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1.
Int J Mol Sci ; 23(18)2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36142339

RESUMO

Plants must balance both beneficial (symbiotic) and pathogenic challenges from microorganisms, the former benefitting the plant and agriculture and the latter causing disease and economic harm. Plant innate immunity describes a highly conserved set of defense mechanisms that play pivotal roles in sensing immunogenic signals associated with both symbiotic and pathogenic microbes and subsequent downstream activation of signaling effector networks that protect the plant. An intriguing question is how the innate immune system distinguishes "friends" from "foes". Here, we summarize recent advances in our understanding of the role and spectrum of innate immunity in recognizing and responding to different microbes. In addition, we also review some of the strategies used by microbes to manipulate plant signaling pathways and thus evade immunity, with emphasis on the use of effector proteins and micro-RNAs (miRNAs). Furthermore, we discuss potential questions that need addressing to advance the field of plant-microbe interactions.


Assuntos
MicroRNAs , Imunidade Vegetal , Imunidade Inata , MicroRNAs/genética , Doenças das Plantas , Plantas/genética , Simbiose
2.
Environ Res ; 200: 111474, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34097891

RESUMO

Hybrid composites based on transition metal-doped materials exhibit excellent performance and stability as electrocatalysts for the hydrogen evolution reaction (HER). Thus, they could easily replace HER catalysts based on noble metals. To demonstrate this, we fabricated Co, Fe, and CoS doped N-enriched porous carbon materials (CoFeS/NC) using a simple, straightforward and quick method (involving absorption, pyrolysis and sulfidation steps), which used ZIF-67 metal-organic framework (MOF) material as a precursor. The fabricated CoFeS/NC showed excellent HER performance and long-term stability: it achieved a low potential (equal to 176 mV) at 10 mA cm-2 current density and a small Tafel slope (equal to 67.8 mV dec-1) in 1.0 KOH. Such outstanding HER performance was attributed to the synergistic effect of the CoFeS/NC components, including unique mesoporosity. All these properties ensured the presence of numerous active sites and high conductivity provided by the carbon matrix. The excellent CoFeS/NC electrocatalytic activity makes it a promising material for H2 production on an industrial scale. Our work demonstrated a simple way of its preparation, which could be applied to other material groups.


Assuntos
Carbono , Hidrogênio , Catálise , Porosidade , Pirólise
3.
J Nanobiotechnology ; 17(1): 8, 2019 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-30660200

RESUMO

BACKGROUND: Leading to more and more deaths and disabilities, stroke has become a serious threat to human health. What's more, few effective drugs are available in clinic till now. RESULTS: In this research, we prepared a novel neuroprotective nanoformation (OEA-SPC NPs) via the combination of the nanoparticle drug delivery system with the endogenous N-oleoylethanolamine (OEA). By forming hydrogen bond between OEA and the carrier-soybean phosphatidylcholine (SPC), the form of OEA was turned into amorphus state when loading to the nanoparticles, which greatly improved its bioavailability. Then the following systematic experiments revealed the efficient neuroprotective effect of OEA-SPC NPs in vivo. Compared with the MCAO group, the cerebral infarct volume was reduced by 81.1%, and the edema degree by 78.4% via the oral administration of OEA-SPC NPs. And the neurological deficit scores illustrated that the MCAO rats treated with OEA-SPC NPs exhibited significantly less neurological dysfunction. The Morris water maze test indicated that the spatial learning and memory of cerebral ischemia model rats were almost recovered to the normal level. Besides, the OEA-SPC NPs could inhibit the inflammation of reperfusion to a very slight level. CONCLUSIONS: These results suggest that the OEA-SPC NPs have a great chance to be a potential anti-stroke formation for clinic application and actually bring hope to thousands of stroke patients.


Assuntos
Agonistas de Receptores de Canabinoides/farmacologia , Endocanabinoides/farmacologia , Etanolaminas/farmacologia , Nanopartículas , Ácidos Oleicos/farmacologia , Fosfatidilcolinas , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Sprague-Dawley
4.
J Nanobiotechnology ; 16(1): 90, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30424776

RESUMO

BACKGROUND: In the last decade, the biosynthesis of metal nanoparticles using organisms have received more and more considerations. However, the complex composition of organisms adds up to a great barrier for the characterization of biomolecules involved in the synthesis process and their biological mechanisms. RESULTS: In this research, we biosynthesized a kind of flower-shaped Au nanoclusters (Au NCs) using one definite component-epigallocatechin gallate (EGCG), which was the main biomolecules of green tea polyphenols. Possessing good stability for 6 weeks and a size of 50 nm, the Au NCs might be a successful candidate for drug delivery. Hence, both methotrexate (MTX) and doxorubicin (DOX) were conjugated to the Au NCs through a bridge of cysteine (Cys). The introduction of MTX provided good targeting property for the Au NCs, and the conjugation of DOX provided good synergistic effect. Then, a novel kind of dual-drug loaded, tumor-targeted and highly efficient drug delivery system (Au-Cys-MTX/DOX NCs) for combination therapy was successfully prepared. The TEM of HeLa cells incubated with Au-Cys-MTX/DOX NCs indicated that the Au-Cys-MTX/DOX NCs could indeed enter and kill cancer cells. The Au-Cys-MTX/DOX NCs also possessed good targeting effect to the FA-receptors-overpressed cancer cells both in vitro and in vivo. Importantly, the Au-Cys-MTX/DOX NCs resulted in an excellent anticancer activity in vivo with negligible side effects. CONCLUSIONS: These results suggest that the biosynthesized Au-Cys-MTX/DOX NCs could be a potential carrier with highly efficient anticancer properties for tumor-targeted drug delivery.


Assuntos
Antineoplásicos/química , Catequina/análogos & derivados , Portadores de Fármacos/química , Ouro/química , Nanopartículas Metálicas/química , Animais , Antineoplásicos/farmacologia , Catequina/química , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Doxorrubicina/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Células HeLa , Células Hep G2 , Humanos , Metotrexato/química , Metotrexato/farmacologia , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Propriedades de Superfície
5.
J Nanobiotechnology ; 15(1): 91, 2017 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-29258613

RESUMO

BACKGROUND: Since the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors. RESULTS: In this study, we developed a kind of dual drug [methotrexate (MTX) and 10-hydroxycamptothecine (HCPT)] loaded nanoneedles (DDNDs) with pronounced targeting property, high drug loading and prolonged drug release. The anti-solvent precipitation of the HCPT and MTX modified PEG-b-PLGA (PEG-b-PLGA-MTX, PPMTX) leads to nucleation of nanoneedles with nanocrystalline HCPT as the core wrapped with PPMTX as steric stabilizers. In vitro cell uptake studies showed that the DDNDs revealed an obviously targeting property and entered the HeLa cells easier than the nanoneedles without MTX modification. The cytotoxicity tests illustrated that the DDNDs possessed better killing ability to HeLa cells than the individual drugs or their mixture in the same dose, indicating its good synergistic effect and targeting property. The in vivo studies further confirmed these conclusions. CONCLUSIONS: This approach led to a promising sustained drug delivery system for cancer diagnosis and treatment.


Assuntos
Antineoplásicos/química , Camptotecina/análogos & derivados , Portadores de Fármacos/química , Metotrexato/química , Nanopartículas/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/metabolismo , Camptotecina/administração & dosagem , Camptotecina/química , Camptotecina/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Células HeLa , Humanos , Metotrexato/administração & dosagem , Metotrexato/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Microscopia Confocal , Microscopia Eletrônica de Varredura , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Polietilenoglicóis/química , Poliglactina 910/química , Distribuição Tecidual , Transplante Heterólogo
6.
Yao Xue Xue Bao ; 51(8): 1309-15, 2016 08.
Artigo em Zh | MEDLINE | ID: mdl-29906035

RESUMO

In this study, we used Shirasu porous glass membrane(SPG) as a template and hydroxy camptothecin (HCPT) as a model drug to prepare the comet-shaped Me PEG [methoxyl poly(ethylene glycol)]- PLGA [poly(lactic-co-glycolic acid)-HCPT amphiphilic block copolymer. Our method was optimized by the orthogonal design method. The partical size, zeta potential, drug-loaded content, yield, shape and status of the obtained comet-shaped Me PEG-PLGA-HCPT particles were further characterized by dynamic light scattering(DLS), scanning electron microscopy(SEM)/transmission electron microscopy (TEM), X-ray diffraction(XRD) and differential scanning calorimetry (DSC) et al, respectively. In vitro release was preliminary evaluated. MTT assay to preliminary evaluate the cytotoxicity of particles against human liver BEL-7402 cells. Based on these experimental results, the optimal preparation conditions contain: weight ratio of HCPT to Me PEG-PLGA was 1:1, nitrogen pressure was 100 k Pa and SPG membrane pore size was 1.1 µm. The particles exhibited a comet-shaped shape, fairly uniform size and were well dispersed. The drug-loading content was 46.2%, with yield of 96.4%, and zeta-31.4 m V. The distribution of HCPT in particles was very uniform, and HCPT showed a amorphous state existed in particles. The release behavior in vitro showed sustained releasing, and with the drug loading content in proportion to the release of the drug. MTT test indicated that the HCPT-loaded comet-shaped particles had enhanced the cytotoxicity against human liver BEL-7402 cells relatively to the HCPT-loaded spherical particles in vitro. The results showed a promising potential application of the preparation in clinical treatment of tumor.


Assuntos
Camptotecina/administração & dosagem , Portadores de Fármacos/química , Ácido Láctico/química , Ácido Poliglicólico/química , Varredura Diferencial de Calorimetria , Linhagem Celular , Humanos , Nanopartículas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Difração de Raios X
7.
Mol Pharm ; 12(4): 1318-27, 2015 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-25710590

RESUMO

The particle shape of the drug delivery systems had a strong impact on their in vitro and in vivo performance, but there was limited availability of techniques to produce the specific shaped drug carriers. In this article, the novel methotrexate (MTX) decorated MPEG-PLA nanobacillus (MPEG-PLA-MTX NB) was prepared by the self-assembly technique followed by the extrusion through SPG membrane with high N2 pressure for targeted drug delivery, in which Janus-like MTX was not only used as a specific anticancer drug but could also be served as a tumor-targeting ligand. The MPEG-PLA-MTX NBs demonstrated much higher in vitro and in vivo targeting efficiency compared to the MPEG-PLA-MTX nanospheres (MPEG-PLA-MTX NSs) and MPEG-PLA nanospheres (MPEG-PLA NSs). In addition, the MPEG-PLA-MTX NBs also displayed much more excellent in vitro and in vivo antitumor activity than the MPEG-PLA-MTX NSs and free MTX injection. To our knowledge, this work provided the first example of the integration of the shape design (which mediated an early phase tumor accumulation and a late-phase cell internalization) and Janus-faced function (which mediated an early phase active targeting effect and a late-phase anticancer effect) on the basis of nanoscaled drug delivery systems. The highly convergent and cooperative drug delivery strategy opens the door to more drug delivery systems with new shapes and functions for cancer therapy.


Assuntos
Bacillus , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Polímeros/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Portadores de Fármacos/química , Citometria de Fluxo , Células HeLa , Humanos , Ácido Láctico/química , Metotrexato/administração & dosagem , Camundongos , Nanopartículas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química
8.
Mol Pharm ; 11(8): 2915-27, 2014 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-24984984

RESUMO

Most present drug-phospholipid delivery systems were based on a water-insoluble drug-phospholipid complex but rarely water-soluble drug-phospholipid complex. Mitomycin C (MMC) is a water-soluble anticancer drug extensively used in first-line chemotherapy but is limited by its poor aqueous stability in vitro, rapid elimination from the body, and lack of target specificity. In this article, we report the MMC-soybean phosphatidylcholine complex-loaded PEG-lipid-PLA hybrid nanoparticles (NPs) with Folate (FA) functionalization (FA-PEG-PE-PLA NPs@MMC-SPC) for targeted drug delivery and dual-controlled drug release. FA-PEG-PE-PLA NPs@MMC-SPC comprise a hydrophobic core (PLA) loaded with MMC-SPC, an amphiphilic lipid interface layer (PE), a hydrophilic shell (PEG), and a targeting ligand (FA) on the surface, with a spherical shape, a nanoscaled particle size, and high drug encapsulation efficiency of almost 95%. The advantage of the new drug delivery systems is the early phase controlled drug release by the drug-phospholipid complex and the late-phase controlled drug release by the pH-sensitive polymer-lipid hybrid NPs. In vitro cytotoxicity and hemolysis assays demonstrated that the drug carriers were cytocompatible and hemocompatible. The pharmacokinetics study in rats showed that FA-PEG-PE-PLA NPs@MMC-SPC significantly prolonged the blood circulation time compared to that of the free MMC. More importantly, FA-PEG-PE-PLA NPs@MMC-SPC presented the enhanced cell uptake/cytotoxicity in vitro and superior tumor accumulation/therapeutic efficacy in vivo while reducing the systemic toxicity. A significant accumulation of MMC in the nuclei as the site of MMC action achieved in FA-PEG-PE-PLA NPs@MMC-SPC made them ideal for MMC drug delivery. This study may provide an effective strategy for the design and development of the water-soluble drug-phospholipid complex-based targeted drug delivery and sustained/controlled drug release.


Assuntos
Sistemas de Liberação de Medicamentos , Glycine max/química , Mitomicina/química , Nanopartículas/química , Fosfatidilcolinas/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular , Células HeLa , Hemólise/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico/química , Ligantes , Masculino , Camundongos , Transplante de Neoplasias , Tamanho da Partícula , Poliésteres , Polietilenoglicóis/química , Polímeros/química , Ratos , Ratos Sprague-Dawley , Solubilidade , Água/química
9.
Mol Pharm ; 11(9): 3017-26, 2014 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-25054963

RESUMO

A mitomycin C (MMC)-soybean phosphatidyhlcholine complex loaded in phytosomes was previously reported for the purpose of developing a MMC drug delivery system (Mol. Pharmaceutics 2013, 10, 90-101), but this approach was limited by rapid elimination from the body and lack of target specificity. In this article, to overcome these limitations, MMC-soybean phosphatidyhlcholine complex-loaded phytosomes (MMC-loaded phytosomes) as drug carriers were surface-functionalized with folate-PEG (FA-PEG) to achieve reduced toxicity and a superior MMC-mediated therapeutic effect. For this purpose, FA was conjugated to DSPE-PEG-NH2, and the resultant DSPE-PEG-FA was introduced into the lipid moiety of the phytosomes via a postinsertion technique. The prepared FA-PEG-functionalized MMC-loaded phytosomes (FA-PEG-MMC-loaded phytosomes) have a particle size of 201.9 ± 2.4 nm, a PDI of 0.143 ± 0.010, a zeta potential of -27.50 ± 1.67 mV, a spherical shape, and sustained drug release. The remarkable features of FA-PEG-MMC-loaded phytosomes included increased cellular uptake in HeLa cells and higher accumulation in H22 tumor-bearing mice over that of the PEG-MMC-loaded phytosomes. Furthermore, FA-PEG-MMC-loaded phytosomes were associated with enhanced cytotoxic activity in vitro and an improved antitumor effect in vivo compared to that resulting from free MMC injection. These results suggest that FA-PEG-MMC-loaded phytosomes may be useful drug delivery systems for widening the therapeutic window of MMC in clinical trials.


Assuntos
Ácido Fólico/análogos & derivados , Ácido Fólico/química , Glycine max/química , Lipossomos/química , Mitomicina/química , Polietilenoglicóis/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular Tumoral , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/administração & dosagem , Células HeLa , Humanos , Lipossomos/administração & dosagem , Masculino , Camundongos , Camundongos Nus , Mitomicina/administração & dosagem , Tamanho da Partícula , Fosfatidiletanolaminas/administração & dosagem , Fosfatidiletanolaminas/química , Polietilenoglicóis/administração & dosagem , Polímeros/administração & dosagem , Polímeros/química , Ratos , Ratos Sprague-Dawley
10.
Front Chem ; 10: 1014208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157031

RESUMO

With high mortality, stroke has become a serious threat to human health. Nevertheless, the strategy for stroke therapy is quite limited in the clinic till now. In this research, we prepared a novel neuroprotective nanoformulation (OEA Liposomes) via encapsulating endogenous N-oleoylethanolamine (OEA) in liposomes for intravenous administration. The formulation largely increased the solubility and bioavailability of OEA. Then the following systematic experiments stated the excellent neuroprotective effect of OEA Liposomes in vivo. The survival rate of the nanodrug group was largely increased to 75%, while that of the Middle Cerebral Artery Occlusion (MCAO) group was only 41.7%. And the severe neurological functional deficit of the MCAO rats was also significantly improved. What's more, the OEA Liposomes could inhibit the apoptosis of neurons and the inflammation of reperfusion to a very slight level, indicating their outstanding neuroprotective effect. These results indicated that the OEA Liposomes have a great potential for clinic anti-stroke application.

11.
Front Bioeng Biotechnol ; 10: 945148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35903793

RESUMO

The strategy for dual drug-loaded nanomedicine with targeting properties was always complex. Herein, a novel strategy for the preparation of metal-organic particle-based nanomedicine has been developed, and combretastatin A4 (CA4) and mitoxantrone (MIT) loaded MOPs (CMMOPs) have been obtained. In this system, using merely Cu(II) as a bridge to connect and coordinate with the dual drugs has resulted in the CMMOPs possessing a fairly high drug load of almost 90%. Moreover, the coordination between Cu(II) and the drugs was stable at physiological pH but easily cleavable in the tumor acidic microenvironment, which would provide a good targeting property for CMMOPs. The in vivo experiments indicated that CMMOPs possessed a significantly enhanced antitumor efficiency with negligible side effects. The results suggest that CMMOPs could be a potential anticancer formulation for tumor-targeted drug delivery.

12.
Drug Deliv ; 28(1): 2525-2533, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34842016

RESUMO

Causing more and more deaths, stroke has been a leading cause of death worldwide. However, success in clinical stroke trials has remained elusive. N-oleoylethanolamine (OEA) was an endogenous highly hydrophobic molecule with outstanding neuroprotective effect. In this article, hydrogen bonds were successfully formed between OEA and soybean phosphatidylcholine (SPC). The synthetic OEA-SPC complex and DSPE-PEG were self-assembled into liposomes (OEA NPs), with OEA-SPC loaded in the core and PEG formed a hydrophilic shell. Hence, highly hydrophobic OEA was loaded into liposomes as amorphous state with a drug loading of 8.21 ± 0.18 wt%. With fairly uniform size and well-distributed character, the OEA NPs were systemically assessed as an intravenous formulation for stroke therapy. The results indicated that the administration of OEA NPs could significantly improve the survival rate and the Garcia score of the MCAO rats compared with free OEA. The TTC-stained brain slices declared that the cerebral infarct volume and the edema degree induced by MCAO could be decreased to an extremely low level via the administration of OEA NPs. The Morris water maze (MWM) test suggested that the spatial learning and memory of the MCAO rats could also be ameliorated by OEA NPs. The immunofluorescence assay stated that the apoptosis of the neurons and the inflammation within the brain were greatly inhibited. The results suggest that the OEA NPs have a great chance to develop OEA as a potential anti-stroke formulation for clinic application.


Assuntos
Portadores de Fármacos/química , Endocanabinoides/administração & dosagem , Endocanabinoides/farmacologia , Etanolaminas/administração & dosagem , Etanolaminas/farmacologia , Lipossomos/química , Ácidos Oleicos/administração & dosagem , Ácidos Oleicos/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Química Farmacêutica , Modelos Animais de Doenças , Liberação Controlada de Fármacos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Ratos , Ratos Sprague-Dawley
13.
Int J Nanomedicine ; 16: 8103-8115, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34992362

RESUMO

INTRODUCTION: Although the preparation of lipid nanoparticles (LNPs) achieves great success, their retention of highly hydrophobic drugs is still problematic. METHODS: Herein, we report a novel strategy for efficiently loading hydrophobic drugs to LNPs for stroke therapy. Oleoylethanolamide (OEA), an endogenous highly hydrophobic molecule with outstanding neuroprotective effect, was successfully loaded to OEA-SPC&DSPE-PEG lipid nanoparticles (OSDP LNPs) with a drug loading of 15.9 ± 1.2 wt%. Efficient retention in OSDP LNPs greatly improved the pharmaceutical property and enhanced the neuroprotective effect of OEA. RESULTS: Through the data of positron emission tomography (PET) and TTC-stained brain slices, it could be clearly visualized that the acute ischemic brain tissues were preserved as penumbral tissues and bounced back with reperfusion. The in vivo experiments stated that OSDP LNPs could significantly improve the survival rate, the behavioral score, the cerebral infarct volume, the edema degree, the spatial learning and memory ability of the MCAO (middle cerebral artery occlusion) rats. DISCUSSION: These results suggest that the OSDP LNPs have a great chance to develop hydrophobic OEA into a potential anti-stroke formulation.


Assuntos
Nanopartículas , Acidente Vascular Cerebral , Animais , Endocanabinoides , Lipossomos , Ácidos Oleicos , Ratos , Acidente Vascular Cerebral/tratamento farmacológico
14.
Nanoscale Res Lett ; 12(1): 416, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28622716

RESUMO

Since the hydrophobic group is always essential to the synthesis of the drug-loaded nanoparticles, a majority of the methods rely heavily on organic solvent, which may not be completely removed and might be a potential threat to the patients. In this study, we completely "green" synthesized 10-hydroxycamptothecine (HCPT) loaded, folate (FA)-modified nanoneedles (HFNDs) for highly efficient cancer therapy with high drug loading, targeting property, and imaging capability. It should be noted that no organic solvent was used in the preparation process. In vitro cell uptake study and the in vivo distribution study showed that the HFNDs, with FA on the surface, revealed an obviously targeting property and entered the HeLa cells easier than the chitosan-HCPT nanoneedles without FA modified (NDs). The cytotoxicity tests illustrated that the HFNDs possessed better killing ability to HeLa cells than the individual drug or the NDs in the same dose, indicating its good anticancer effect. The in vivo anticancer experiment further revealed the pronounced anticancer effects and the lower side effects of the HFNDs. This new method without organic solvent will lead to a promising sustained drug delivery system for cancer diagnosis and treatment.

15.
Drug Deliv ; 24(1): 51-60, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28155539

RESUMO

Exploration of efficient dual-drug nanohybrids, particularly those with high drug loading, specific targeting property, and long-termed stability, is of highly importance in cancer therapy. A pH-driven coprecipitation was performed in the aqueous phase to obtain a dual-drug nanoformulation, composed of 10-hydroxycamptothecine (HCPT) nanoneedles integrated with an exterior thin layer of the methotrexate (MTX)-chitosan conjugate. The high stability of nanohybrids in water and the targeting property provided by the MTX ingredient function synergistically to the prolonged and sustained drug release property in tumor tissues and the increased cellular uptake. The cytotoxicity test illustrates that dual-drug nanoneedles possess the remarkable killing ability to HeLa cells with the combination index at 0.33 ± 0.07. After cellular internalization, the release of both drug ingredients results in an excellent anticancer activity in vivo with the minimized adverse side effects. Design of a green approach to the carrier-free, dual-drug nanoformulations enables to develop emerging drug delivery systems for cancer diagnosis and treatment.


Assuntos
Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/análogos & derivados , Quitosana/química , Portadores de Fármacos , Química Verde , Metotrexato/administração & dosagem , Nanopartículas , Tecnologia Farmacêutica/métodos , Neoplasias do Colo do Útero/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Disponibilidade Biológica , Camptotecina/administração & dosagem , Camptotecina/química , Camptotecina/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Combinação de Medicamentos , Composição de Medicamentos , Estabilidade de Medicamentos , Sinergismo Farmacológico , Feminino , Células HeLa , Humanos , Metotrexato/química , Metotrexato/farmacocinética , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanomedicina , Solubilidade , Distribuição Tecidual , Carga Tumoral/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Nanoscale Res Lett ; 11(1): 294, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27299649

RESUMO

The high-aspect-ratio nanoparticles were proved to be internalized much more rapidly and efficiently by cancer cells than the nanoparticles with an equal aspect ratio. Herein, a kind of high-aspect ratio, pointed-end nanoneedles (NDs) with a high drug loading (15.04 %) and the prolonged drug release profile were fabricated with an anti-tumor drug-10-hydroxycamptothecin (HCPT)-via an ultrasound-assisted emulsion crystallization technique. It is surprising to see that the cellular internalization of NDs with an average length of 5 µm and an aspect ratio of about 12:1 was even much faster and higher than that of nanorods with the same size and the nanospheres with a much smaller size of 150 nm. The results further validated that cellular internalization of the nanoparticles exhibited a strong shape-dependent effect, and cellular uptake may favor the particles with sharp ends as well as a high-aspect ratio instead of particle size. The NDs with enhanced cytotoxicity would lead to a promising sustained local drug delivery system for highly efficient anticancer therapy. More importantly, the fabrication of NDs opens a door to design new formulations of nanoneedle drug delivery systems for highly efficient cancer.

17.
ACS Appl Mater Interfaces ; 7(46): 25553-9, 2015 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-26529185

RESUMO

We constructed 10-hydroxycamptothecin (CPT) "nanodrugs" with functionalization of lipid-PEG-methotrexate (MTX) to prepare high-drug-loaded, and sustained/controlled-release MTX-PEG-CPT nanorods (NRs), in which MTX drug itself can serve as a specific "targeting ligand". The self-targeted nanodrug can codeliver both CPT and MTX drugs with distinct anticancer mechanisms. Furthermore, MTX-PEG-CPT NRs significantly reduced burst release, improved blood circulation and tumor accumulation, enhanced cellular uptake, and synergistically increased anticancer effect against tumor cells compared with MTX-PEG-CPT nanospheres (NSs) and either both free drugs or individual free drug. Therefore, the synergistic targeting/therapeuticy nano-multi-drug codelivery assisted by shape design may advantageously offer a promising new strategy for nanomedicine.


Assuntos
Antineoplásicos/farmacologia , Camptotecina/análogos & derivados , Núcleo Celular/metabolismo , Metotrexato/farmacologia , Nanotubos/química , Animais , Camptotecina/farmacologia , Linhagem Celular Tumoral , Núcleo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Sinergismo Farmacológico , Endocitose/efeitos dos fármacos , Fluorescência , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanosferas/química , Nanosferas/ultraestrutura , Nanotubos/ultraestrutura , Tamanho da Partícula , Ratos Sprague-Dawley
18.
Chem Sci ; 6(3): 1650-1654, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28694944

RESUMO

Delicate mesoscopic architectures, bearing complex forms with multiple hierarchy levels, lead to significant functions in biogenic minerals. Herein, a bio-inspired approach was developed to fabricate comet-shaped assemblies of an anti-tumor drug - 10-hydroxycamptothecin (HCPT). The anti-solvent co-precipitation of HCPT and the excipient - PEG-b-PLGA - within the emulsifier leads to the immediate nucleation of comet bundles, followed by a secondary nucleation to generate the comet head, which is an assembly of nanofibers aligned almost in parallel. The continuous manufacturing furnishes drug-excipient hybrid particles with high drug-loading and a sustained drug release profile. This simple and efficient bio-inspired approach led to a promising sustained local drug delivery system, and could be extended to the fabrication of other functional organic materials bearing mesoscopic structural units.

19.
ACS Appl Mater Interfaces ; 7(32): 17573-81, 2015 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-26234408

RESUMO

Integrating advantages of mitomycin C (MMC)-phospholipid complex for increased drug encapsulation efficiency and reduced premature drug release, DSPE-PEG-folate (DSPE-PEG-FA) for specific tumor targeting, we reported a simple one-pot self-assembly route to prepare the MMC-phospholipid complex-loaded DSPE-PEG-based nanoparticles (MP-PEG-FA NPs). Both confocal imaging and flow cytometry demonstrated that MMC was distributed into nuclei after cellular uptake and intracellular drug delivery. More importantly, the systemically administered MP-PEG-FA NPs led to increased blood persistence and enhanced tumor accumulation in HeLa tumor-bearing nude mice. This study introduces a simple and effective strategy to design the anticancer drug-phospholipid complex-based targeted drug delivery system for sustained/controlled drug release.


Assuntos
Antineoplásicos/química , Portadores de Fármacos/química , Nanopartículas/química , Fosfolipídeos/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/metabolismo , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Feminino , Ácido Fólico/análogos & derivados , Ácido Fólico/química , Meia-Vida , Células HeLa , Humanos , Camundongos , Camundongos Nus , Microscopia Confocal , Mitomicina/administração & dosagem , Mitomicina/química , Mitomicina/farmacocinética , Polietilenoglicóis/química , Ratos , Distribuição Tecidual , Transplante Heterólogo , Neoplasias do Colo do Útero/tratamento farmacológico
20.
Nanoscale Res Lett ; 9(1): 2408, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26088984

RESUMO

We present a dialysis technique to prepare the 10-hydroxycamptothecin (HCPT)-loaded nanoparticles (NPs) using methoxypolyethylene glycol-poly(D,L-lactide) (PEG-b-PLA) and PLA, respectively. Both HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs were characterized by differential scanning calorimetry (DSC), dynamic light scattering (DLS), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). The results showed that the HCPT-loaded PEG-b-PLA NPs and HCPT-loaded PLA NPs presented a hydrodynamic particle size of 120.1 and 226.8 nm, with a polydispersity index of 0.057 and 0.207, a zeta potential of -31.2 and -45.7 mV, drug encapsulation efficiency of 44.52% and 44.94%, and drug-loaded content of 7.42% and 7.49%, respectively. The HCPT-loaded PEG-b-PLA NPs presented faster drug release rate compared to the HCPT-loaded PLA NPs. The HCPT-loaded PEG-b-PLA NPs presented higher cytotoxicity than the HCPT-loaded PLA NPs. These results suggested that the HCPT-loaded PEG-b-PLA NPs presented better characteristics for drug delivery compared to HCPT-loaded PLA NPs.

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