the NE had remarkable bactericidal effects against various antibiotic-resistant pathogens. Using in situ sterilization, this approach accelerated the recovery of bacteria-infected murine skin wounds. Thus, combining PFOB and ultrasound might be an alternative tool for conquering the growing threat of G- pathogens.


Assuntos
Fluorocarbonos , Hidrocarbonetos Bromados , Camundongos , Animais , Bactérias Gram-Negativas , Fluorocarbonos/química , Antibacterianos/farmacologia , Antibacterianos/química
7.
ACS Appl Mater Interfaces ; 15(27): 32697-32706, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37382894

RESUMO

Day-night photocatalysts that can persistently generate reactive oxygen species (ROS) after ceasing light attracted intensive attention in diverse fields. However, current strategies of combining a photocatalyst and an energy storage material can hardly fulfill the demands, especially in size. We herein present a one-phase sub-5 nm day-night photocatalyst via simply doping Nd, Tm, or Er into YVO4:Eu3+ nanoparticles, efficiently producing ROS in both day and night modes. We demonstrate that the rare earth ions acted as a ROS generator, and Eu3+ and defects contributed to the long persistency. Furthermore, the ultrasmall size led to remarkable bacterial uptake and bactericidal efficacy. Our finding suggests an alternative mechanism of day-night photocatalysts that could be ultrasmall and thus may shed light on disinfection and other applications.

8.
Chem Commun (Camb) ; 59(52): 8123-8126, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37306674

RESUMO

Phototoxicity is an undesirable consequence of photodynamic and most sonodynamic therapies. In the current work, we showed that Er2O3 nanoplates can avoid being cytotoxic when exposed to light and could be an effective sonosensitizer.

9.
J Am Chem Soc ; 144(6): 2455-2459, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-35118859

RESUMO

Exploring materials that can absorb near-infrared (NIR) light to produce reactive oxygen species (ROS) is necessary for many fields. Herein we show that thulium oxide nanoparticles are viable for NIR-stimulated ROS generation. This property may be related to the unique energy levels, large absorption cross section, low fluorescence emission, and ∼10-3 s lifetime of the 3H4 state of Tm ions. We further demonstrate the impact of these nanoparticles on photodynamic therapy (PDT), in which impressive tumor inhibition was recorded after exposure to either a broadband halogen lamp or an 808 nm laser. Our results may provide insight into the areas of photocatalysis, pollution treatment, and fine chemical synthesis.


Assuntos
Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Radiossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/química , Túlio/uso terapêutico , Animais , Linhagem Celular Tumoral , Feminino , Raios Infravermelhos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Camundongos Endogâmicos BALB C , Camundongos Nus , Fotoquimioterapia , Radiossensibilizantes/química , Radiossensibilizantes/efeitos da radiação , Túlio/química , Túlio/efeitos da radiação
10.
ACS Nano ; 15(7): 11953-11969, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34142808

RESUMO

A hypoxic and acidic tumor microenvironment (TME) plays a significant role in cancer development through complex cellular signaling networks, and it is thus challenging to completely eradicate tumors via monotherapy. Here, PEGylated CoFe2O4 nanoflowers (CFP) with multiple enzymatic activities, serving as bioreactors responsive to TME cues, were synthesized via a typical solvothermal method for augmented sonodynamic therapy (SDT) and chemodynamic therapy (CDT) with elicitation of robust immune response. The CFP occupying multivalent elements (Co2+/3+, Fe2+/3+) exhibited strong Fenton-like and catalase-like activity. In another aspect, CFP itself is a brand-new sonosensitizer for high-performance SDT based on ultrasound-triggered electron (e-)/hole (h+) pair separation from the energy band with promptness and high efficiency. With efficient enrichment in tumorous tissue as revealed by magnetic resonance imaging, CPF could generate •OH for CDT relying on Fenton-like reactions. Moreover, catalase-mimicking CFP could react with endogenous H2O2 to generate molecular oxygen, and high O2 level may promote the production of 1O2 for SDT. What's more, the reactive oxygen species obtained from combined SDT/CDT could efficiently trigger immunogenic cell death through a synergistic therapy based on the elicitation of antitumor immunity with the aid of an immune checkpoint blockade for the sake of suppressing primary and distant tumors as well as lung metastasis. Taken together, this paradigm delivers useful insights for developing in-coming nanocomposites based on cobalt ferrite for cancer theranostics.


Assuntos
Peróxido de Hidrogênio , Neoplasias , Humanos , Catalase , Peróxido de Hidrogênio/farmacologia , Linhagem Celular Tumoral , Terapia Combinada , Microambiente Tumoral , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Imunidade
11.
J Mater Chem B ; 9(17): 3677-3688, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-33949613

RESUMO

Silk fibroin (SF), derived from Bombyx mori, is a category of fibrous protein with outstanding potential for applications in the biomedical and biotechnological fields. In spite of its many advantageous properties, the exploration of SF as a versatile nanodrug precursor for tumor therapy has still been restricted in recent years. Herein, a multifunctional SF-derived nanoplatform was facilely developed via encapsulating the photosensitizer chlorin e6 (Ce6) into MnO2-capped SF nanoparticles (NPs). SF@MnO2 nanocarriers were synthesized through a surface crystallization technique, using SF as a reductant and sacrificial template. Afterwards, Ce6 was covalently incorporated into the loose structure of the SF@MnO2 nanocarrier on the basis of adsorption to abundant peptide-binding sites. To modulate the tumor microenvironment (TME), SF@MnO2/Ce6 (SMC) NPs were capable of catalyzing the decomposition of H2O2 into O2, which can be converted into cytotoxic reactive oxygen species (ROS) during photodynamic therapy (PDT). Moreover, the MnO2 component was able to oxidize intracellular glutathione (GSH) into non-reducing glutathione disulfide (GSSG), and the consumption of GSH could significantly protect the local ROS from being reduced, which further augmented the therapeutic outcome of PDT. Via another angle, SMC NPs can produce strong hyperthermia under near-infrared (NIR) light activation, which was highly desirable for efficient photothermal therapy (PTT). Both in vitro and in vivo studies demonstrated the intense tumor inhibitory effects as a result of augmented PTT/PDT mediated by SMC NPs. We believe that this study may provide useful insights for employing SF-based nanocomposites for more medical applications in the near future.


Assuntos
Antineoplásicos/química , Fibroínas/química , Compostos de Manganês/química , Nanopartículas/química , Óxidos/química , Fármacos Fotossensibilizantes/química , Porfirinas/química , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Clorofilídeos , Cristalização , Feminino , Glutationa/química , Dissulfeto de Glutationa/química , Humanos , Peróxido de Hidrogênio/química , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais , Oxirredução , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/química , Propriedades de Superfície
12.
Theranostics ; 11(1): 107-116, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391464

RESUMO

Background: Reactive oxygen species (ROS), as a category of highly reactive molecules, are attractive for eliminating tumor cells in situ. However, the intrinsic tumor microenvironment (TME) always compromises treatment efficacy. In another aspect, silk fibroin (SF), as a category of natural biomacromolecules, is highly promising for synthesis of metallic nanocrystals via biomineralization. Methods: As a proof-of-concept study, AuPt bimetallic nanozyme derived from bioinspired crystallization of chloroauric acid and chloroplatinic acid was facilely developed in the presence of silk fibroin (SF). Antitumor effects caused by the as-synthesized AuPt@SF (APS) nanozyme were demonstrated in 4T1 tumor cells in vitro and xenograft tumor models in vivo. Results: APS nanozyme can decompose glucose to constantly supply H2O2 and deplete intracellular glutathione (GSH). APS nanozyme can simultaneously convert adsorbed O2 and endogenic H2O2 into superoxide radicals (•O2-) and hydroxyl radical (•OH), respectively, upon highly efficient catalytic reaction. Subsequently, these cytotoxic ROS cause irreversible damage to the cell membrane, nucleic acid and mitochondria of tumors. Upon fluorescence/photoacoustic (FL/PA)-imaging guidance, remarkable tumor damage based on the current nanoplatform was confirmed in vivo. Conclusion: The objective of our investigation is to supply more useful insights on the development of SF-based nanocatalysts, which are specifically responsive to TME for extremely efficient tumor theranostics.


Assuntos
Neoplasias da Mama/metabolismo , Fibroínas , Ouro/farmacologia , Nanopartículas Metálicas , Platina/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Biomineralização , Catálise , Linhagem Celular Tumoral , Cloretos , Feminino , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Compostos de Ouro , Peróxido de Hidrogênio/metabolismo , Radical Hidroxila/metabolismo , Técnicas In Vitro , Camundongos , Imagem Óptica , Técnicas Fotoacústicas , Compostos de Platina , Estudo de Prova de Conceito , Espécies Reativas de Oxigênio/metabolismo , Superóxidos/metabolismo
13.
J Mater Chem B ; 8(34): 7766-7776, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32744285

RESUMO

Traditional techniques for the synthesis of nickel sulfide (NiS) nanoparticles (NPs) always present drawbacks of morphological irregularity, non-porous structure and poor long-term stability, which are extremely unfavorable for establishing effective therapeutic agents. Here, a category of hollow mesoporous NiS (hm-NiS) NPs with uniform spherical structure and good aqueous dispersity were innovatively developed based on a modified solvothermal reaction technique. Upon the successful synthesis of hm-NiS NPs, dopamine was seeded and in situ polymerized into polydopamine (PDA) on the NP surface, followed by functionalization with thiol-polyethylene glycol (SH-PEG) and encapsulation of the chemotherapeutic drug, doxorubicin (DOX), to form hm-NiS@PDA/PEG/DOX (NiPPD) NPs. The resultant NiPPD NPs exhibited a decent photothermal response and stability, attributed to the optical absorption of the hm-NiS nanocore and PDA layer in the near-infrared (NIR) region. Furthermore, stimulus-responsive drug release was achieved under both acidic pH conditions and NIR laser irradiation, owing to the protonation of -NH2 groups in the DOX molecules and local thermal shock, respectively. Lastly, a strong combinatorial photothermal-chemotherapeutic effect was demonstrated for tumor suppression with minimal systemic toxicity in vivo. Collectively, this state-of-the-art paradigm may provide useful insights to deepen the application of hm-NiS NPs for disease management and precision medicine.


Assuntos
Nanomedicina/métodos , Nanopartículas/química , Níquel/química , Fototerapia/métodos , Linhagem Celular , Técnicas de Química Sintética , Terapia Combinada , Doxorrubicina/química , Humanos , Indóis/química , Níquel/uso terapêutico , Polietilenoglicóis/química , Polímeros/química , Porosidade
14.
Biomaterials ; 257: 120279, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32763613

RESUMO

Chemodynamic therapy (CDT), an emerging therapeutic strategy, has been recently exploited for in situ treatment through Fenton or Fenton-like reactions to generate cytotoxic reactive oxygen species (ROS). However, current systems rely significantly on the high local oxygen levels and strongly acidic conditions (pH = 3.0-5.0). Simultaneously, the produced ROS can be rapidly consumed by intracellular glutathione (GSH) in the electron transport chain. Herein, an original and biomimetic CoO@AuPt nanocatalyst was prepared based on the assembly of Au and Pt nanoparticles (NPs) on the surface of hollow CoO nanocapsules. The as-synthesized nanozyme exhibits extremely high stability under physiological conditions, whereas it undergoes spontaneous disintegration in the unique tumor microenvironment (TME). Subsequently, the decomposition products can catalyze a cascade of biochemical reactions to produce abundant ROS without any external stimuli. Thus, the present nanoplatform can increase intracellular ROS levels through continuous supply of H2O2, relief of local hypoxia and depletion of GSH, which result in remarkable and specific tumor damage both in vitro and in vivo. The findings of this study highlight the promising potential of CoO@AuPt nanocatalyst as a TME-responsive CDT nanomagnet for highly efficient tumor therapy.


Assuntos
Antineoplásicos , Microambiente Tumoral , Antineoplásicos/farmacologia , Biomimética , Linhagem Celular Tumoral , Peróxido de Hidrogênio/farmacologia
15.
J Mater Chem B ; 7(47): 7515-7524, 2019 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-31714572

RESUMO

Microneedles are primarily designed for enhancing transdermal drug delivery in a minimally invasive manner. In particular, coated microneedles have attracted increasing attention due to the resulting mode of rapid and highly efficient drug administration. In this study, we developed a novel gelatin/sucrose film-coated poly(ethylene glycol)diacrylate (PEGDA) microneedle patch, which can effectively improve the skin permeability of therapeutic drugs and realize convenient and efficient drug administration. A simple and reliable technique was proposed to produce uniform film coatings on microneedles at room temperature. After introducing a prepolymer solution into the mold cavity, a film-coated microneedle patch was fabricated via a photo-induced polymerization process. Four categories of molecular models, including rhodamine B (RhB), bovine serum albumin (BSA), doxorubicin (DOX) and indocyanine green (ICG), were encapsulated into the gelatin/sucrose film to evaluate their transdermal delivery and therapeutic effects both in vitro and in vivo. The presented methodology represents a facile technique for rapid formation of film-coated microneedles for efficient transdermal delivery of small molecular drugs and large proteins.


Assuntos
Portadores de Fármacos/química , Gelatina/química , Polietilenoglicóis/química , Sacarose/química , Animais , Materiais Biocompatíveis/química , Bovinos , Doxorrubicina/química , Doxorrubicina/metabolismo , Liberação Controlada de Fármacos , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Microinjeções , Agulhas , Rodaminas/química , Rodaminas/metabolismo , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Pele/metabolismo , Absorção Cutânea
16.
Theranostics ; 9(21): 6314-6333, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31534553

RESUMO

Regenerated silk fibroin (SF) is a type of natural biomacromolecules with outstanding biocompatibility and biodegradability. However, stimulus-responsive SF-based nanocomplex has seldom been reported for application in tumor diagnosis and therapy. Methods: As a proof-of-concept study, a multifunctional SF@MnO2 nanoparticle-based platform was strategically synthesized using SF as a reductant and a template via a biomineralization-inspired crystallization process in an extremely facile way. Because of their mesoporous structure and abundant amino and carboxyl terminal residues, SF@MnO2 nanoparticles were co-loaded with a photodynamic agent indocyanine green (ICG) and a chemotherapeutic drug doxorubicin (DOX) to form a SF@MnO2/ICG/DOX (SMID) nanocomplex. Results: The obtained product was highly reactive with endogenous hydrogen peroxide (H2O2) in tumor microenvironment, which was decomposed into O2 to enhance tumor-specific photodynamic therapy (PDT). Moreover, SMID nanocomplex produced a strong and stable photothermal effect upon near-infrared (NIR) irradiation for photothermal therapy (PTT) owing to the distinct photothermal response of SF@MnO2 and stably conjugated ICG. The concurrent NIR fluorescence and magnetic resonance (MR) imaging in vivo both indicated effective tumor-specific enrichment of SMID nanoparticles via enhanced permeability and retention (EPR) effect. Animal studies further verified that SMID nanoparticles remarkably improved tumor inhibitive efficacy through combination PTT/PDT/chemotherapy with minimal systemic toxicity or adverse effect. Conclusion: This study demonstrated the promising potential of SF-based nanomaterial to address some of the key challenges in cancer therapy due to unfavorable tumor microenvironment for drug delivery.


Assuntos
Doxorrubicina/administração & dosagem , Fibroínas/química , Compostos de Manganês/química , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Óxidos/química , Animais , Biomineralização , Terapia Combinada , Cristalização , Feminino , Humanos , Peróxido de Hidrogênio/química , Verde de Indocianina/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/tratamento farmacológico , Imagem Óptica , Fotoquimioterapia , Distribuição Tecidual , Microambiente Tumoral
17.
Biomed Microdevices ; 21(3): 58, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227909

RESUMO

Traditional immunomagnetic assays for the isolation and recovery of circulating tumor cells (CTCs) usually require sophisticated device or intense magnetic field to simultaneously achieve high capture efficiency and high throughout. In this study, a simple microfluidic chip featured with nanoroughened channel substrate was developed for effectively capture and release of CTCs based on an immunomagnetic chip-based approach. The nanoroughened substrate aims to increase the cell-surface contact area, facilitate the immobilization of magnet particles (MPs) and accommodate cell attachment tendency. Hep3B tumor cells were firstly conjugated with MPs that were functionalized with anti-EpCAM. Comparing with the flat channel, MPs modified tumor cells can be more effectively captured on nanoroughened substrate at the presence of the magnetic field. Upon the removal of magnetic field, these captured cells can be released from the device and collected for further analysis. Under the optimum operating conditions, the capture efficiency of tumor cells was obtained as high as ~90% with a detection limit of 10 cell per mL. Additionally, recovery rates of trapped tumor cells at various densities all exceeded 90% and their biological potencies were well retained by investigating the cell attachment and proliferation. Therefore, the present approach may potentially be used in clinical CTC analysis for cancer diagnosis and prognosis as well as the fundamental understanding of tumor metastasis.


Assuntos
Dimetilpolisiloxanos/química , Separação Imunomagnética/instrumentação , Nanoestruturas/química , Células Neoplásicas Circulantes/patologia , Adesão Celular , Linhagem Celular Tumoral , Proliferação de Células , Molécula de Adesão da Célula Epitelial/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Células Neoplásicas Circulantes/metabolismo , Propriedades de Superfície , Fatores de Tempo
18.
Nanoscale ; 11(12): 5717-5731, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30865744

RESUMO

Hollow mesoporous structures with interior cavities and expanded surface area have attracted considerable interest as drug delivery systems. In this study, a multifunctional nanotheranostic agent was developed by conjugating indocyanine green (ICG) and loading doxorubicin (DOX) onto the surfaces or within the cavities of hollow mesoporous Prussian blue (HMPB) nanoparticles, known as HMPB@PEI/ICG/DOX or simply HPID NPs, which were investigated as phototheranostic agents for in vivo fluorescence imaging and light-induced chemotherapy, photothermal therapy (PTT) and photodynamic therapy (PDT). These original HPID NPs exhibited strong near infrared (NIR) absorbance, reactive oxygen species (ROS) yield, and controlled chemotherapeutic drug release behavior. After intravenous injection of HPID NPs, highly efficient solid tumor ablation effects were observed in 4T1 tumor-bearing mouse models under NIR laser irradiation. Additionally, there was insignificant low-term toxicity or damage to normal tissues, as evidenced by histopathological and hemocompatibility analyses, suggesting that this agent has reliable biosafety for systemic applications. Taken together, the results of this study suggest that HPID NPs can produce tumor-specific and stimuli-triggered theranostic effects under tri-modal combination therapy. These HPID NPs advantageously provide traceable accumulation and activation and therefore could be a capable mediator in nanomedicines for eliminating solid tumors.


Assuntos
Antibióticos Antineoplásicos/química , Doxorrubicina/química , Ferrocianetos/química , Verde de Indocianina/química , Nanopartículas/química , Animais , Antibióticos Antineoplásicos/metabolismo , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Porosidade , Distribuição Tecidual
19.
Biomacromolecules ; 20(3): 1334-1345, 2019 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-30703318

RESUMO

Polymeric microneedles have attracted increasing attention as a minimally invasive platform for delivering drugs or vaccines in a more patient-friendly manner. However, traditional microfabrication techniques using negative molds with needle-shaped cavities usually require cumbersome centrifugation and vacuum degassing processes, which have restricted the scaled-up mass production of polymeric microneedles. Herein, a novel polydimethylsiloxane (PDMS)-based negative mold with cavities packed with silk fibroin scaffold is developed for rapid fabrication of polymeric microneedles, which comprise primarily the composition of poly(ethylene glycol) diacrylate (PEGDA) and sucrose as the needle matrix. Fibroin scaffolds can instantly adsorb prepolymer solution due to capillary force, and subsequently initiate the formation of microneedles via photoinduced polymerization. Based on three types of model drugs, including Rhodamine B (RhB), indocyanine green (ICG), and doxorubicin (DOX), the fabricated PEGDA/sucrose microneedles can realize effective transdermal delivery and controllable release of therapeutic molecules by regulating the sucrose content. The presented method provides a simple strategy for quick fabrication of polymeric microneedles toward transdermal drug delivery applications.


Assuntos
Administração Cutânea , Sistemas de Liberação de Medicamentos , Fibroínas/química , Agulhas , Polietilenoglicóis/química , Sacarose/química , Animais , Doxorrubicina/administração & dosagem , Células Endoteliais da Veia Umbilical Humana , Humanos , Verde de Indocianina/administração & dosagem , Camundongos , Porosidade , Rodaminas/administração & dosagem
20.
ACS Appl Mater Interfaces ; 11(1): 417-429, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30537815

RESUMO

Environmental stimuli, including pH, light, and temperature, have been utilized for activating controlled drug delivery to achieve efficient antitumor therapeutics while minimizing undesirable side effects. In this study, a multifunctional nanoplatform based on hollow mesoporous copper sulfide nanoparticles (H-CuS NPs) was developed by loading the interior cavity of the NPs with a drug-loaded phase-change material (PCM, 1-tetradecanol). Doxorubicin (DOX) and chlorin e6 (Ce6) were selected as the model chemotherapeutic drug and photosensitizer, respectively, which were encapsulated in H-CuS NPs via the PCM to form H-CuS@PCM/DOX/Ce6 (HPDC) NPs. When exposed to near infrared laser irradiation, this nanocomplex could produce a strong photothermic effect and thus induce the controlled release of DOX and Ce6 from the melting PCM. Subsequently, the DOX-mediated chemotherapeutic effect and Ce6-mediated photodynamic effect further contributed to enhanced tumor eradication. The efficacy of this multimodal cancer treatment combining chemo-, photothermal, and photodynamic therapies was systematically evaluated both in vitro and in vivo using a 4T1 mouse mammary tumor cell line and a mouse model bearing breast cancer. Moreover, this nanoplatform exhibited minimal systemic toxicity and good hemocompatibility and may provide an effective strategy for the delivery of multiple therapeutic agents and application of multimodal cancer treatments.


Assuntos
Neoplasias da Mama , Doxorrubicina , Sistemas de Liberação de Medicamentos , Hipertermia Induzida , Neoplasias Mamárias Experimentais , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Clorofilídeos , Cobre/química , Cobre/farmacocinética , Cobre/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Feminino , Raios Infravermelhos , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/terapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Porfirinas/farmacocinética , Porfirinas/farmacologia , Sulfetos , Ensaios Antitumorais Modelo de Xenoenxerto
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