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1.
Small ; 20(26): e2308861, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38372029

RESUMO

The anabolism of tumor cells can not only support their proliferation, but also endow them with a steady influx of exogenous nutrients. Therefore, consuming metabolic substrates or limiting access to energy supply can be an effective strategy to impede tumor growth. Herein, a novel treatment paradigm of starving-like therapy-triple energy-depleting therapy-is illustrated by glucose oxidase (GOx)/dc-IR825/sorafenib liposomes (termed GISLs), and such a triple energy-depleting therapy exhibits a more effective tumor-killing effect than conventional starvation therapy that only cuts off one of the energy supplies. Specifically, GOx can continuously consume glucose and generate toxic H2O2 in the tumor microenvironment (including tumor cells). After endocytosis, dc-IR825 (a near-infrared cyanine dye) can precisely target mitochondria and exert photodynamic and photothermal activities upon laser irradiation to destroy mitochondria. The anti-angiogenesis effect of sorafenib can further block energy and nutrition supply from blood. This work exemplifies a facile and safe method to exhaust the energy in a tumor from three aspects and starve the tumor to death and also highlights the importance of energy depletion in tumor treatment. It is hoped that this work will inspire the development of more advanced platforms that can combine multiple energy depletion therapies to realize more effective tumor treatment.


Assuntos
Glucose Oxidase , Lipossomos , Sorafenibe , Lipossomos/química , Humanos , Glucose Oxidase/metabolismo , Glucose Oxidase/química , Animais , Sorafenibe/farmacologia , Linhagem Celular Tumoral , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Metabolismo Energético , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/química , Indóis
2.
Nano Lett ; 23(10): 4683-4692, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-36912868

RESUMO

The oral delivery of probiotics is commonly adopted for intestinal disease treatments in clinical settings; however, the probiotics suffer from a strong acidic attack in the gastric area and the low-efficiency intestinal colonization of naked probiotics. Coating living probiotics with synthetic materials has proven effective in enabling the adaption of bacteria to gastrointestinal environments, which, unfortunately, may shield the probiotics from initiating therapeutic responses. In this study, we report a copolymer-modified two-dimensional H-silicene nanomaterial (termed SiH@TPGS-PEI) that can facilitate probiotics to adapt to diverse gastrointestinal microenvironments on-demand. Briefly, SiH@TPGS-PEI electrostatically coated on the surface of probiotic bacteria helps to resist erosive destruction in the acidic stomach and spontaneously degrades by reacting with water to generate hydrogen, an anti-inflammatory gas in response to the neutral/weakly alkaline intestinal environment, thus exposing the probiotic bacteria for colitis amelioration. This strategy may shed new light on the development of intelligent self-adaptive materials.


Assuntos
Colite , Probióticos , Humanos , Intestinos , Bactérias , Probióticos/metabolismo , Probióticos/uso terapêutico
3.
J Am Chem Soc ; 145(24): 13249-13260, 2023 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-37285166

RESUMO

Iodine, as a typical haloid element in group VIIA, has been extensively applied as antiseptics clinically, thanks to its effective and wide-spectrum antimicrobial activity against bacteria, fungi, and viruses. Nevertheless, current iodic sterilizing agents are still limited to topical applications such as instrument sterilization and treatments of skin or mucous membrane infection due to its unsatisfactory stability and biocompatibility. Here, we propose an emerging two-dimensional iodine nanomaterial (noted as iodinene) for the treatment of infection diseases in vivo. Iodinene nanosheets were fabricated by a facile and environmentally friendly approach via sonication-assisted liquid exfoliation, which present an intriguing layered structure and negligible toxicity. The as-synthesized iodinene would experience an in situ allotropic transformation spontaneously to release active HIO and I2 molecules by reacting with H2O2 in the infectious microenvironment. By the in situ production of active HIO and I2 molecules via allotropic transformation, iodinene presents enhanced antibacterial efficacy against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. In vivo outcome demonstrates the desirable antibacterial efficacy of iodinene in treating bacterial wound infection and pneumonia. This study thus offers an alternative to conventional sterilizing agents against hard-to-treat bacterial infections.


Assuntos
Anti-Infecciosos Locais , Infecções Bacterianas , Iodo , Humanos , Iodo/farmacologia , Peróxido de Hidrogênio , Antibiose , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Bactérias
4.
J Am Chem Soc ; 144(31): 14195-14206, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35830228

RESUMO

As an emerging therapeutic gas, hydrogen (H2) is gifted with excellent biosafety, high tissue permeability, and radical-trapping capacity and is extensively considered as a highly promising antioxidant in clinics. However, a facile and effective strategy of H2 production for major inflammatory disease treatments is still lacking. In this study, by a facile wet-chemical exfoliation synthesis, a hydrogen-terminated silicon nanosheet (H-silicene) has been synthesized, which can favorably react with environmental water to generate H2 rapidly and continuously without any external energy input. Furthermore, theoretical calculations were employed to reveal the mechanism of enhanced H2 generation efficacy of H-silicene nanosheets. The as-synthesized H-silicene has been explored as a flexible hydrogen gas generator for efficient antioxidative stress application for the first time, which highlights a promising prospect of this two-dimensional H-silicene nanomaterial for acute inflammatory treatments by on-demand H2 production-enabled reactive oxygen species scavenging. This study provides a novel and efficient modality for nanomaterial-mediated H2 therapy.


Assuntos
Silício , Água , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Hidrogênio , Estresse Oxidativo , Espécies Reativas de Oxigênio
5.
Anal Chem ; 94(10): 4243-4251, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35235297

RESUMO

The discrimination between dead and live cells is crucial for cell viability evaluation. Carbon dots (CDs), with advantages like simple and cost-effective synthesis, excellent biocompatibility, and high photostability, have shown potential for realizing selective live/dead cell staining. However, most of the developed CDs with the live/dead cell discrimination capacity usually have low photoluminescence quantum yields (PLQYs) and excitation wavelength-dependent fluorescence emission (which can cause fluorescence overlap with other fluorescent probes and make dual-color live/dead staining impossible), and hence, developing ultrabright CDs with excitation wavelength-independent fluorescence emission property for live/dead cell discrimination becomes an important task. Here, using a one-pot hydrothermal method, we prepared ultrasmall (∼1.6 nm), ultrabright (PLQY: ∼78%), and excitation wavelength-independent sulfur-doped carbon dots (termed S-CDs) using rose bengal and 1,4-dimercaptobenzene as raw materials and demonstrated that the S-CDs could rapidly (∼5 min) and accurately distinguish dead cells from live ones for almost all the cell types including bacterial, fungal, and animal cells in a wash-free manner. We confirmed that the S-CDs could rapidly pass through the dead cell surfaces to enter the interior of the dead cells, thus visualizing these dead cells. In contrast, the S-CDs could not enter the interior of live cells and thus could not stain these live cells. We further verified that the S-CDs presented better biocompatibility and higher photostability than the commercial live/dead staining dye propidium iodide, ensuring its bright application prospect in cell imaging and cell viability assessment. Overall, this work develops a type of CDs capable of realizing the live/dead cell discrimination of almost all the cell types (bacterial, fungal, and animal cells), which has seldom been achieved by other fluorescent nanoprobes.


Assuntos
Carbono , Pontos Quânticos , Animais , Corantes Fluorescentes , Nitrogênio , Pontos Quânticos/toxicidade , Rosa Bengala , Enxofre
6.
Small ; 18(46): e2203260, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36333101

RESUMO

Developing a universal nanoplatform for efficient delivery of various drugs to target sites is urgent for overcoming various biological barriers and realizing combinational cancer treatment. Nanogels, with the advantages of both hydrogels and nanoparticles, may hold potential for addressing the above issue. Here, a dual-responsive nanogel platform (HPC nanogel) is constructed using ß-cyclodextrin-conjugated hyaluronic acid (HA-ßCD), polyethyleneimine (PEI), and cisplatin. HA-ßCD and PEI compose the skeleton of the nanogel, and cisplatin molecules provide the junctions inside the skeleton, thus affording a multiple interactions-based nanogel. Besides, HA endows the nanogel with hyaluronidase (HAase)-responsiveness, and cisplatin guarantees the glutathione (GSH)-responsive ability, which make the nanogel a dual-responsive platform that can degrade and release the loaded drugs when encountering HAase or GSH. Additionally, the HPC nanogel possesses excellent small-molecule drug and protein loading and intracellular delivery capabilities. Especially, for proteins, their intracellular delivery via nanogels is not hindered by serum proteins, and the enzymes delivered into cells still maintain their catalytic activities. Furthermore, the nanogel can codeliver different cargoes to achieve "cocktail" chemotherapeutic efficacy and realize combination cancer therapy. Overall, the HPC nanogel can serve as a multifunctional platform capable of delivering desired drugs to treat cancer or other diseases.


Assuntos
Neoplasias , Platina , Nanogéis , Cisplatino/uso terapêutico , Polietilenoimina , Polietilenoglicóis , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico
7.
Chem Soc Rev ; 50(10): 6240-6277, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34027939

RESUMO

Systematically dissecting the molecular basis of the cell surface as well as its related biological activities is considered as one of the most cutting-edge fields in fundamental sciences. The advent of various advanced cell imaging techniques allows us to gain a glimpse of how the cell surface is structured and coordinated with other cellular components to respond to intracellular signals and environmental stimuli. Nowadays, cell surface-related studies have entered a new era featured by a redirected aim of not just understanding but artificially manipulating/remodeling the cell surface properties. To meet this goal, biologists and chemists are intensely engaged in developing more maneuverable cell surface labeling strategies by exploiting the cell's intrinsic biosynthetic machinery or direct chemical/physical binding methods for imaging, sensing, and biomedical applications. In this review, we summarize the recent advances that focus on the visualization of various cell surface structures/dynamics and accurate monitoring of the microenvironment of the cell surface. Future challenges and opportunities in these fields are discussed, and the importance of cell surface-based studies is highlighted.


Assuntos
Microscopia de Fluorescência , Coloração e Rotulagem/métodos , Animais , Membrana Celular/química , Membrana Celular/metabolismo , Corantes Fluorescentes/química , Humanos , Microdomínios da Membrana/química , Microdomínios da Membrana/metabolismo , Engenharia Metabólica , Polissacarídeos/química , Polissacarídeos/genética , Polissacarídeos/metabolismo , Propriedades de Superfície
8.
Zhongguo Zhong Yao Za Zhi ; 47(13): 3409-3424, 2022 Jul.
Artigo em Zh | MEDLINE | ID: mdl-35850791

RESUMO

The Chinese medicinal herb Mahuang is herbaceous stem of Ephedra sinica, E. intermedia, or E. equisetina(Family, Ephedraceae). In China, Mahuang has been used, all the way over a millennium, as a key component herb of many herbal medicines for management of epidemics of acute respiratory illness and is also used in officially recommended herbal medicines for COVID-19. Mahuang is the first-line medicinal herb for cold and wheezing and also an effective diuretic herb for edema. However, Mahuang can also exert significant adverse effects. The key to safety and effectiveness is rational and precise use of the herb. In this review article, we comprehensively summarize chemical composition of Mahuang and associated differences in pharmacognosy, pharmacodynamics and pharmacokinetics of Mahuang compounds, along with the adverse effects of Mahuang compounds and products. Based on full understanding of how Mahuang is used in Chinese traditional medicine, systematic research on Mahuang in line with contemporary standards of pharmaceutical sciences will facilitate promoting Chinese herbal medicines to become more efficient in management of epidemic illnesses, such as COVID-19. To this end, we recommend research on Mahuang of two aspects, i.e., pharmacological investigation for its multicompound-involved therapeutic effects and toxicological investigation for clinical manifestation of the adverse effects, chemicals responsible for the adverse effects, and conditions for safe use of the herb and the herb-containing medicines.


Assuntos
Tratamento Farmacológico da COVID-19 , Medicamentos de Ervas Chinesas , Ephedra sinica , Ephedra , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Ephedra sinica/química , Efedrina/química , Humanos , Plantas
9.
Small ; 17(34): e2100753, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34259382

RESUMO

Tumor vasculature has long been considered as an extremely valuable therapeutic target for cancer therapy, but how to realize controlled and site-specific drug release in tumor blood vessels remains a huge challenge. Despite the widespread use of nanomaterials in constructing drug delivery systems, they are suboptimal in principle for meeting this demand due to their easy blood cell adsorption/internalization and short lifetime in the systemic circulation. Here, natural red blood cells (RBCs) are repurposed as a remote-controllable drug vehicle, which retains RBC's morphology and vessel-specific biodistribution pattern, by installing photoactivatable molecular triggers on the RBC membrane via covalent conjugation with a finely tuned modification density. The molecular triggers can burst the RBC vehicle under short and mild laser irradiation, leading to a complete and site-specific release of its payloads. This cell-based vehicle is generalized by loading different therapeutic agents including macromolecular thrombin, a blood clotting-inducing enzyme, and a small-molecule hypoxia-activatable chemodrug, tirapazamine. In vivo results demonstrate that the repurposed "anticancer RBCs" exhibit long-term stability in systemic circulation but, when tumors receive laser irradiation, precisely releases their cargoes in tumor vessels for thrombosis-induced starvation therapy and local deoxygenation-enhanced chemotherapy. This study proposes a general strategy for blood vessel-specific drug delivery.


Assuntos
Liberação Controlada de Fármacos , Reposicionamento de Medicamentos , Vasos Sanguíneos , Eritrócitos , Distribuição Tecidual
10.
Small ; 15(11): e1804575, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30761748

RESUMO

Herein, water-dispersible carbon nano-onion clusters (CNOCs) with an average hydrodynamic size of ≈90 nm are prepared by simply sonicating candle soot in a mixture of oxidizing acid. The obtained CNOCs have high photothermal conversion efficiency (57.5%), excellent aqueous dispersibility (stable in water for more than a year without precipitation), and benign biocompatibility. After polyethylenimine (PEI) and poly(ethylene glycol) (PEG) modification, the resultant CNOCs-PEI-PEG have a high photothermal conversion efficiency (56.5%), and can realize after-wash photothermal cancer cell ablation due to their ultrahigh cellular uptake (21.3 pg/cell), which is highly beneficial for the selective ablation of cancer cells via light-triggered intracellular heat generation. More interestingly, the cellular uptake of CNOCs-PEI-PEG is so high that the internalized nanoagents can be directly observed under a microscope without fluorescent labeling. Besides, in vivo experiments reveal that CNOCs-PEI-PEG can be used for photothermal/photoacoustic dual-modal imaging-guided photothermal therapy after intravenous administration. Furthermore, CNOCs-PEI-PEG can be efficiently cleared from the mouse body within a week, ensuring their excellent long-term biosafety. To the best of the authors' knowledge, the first example of using candle soot as raw material to prepare water-dispersible onion-like carbon nanomaterials for cancer theranostics is represented herein.


Assuntos
Carbono/química , Diagnóstico por Imagem , Hipertermia Induzida , Nanoestruturas/química , Neoplasias/terapia , Fototerapia , Fuligem/química , Água/química , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Nanoestruturas/ultraestrutura , Técnicas Fotoacústicas , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoimina/síntese química , Polietilenoimina/química , Temperatura
11.
Langmuir ; 35(44): 14324-14331, 2019 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-31580079

RESUMO

Photodynamic therapy is a promising approach for fighting bacterial infections because it can induce few side effects, develop no drug resistance, and realize precise treatment. However, most photosensitizers (PSs) have the disadvantages of poor water-solubility, severe self-quenching, and potential toxicity. Here, the cationic polymer polyethyleneimine (PEI) was used to prepare a cholesterol- and chlorin e6 (Ce6, a common PS)-conjugated compound via the carboxyl-amine reaction or the acyl chloride-amine reaction (abbreviated as Chol-PEI-Ce6). The as-prepared Chol-PEI-Ce6 molecules can self-assemble into close-to-spherical nanoparticles (NPs) with an average diameter of ∼15 nm and can bind to the bacterial surfaces via the synergistic hydrophobic insertion of the cholesterol moieties and electrostatic interaction between the cationic amine groups of PEI and the bacterial surfaces. Upon light irradiation, the NPs can effectively inactivate both Gram-positive and Gram-negative bacteria. Besides, the interaction between Chol-PEI-Ce6 NPs and bacteria markedly enhances the production of intracellular reactive oxygen species after light irradiation, which may account for the excellent antibacterial performance of the NPs. More importantly, the NPs possess negligible dark cytotoxicity and good hemocompatibility. Therefore, the present work may have strong implications for developing novel antibacterial agents to fight against bacterial infections.


Assuntos
Antibacterianos/química , Colesterol/química , Fotoquimioterapia/métodos , Polietilenoimina/química , Espécies Reativas de Oxigênio/metabolismo
12.
J Am Chem Soc ; 140(11): 4062-4070, 2018 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-29406728

RESUMO

Research on nanomedicines has rapidly progressed in the past few years. However, due to the limited size of nuclear pores (9-12 nm), the nuclear membrane remains a difficult barrier to many nucleus-targeting agents. Here, we report the development of a general platform to effectively deliver chemical compounds such as drug molecules or nanomaterials into cell nuclei. This platform consists of a polyamine-containing polyhedral oligomeric silsesquioxane (POSS) unit, a hydrophilic polyethylene glycol (PEG) chain, and the photosensitizer rose bengal (RB), which can self-assemble into nanoparticles (denoted as PPR NPs). Confocal fluorescence imaging showed that PPR NPs mainly located in lysosomes after cellular internalization. After mild light irradiation, however, PPR NPs effectively disrupted lysosomal structures by singlet oxygen (1O2) oxidation and substantially accumulated on nuclear membranes, which enabled further disruption of the membrane integrity and promoted their final nuclear entry. Next, we selected two chemotherapeutic agents (10-hydroxycamptothecine and docetaxel) and a fluorescent dye (DiD) as payloads of PPR NPs and successfully demonstrated that this nanocarrier could efficiently deliver them into cell nuclei in a light-controlled manner. In addition to molecular compounds, we have also demonstrated that PPR NPs could facilitate the nuclear entry of nanomaterials, including Prussian blue NPs as well as gold nanorods. Compared to traditional strategies for nuclear delivery, this highly controllable nanoplatform avoids complicated modification of nucleus-targeting ligands and is generally applicable to both molecular compounds and nanomaterials.


Assuntos
Núcleo Celular/química , Sistemas de Liberação de Medicamentos , Luz , Nanopartículas/química , Camptotecina/análogos & derivados , Camptotecina/química , Camptotecina/farmacologia , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Docetaxel , Corantes Fluorescentes/química , Humanos , Compostos de Organossilício/química , Tamanho da Partícula , Poliaminas/química , Polietilenoglicóis/química , Rosa Bengala/química , Taxoides/química , Taxoides/farmacologia
13.
Nat Commun ; 15(1): 5147, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886343

RESUMO

Bacteria-mediated cancer therapeutic strategies have attracted increasing interest due to their intrinsic tumor tropism. However, bacteria-based drugs face several challenges including the large size of bacteria and dense extracellular matrix, limiting their intratumoral delivery efficiency. In this study, we find that hyperbaric oxygen (HBO), a noninvasive therapeutic method, can effectively deplete the dense extracellular matrix and thus enhance the bacterial accumulation within tumors. Inspired by this finding, we modify Escherichia coli Nissle 1917 (EcN) with cypate molecules to yield EcN-cypate for photothermal therapy, which can subsequently induce immunogenic cell death (ICD). Importantly, HBO treatment significantly increases the intratumoral accumulation of EcN-cypate and facilitates the intratumoral infiltration of immune cells to realize desirable tumor eradication through photothermal therapy and ICD-induced immunotherapy. Our work provides a facile and noninvasive strategy to enhance the intratumoral delivery efficiency of natural/engineered bacteria, and may promote the clinical translation of bacteria-mediated synergistic cancer therapy.


Assuntos
Escherichia coli , Oxigenoterapia Hiperbárica , Imunoterapia , Terapia Fototérmica , Oxigenoterapia Hiperbárica/métodos , Animais , Imunoterapia/métodos , Camundongos , Terapia Fototérmica/métodos , Linhagem Celular Tumoral , Humanos , Morte Celular Imunogênica/efeitos dos fármacos , Neoplasias/terapia , Neoplasias/imunologia , Feminino , Camundongos Endogâmicos BALB C , Matriz Extracelular/metabolismo
14.
Adv Mater ; 36(18): e2311429, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38298173

RESUMO

Relieving inflammation via scavenging toxic reactive oxygen species (ROS) during the acute phase of spinal cord injury (SCI) proves to be an effective strategy to mitigate secondary spinal cord injury and improve recovery of motor function. However, commonly used corticosteroid anti-inflammatory drugs show adverse side effects which may induce increased risk of wound infection. Fortunately, hydrogen (H2), featuring selective antioxidant performance, easy penetrability, and excellent biosafety, is being extensively investigated as a potential anti-inflammatory therapeutic gas for the treatment of SCI. In this work, by a facile in situ growth approach of gold nanoparticles (AuNPs) on the piezoelectric BaTiO3, a particulate nanocomposite with Schottky heterojunction (Au@BT) is synthesized, which can generate H2 continuously by catalyzing H+ reduction through piezoelectric catalysis. Further, theoretical calculations are employed to reveal the piezoelectric catalytic mechanism of Au@BT. Transcriptomics analysis and nontargeted large-scale metabolomic analysis reveal the deeper mechanism of the neuroprotective effect of H2 therapy. The as-prepared Au@BT nanoparticle is first explored as a flexible hydrogen gas generator for efficient SCI therapy. This study highlights a promising prospect of nanocatalytic medicine for disease treatments by catalyzing H2 generation; thus, offering a significant alternative to conventional approaches against refractory spinal cord injury.


Assuntos
Ouro , Hidrogênio , Nanopartículas Metálicas , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/metabolismo , Hidrogênio/química , Catálise , Animais , Ouro/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Titânio/química , Camundongos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Nanocompostos/química
15.
Exploration (Beijing) ; 4(2): 20230105, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38855612

RESUMO

The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an "all-in-one" red blood cell (RBC)-derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are "immolated" under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

16.
J Control Release ; 357: 222-234, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36958404

RESUMO

Although nanocarriers have been widely applied in the delivery of anticancer drugs, many commercialized anticancer nanodrug systems still suffer from the problem of being easily trapped by lysosomes, which severely limits the drug delivery efficiency of a nanodrug system. Meanwhile, in drug-resistant tumors, the efflux of anticancer therapeutic drugs via the drug efflux transporters on the plasma membrane of cancer cells can significantly decrease the intracellular drug concentration and lead to the failure of the drug treatment. Here, we developed a small-molecule tyrosine kinase inhibitor (TKI)- and doxorubicin (Dox, a common anticancer drug)-loaded membrane fusion liposome (MFL) (termed Dox@Lapa-MFL) to achieve tumor cell membrane fusion-mediated drug delivery and enhanced chemotherapy of drug-resistant tumor. MFL could deliver drugs in a membrane fusion manner, circumventing the capture by lysosomes. Lapatinib, as the TKI doped in the MFL, could inhibit the efflux of Dox by ATP-binding cassette transporters (ABC transporters), further promoting the intracellular Dox accumulation. As a result, Dox achieved effective killing of drug-resistant tumors under the dual effect of MFL and lapatinib. To the best of our knowledge, it is the first example that employs membrane fusion-mediated TKI delivery for achieving tumor chemosensitization with good biosafety. This work presents an efficient and easily achievable strategy for treating drug-resistant tumors, which may hold promise for clinical applications.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Fusão de Membrana , Lapatinib/farmacologia , Resistencia a Medicamentos Antineoplásicos , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Lipossomos , Inibidores de Proteínas Quinases/farmacologia , Linhagem Celular Tumoral
17.
J Mater Chem B ; 10(16): 3073-3082, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35333270

RESUMO

Preservation of the intact cell morphology of bacteria is recognized as one important cause of bacterial drug resistance, and hence developing new antibacterial agents capable of fighting against bacteria via disrupting their cell envelope is highly desirable. Herein, by adopting a modified Stöber method, we developed a one-step approach to fabricate quaternized silica nanoparticles (NPs) using two commercially available molecules-a long alkyl chain-bearing quaternary ammonium silane compound, dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (Si-QAC), and tetraethyl orthosilicate (TEOS). Specifically, small spherical quaternized silica NPs with an average size of ∼34 nm could be prepared at a TEOS/Si-QAC molar ratio of 4 : 1 with a very high yield (>90%), and the resultant NPs (termed TS4 NPs) possessed superb colloidal stability (at least 520 d) and good biocompatibility. In addition, we confirmed that the long alkyl chain (C18)-bearing quaternary ammonium group endowed the TS4 NPs with the capacity to efficiently kill negatively charged Gram-positive bacteria via both hydrophobic and electrostatic interactions. Specifically, the TS4 NPs could coat the Staphylococcus aureus (S. aureus) cells via densely binding to the bacterial surface and induce the formation of TS4-S. aureus aggregates to exert their membrane disruption and reactive oxygen species (ROS) production effects, leading to the breakage of intracellular DNA and bacterial death. Besides, we revealed that TS4 could eradicate the mature S. aureus biofilms and inhibit the formation of S. aureus biofilms. The present work proposes a simple one-step method to prepare quaternized silica NPs with excellent bacterial adhesion and aggregation properties, which will find practical applications to fight against infections caused by bacteria and their biofilms.


Assuntos
Compostos de Amônio , Nanopartículas , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias , Aderência Bacteriana , Biofilmes , Dióxido de Silício/farmacologia , Staphylococcus aureus
18.
Biosens Bioelectron ; 213: 114403, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35696870

RESUMO

Visualizing the plasma membrane of living mammalian cells both in vitro and in vivo is crucial for tracking their cellular activities. However, due to the complex and dynamic nature of the plasma membrane, most commercial dyes for membrane staining can only realize very limited imaging performance. Thus, precise and stable plasma membrane imaging remains technically challenging. Here, by taking advantage of the small, well-defined, and amine-rich dendrimers, we prepared poly(ethylene glycol)-cholesterol (PEG-Chol)-conjugated and cyanine dye (e.g., cyanine2, cyanine3, and cyanine5)-labeled dendrimer nanoprobes (termed DPC-Cy2, DPC-Cy3, and DPC-Cy5 NPs). It was revealed that these probes enabled universal, wash-free, long-term (at least 8 h), and multicolor (green, yellow, and red) plasma membrane labeling of a variety of live mammalian cells. Further, we confirmed that the nanoprobes (using DPC-Cy5 as a representative) could achieve high-quality, wash-free, and stable cell surface labeling of live zebrafish embryos. More importantly, we demonstrated that our probes could act as biosensors to visualize the toxicity of metal-organic frameworks (MOFs) toward the epidermal cells of zebrafish embryos, and thus they hold great potential for identifying the toxic effect of drugs/materials at the single-cell scale or in live animals. The present work highlights the advantages of utilizing dendrimers for constructing functional imaging materials, and it is also believed that the fluorescent dendrimer nanoprobes developed in this work may find wide applications like cell imaging, drug toxicity evaluation, and cellular state monitoring.


Assuntos
Técnicas Biossensoriais , Dendrímeros , Animais , Membrana Celular/metabolismo , Dendrímeros/toxicidade , Corantes Fluorescentes/metabolismo , Corantes Fluorescentes/toxicidade , Mamíferos/metabolismo , Peixe-Zebra/metabolismo
19.
Exploration (Beijing) ; 2(5): 20220010, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37325504

RESUMO

Chemically manipulating bacterial surface structures, a cutting-edge research direction in the biomedical field, predominantly relies on metabolic labeling by now. However, this method may involve daunting precursor synthesis and only labels nascent surface structures. Here, we report a facile and rapid modification strategy based on a tyrosinase-catalyzed oxidative coupling reaction (TyOCR) for bacterial surface engineering. This strategy employs phenol-tagged small molecules and tyrosinase to initiate direct chemical modification of Gram-positive bacterial cell walls with high labeling efficiency, while Gram-negative bacteria are inert to this modification due to the hindrance of an outer membrane. By using the biotin‒avidin system, we further present the selective deposition of various materials, including photosensitizer, magnetic nanoparticle, and horseradish peroxidase, on Gram-positive bacterial surfaces, and realize the purification/isolation/enrichment and naked-eye detection of bacterial strains. This work demonstrates that TyOCR is a promising strategy for engineering live bacterial cells.

20.
Adv Sci (Weinh) ; 9(33): e2202933, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36202760

RESUMO

Acute kidney injury (AKI) is a sudden kidney dysfunction caused by aberrant reactive oxygen species (ROS) metabolism that results in high clinical mortality. The rapid development of ROS scavengers provides new opportunities for AKI treatment. Herein, the use of hydrogen-terminated germanene (H-germanene) nanosheets is reported as an antioxidative defense nanoplatform against AKI in mice. The simulation results show that 2D H-germanene can effectively scavenge ROS through free radical adsorption and subsequent redox reactions. In particular, the H-germanene exhibits high accumulation in injured kidneys, thereby offering a favorable opportunity for treating renal diseases. In the glycerol-induced murine AKI model, H-germanene delivers robust antioxidative protection against ROS attack to maintain normal kidney function indicators without negative influence in vivo. This positive in vivo antioxidative defense in living animals demonstrates that the present H-germanene nanoplatform is a powerful antioxidant against AKI and various anti-inflammatory diseases.


Assuntos
Injúria Renal Aguda , Antioxidantes , Camundongos , Animais , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Injúria Renal Aguda/tratamento farmacológico , Rim/metabolismo , Anti-Inflamatórios
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