Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Nat Biotechnol ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336902

RESUMO

The efficacy of oncolytic adenoviruses (OAs) for cancer therapy has been limited by insufficient delivery to tumors after systemic injection and the propensity of OAs to induce the expression of immune checkpoints. To address these limitations, we use T cells to deliver OAs into tumors and engineer the OA to express a Cas9 system targeting the PDL1 gene encoding the immune checkpoint protein PD-L1. By cloaking OAs with cell membranes presenting T cell-specific antigens, we physically conjugated OAs onto T cell surfaces by antigen-receptor interaction. We tested the oncolytic virus-T cell chimera (ONCOTECH) via intravenous delivery in mouse cancer models, including models of melanoma, pancreatic adenocarcinoma, lung cancer and glioblastoma. In the melanoma model, the in vivo delivery of ONCOTECH resulted in a strong accumulation of OAs in tumor cells, where PD-L1 expression was reduced by 50% and the single administration of ONCOTECH enabled 80% survival over 70 days. Collectively, ONCOTECH represents a promising translational technology to combine virotherapy and cell therapy.

2.
Small ; 20(1): e2304491, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37653587

RESUMO

A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu2+ -to-Cu+ photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu+ . Bb mediates photogeneration of hydroxyl radicals (•OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of •OH based on Bb and the Cu+ species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model.


Assuntos
Fibroblastos Associados a Câncer , Estruturas Metalorgânicas , Neoplasias , Humanos , Estruturas Metalorgânicas/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Microambiente Tumoral , Cobre/metabolismo , Neoplasias/metabolismo , Linhagem Celular Tumoral
3.
Adv Mater ; 35(48): e2302503, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37681753

RESUMO

Only a minority of rheumatoid arthritis (RA) patients achieve disease remission, so the exploration of additional pathogenic factors and the development of new therapeutics are needed. Here, strong correlations among the cell-free DNA (cfDNA) level and the inflammatory response in clinical synovial fluid samples and RA disease activity are discovered. The important role of cfDNA in disease development in a collagen-induced arthritis (CIA) murine model is also demonstrated. Building on these findings, a novel therapeutic based on anti-inflammatory (M2) macrophage-derived exosomes as chassis, that are modified with both oligolysine and matrix metalloproteinase (MMP)-cleavable polyethylene glycol (PEG) on the membrane, is developed. After intravenous injection, PEG-enabled prolonged circulation and C─C motif chemokine ligand-directed accumulation together result in enrichment at inflamed joints. Following subsequent MMP cleavage, the positively charged oligolysine is exposed for cfDNA scavenging, while exosomes induce M2 polarization. By using a classical CIA murine model and a newly established CIA canine model, it is demonstrated that the rationally designed exosome therapeutic substantially suppresses inflammation in joints and provides strong chondroprotection and osteoprotection, revealing its potential for effective CIA amelioration.


Assuntos
Artrite Experimental , Artrite Reumatoide , Exossomos , Humanos , Animais , Cães , Camundongos , Modelos Animais de Doenças , Exossomos/patologia , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/patologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/induzido quimicamente , Artrite Experimental/patologia , Macrófagos/patologia
4.
Nat Commun ; 14(1): 4505, 2023 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-37495590

RESUMO

The therapeutic efficacy of whole tumor cell vaccines (TCVs) is modest, which has delayed their translation into personalized immunotherapies in the clinic. Here, we develop a TCV platform based on photothermal nanoparticle-loaded tumor cells, which can be rationally applied to diverse tumor types to achieve on-demand boost of anti-tumor immune responses for inhibiting tumor growth. During the fabrication process, mild photothermal heating by near-infrared (NIR) laser irradiation induces the nanoparticle-bearing tumor cells to express heat shock proteins as endogenous adjuvants. After a single vaccination at the back of tumor-bearing mice, non-invasive NIR laser irradiation further induces mild hyperthermia at vaccination site, which promotes the recruitment, activation, and antigen presentation by dendritic cells. Using an indicator we term fluctuation of tumor growth rate, we determine appropriate irradiation regimens (including optimized irradiation intervals and times). This TCV platform enables on-demand NIR manipulation of immune responses, and we demonstrate potent therapeutic efficacy against six murine models that mimick a range of clinical scenarios, including a model based on humanized mice and patient-derived tumor xenografts.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Vacinas , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Fototerapia , Neoplasias/terapia , Apresentação de Antígeno , Modelos Animais de Doenças , Lasers
5.
Chemphyschem ; 24(6): e202200716, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36404675

RESUMO

Room temperature phosphorescence (RTP) materials are characterized with emission after removing the excitation source. Such long-lived emission feature possesses great potential in biological fluorescence imaging because it enables a way regarding temporal dimension for separating the interference of autofluorescence and common noises typically encountered in conventional fluorescence imaging. Herein, we constructed a new type of mesoporous silica nanoparticles (MSNs)-based composite nanoparticles (NPs) with dual-color long-lived emission, namely millisecond-level green phosphorescence and sub-millisecond-level delayed red fluorescence by encapsulating a typical RTP dye and Rhodamine dye in the cavities of the MSNs with the former acting as energy donor (D) while the latter as acceptor (A). Benefiting from the close D-A proximity, energy match between the donor and the acceptor and the optimized D/A ratio in the composite NPs, efficient triplet-to-singlet Förster resonance energy transfer (TS-FRET) in the NPs occurred upon exciting the donor, which enabled dual-color long-lived emission. The preliminary results of dual-color correlation imaging of live cells based on such emission feature unequivocally verified the unique ability of such NPs for distinguishing the false positive generated by common emitters with single-color emission feature.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Nanopartículas , Transferência Ressonante de Energia de Fluorescência/métodos , Rodaminas , Nanopartículas/química
6.
Biomater Sci ; 10(19): 5520-5534, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-35924482

RESUMO

A new type of polymeric nanomicelle-based nanoagent (denoted as PT@MFH hereafter) capable of the highly sensitive release of the chemotherapeutic drug paclitaxel (PTX) upon exposure to a near-infrared (NIR) laser trigger was developed. Specifically, PTX and a photothermal polymer (T-DPPT) were encapsulated in the cavity of nanomicelles, which were constructed from an amphiphilic block copolymer (PCL-PEEP) with a lower critical solution temperature (LCST) of ∼54 °C. Owing to the unprecedented ability of the T-DPPT moiety to harvest near-infrared light, with a mass extinction coefficient at 808 nm of up to ∼80.8 L g-1 cm-1, and convert NIR light to heat, with a photothermal conversion efficiency (η) of up to ∼70%, local hyperthermia was promptly realized via irradiation from an 808 nm laser with extraordinarily low output power. This enabled remarkable contrast in the local temperature and drug release between the "silent" state (prior to phototriggering) and the "activated" state (after phototriggering). This NIR-light-activated local hyperthermia and drug release presented the basis for combined chemotherapy and photothermal therapy (PTT) in antitumor treatment and displayed superb therapeutic efficacy. This pattern together with the high spatial precision imparted by laser triggering jointly contributed to the maximum combined antitumor efficacy to the tumor, while exhibiting minimal side effects on the normal tissues, as preliminarily verified in the in vivo experiment regarding the ability of PT@MFH to efficiently inhibit tumor growth in tumor-bearing model mice.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Animais , Linhagem Celular Tumoral , Raios Infravermelhos , Camundongos , Camundongos Endogâmicos BALB C , Micelas , Neoplasias/tratamento farmacológico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Fototerapia , Terapia Fototérmica , Polímeros
7.
Nat Commun ; 12(1): 6399, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737274

RESUMO

Targeting subcellular organelle with multilevel damage has shown great promise for antitumor therapy. Here, we report a core-shell type of nanoagent with iron (III) carboxylate metal-organic frameworks (MOFs) as shell while upconversion nanoparticles (UCNPs) as core, which enables near-infrared (NIR) light-triggered synergistically reinforced oxidative stress and calcium overload to mitochondria. The folate decoration on MOFs shells enables efficient cellular uptake of nanoagents. Based on the upconversion ability of UCNPs, NIR light mediates Fe3+-to-Fe2+ reduction and simultaneously activates the photoacid generator (pHP) encapsulated in MOFs cavities, which enables release of free Fe2+ and acidification of intracellular microenvironment, respectively. The overexpressed H2O2 in mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforce Fenton reactions for producing lethal hydroxyl radicals (•OH) while plasma photoacidification inducing calcium influx, leading to mitochondria calcium overload. The dual-mitochondria-damage-based therapeutic potency of the nanoagent has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.


Assuntos
Cálcio/metabolismo , Estruturas Metalorgânicas/farmacologia , Mitocôndrias/metabolismo , Células HeLa , Humanos , Radical Hidroxila/metabolismo , Raios Infravermelhos , Estruturas Metalorgânicas/química , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/efeitos da radiação , Nanoestruturas/química , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação
8.
Sci Adv ; 7(13)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33771861

RESUMO

To address long-standing issues with tumor penetration and targeting among cancer therapeutics, we developed an anticancer platelet-based biomimetic formulation (N+R@PLTs), integrating photothermal nanoparticles (N) and immunostimulator (R) into platelets (PLTs). Exploiting the aggregative properties of platelets and high photothermal capacity, N+R@PLTs functioned as an arsenal by targeting defective tumor vascular endothelial cells, accumulating in a positive feedback aggregation cascade at sites of acute vascular damage induced by N-generated local hyperthermia, and subsequently secreting nanosized proplatelets (nPLTs) to transport active components to deep tumor tissue. The immunostimulator augmented the immunogenicity of antigens released from ablated tumors, inducing a stronger immunological response to attack residual, metastatic, and recurrent tumors. Following activation by low-power near-infrared light irradiation, the photothermal and immunological components synergistically provide exceptionally high therapeutic efficacy across nine murine models that mimicked a range of clinical requirements, and, most notably, a sophisticated model based on humanized mouse and patient-derived tumor xenograft.

9.
Sci Adv ; 7(6)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33547068

RESUMO

The poor understanding of the complex multistep process taken by nanocarriers during the delivery process limits the delivery efficiencies and further hinders the translation of these systems into medicine. Here, we describe a series of six self-assembled nanocarrier types with systematically altered physical properties including size, shape, and rigidity, as well as both in vitro and in vivo analyses of their performance in blood circulation, tumor penetration, cancer cell uptake, and anticancer efficacy. We also developed both data and simulation-based models for understanding the influence of physical properties, both individually and considered together, on each delivery step and overall delivery process. Thus, beyond finding that nanocarriers that are simultaneously endowed with tubular shape, short length, and low rigidity outperformed the other types, we now have a suit of theoretical models that can predict how nanocarrier properties will individually and collectively perform in the multistep delivery of anticancer therapies.

10.
Anal Bioanal Chem ; 413(4): 1215-1224, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33386936

RESUMO

Hydrogen sulfide (H2S) typically plays biphasic biological roles in living organisms with subnormal H2S exerting cytoprotective effects such as participating in cardioprotective signaling pathways while H2S with higher-than-normal concentrations in localized tissues acting the opposite way such as inhibiting mitochondrial respiration. Such concentration-dependent biological and pathological roles of H2S with the wide involvement of mitochondria and the elusive feature of H2S definitely highlight the vital significance of fast and precise estimation of the physiological level of H2S in specific microenvironments, particularly within cellular mitochondria. In this work, we developed a new type of fluorescent probe (QcyCHO) featured with H2S-triggered off-to-on near-infrared (NIR) fluorescence conversion within ~ 10 min, limit of detection (LOD) down to 8.3 nM, and high recognition specificity over other similarly interfering species. The ideal mitochondrion-targeting ability, high recognition specificity over typical interfering substances and other physiologically relevant species, and the ability for mapping intracellular H2S in living cells of QcyCHO probe were also unequivocally confirmed, which imply its potential for shedding light on the biology of H2S and therapeutic development in H2S-associated diseases by identifying the specific physiological stimuli inducing H2S production and determining the levels of H2S at the location and time of stimulation.


Assuntos
Corantes Fluorescentes/química , Sulfeto de Hidrogênio/análise , Mitocôndrias/química , Células HeLa , Humanos , Microscopia Confocal , Microscopia de Fluorescência , Mitocôndrias/ultraestrutura , Imagem Óptica
11.
Talanta ; 219: 121354, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32887080

RESUMO

As a typical kind of endogenous reactive nitrogen species, peroxynitrite (ONOO-) is believed heavily involved in the pathogenesis of many diseases such as inflammation, neurodegenerative conditions, and cardiovascular disorders. Precisely estimating ONOO- level in cell compartments is crucial for unraveling the biological relevance of ONOO- and enabling effective control of ONOO--associated pathogenicity but suffers from serious difficulty owing to the daunting elusive features of ONOO-, namely nanomolar level physiological concentration and millisecond level biological half-life. A new fluorescent probe capable of detecting ONOO- with limit of detection down to 1.2 nM, response time less than 1s, and high recognition specificity over other similarly interfering species was developed in this work. For the probe constructed by conjugating an isatin moiety with an electron-withdrawing tricyanofuran (TCF) moiety, the former enabled a highly selective ONOO--mediated oxidative decarbonylation reaction while the latter significantly improved the electrophilicity of the 3-position carbonyl group of isatin moiety and therefore accelerate the ONOO--mediated nucleophilic attack, which eventually enabled prompt and efficient recognition reaction. For the decarbonylated product featured with a released primary aniline moiety, TCF acted as an acceptor for enabling an intramolecular charge transfer (ICT) process and the remarkable change in electronic feature upon reaction with ONOO-, which generated turn-on fluorescence with large contrast and therefore the basis for ONOO- sensing. The cell fluorescence imaging performed in this work definitely verified the capability of the probe for mapping intracellular ONOO-, despite the daunting elusive features of such physiological species.


Assuntos
Corantes Fluorescentes , Ácido Peroxinitroso , Fluorescência , Oxirredução
12.
Adv Mater ; 32(33): e2003563, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32627937

RESUMO

Nanozyme-based tumor catalytic therapy has attracted widespread attention in recent years. However, its therapeutic outcomes are diminished by many factors in the tumor microenvironment (TME), such as insufficient endogenous hydrogen peroxide (H2 O2 ) concentration, hypoxia, and immunosuppressive microenvironment. Herein, an immunomodulation-enhanced nanozyme-based tumor catalytic therapy strategy is first proposed to achieve the synergism between nanozymes and TME regulation. TGF-ß inhibitor (TI)-loaded PEGylated iron manganese silicate nanoparticles (IMSN) (named as IMSN-PEG-TI) are constructed to trigger the therapeutic modality. The results show that IMSN nanozyme exhibits both intrinsic peroxidase-like and catalase-like activities under acidic TME, which can decompose H2 O2 into hydroxyl radicals (•OH) and oxygen (O2 ), respectively. Besides, it is demonstrated that both IMSN and TI can regulate the tumor immune microenvironment, resulting in macrophage polarization from M2 to M1, and thus inducing the regeneration of H2 O2 , which can promote catalytic activities of IMSN nanozyme. The potent antitumor effect of IMSN-PEG-TI is proved by in vitro multicellular tumor spheroids (MCTS) and in vivo CT26-tumor-bearing mice models. It is believed that the immunomodulation-enhanced nanozyme-based tumor treatment strategy is a promising tool to kill cancer cells.


Assuntos
Biocatálise , Materiais Biomiméticos/farmacologia , Enzimas/metabolismo , Imunomodulação/efeitos dos fármacos , Nanomedicina , Nanoestruturas/química , Animais , Materiais Biomiméticos/química , Linhagem Celular Tumoral , Humanos , Camundongos , Microambiente Tumoral/efeitos dos fármacos
14.
Chem Sci ; 10(18): 4847-4853, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31183034

RESUMO

Although the antimonene (AM) nanomaterial is recently emerging as a new photothermal therapy (PTT) agent, its rapid degradation in physiological medium immensely limits its direct utilization. To this end, we herein engineered AM by the cooperation of dimension optimization, size control, and cell membrane (CM) camouflage. Compared with traditional AM nanosheets, the resulting AM nanoparticles (∼55 nm) cloaked with the CM (denoted as CmNPs) exhibited significantly improved stability and increased photothermal efficacy as well as superior tumor targeting capacity. After intravenous injection, the CmNPs enabled satisfactory photoacoustic/photothermal multimodal imaging at tumor sites. Meanwhile, the PTT together with the newly explored function of photodynamic therapy (PDT) achieved a potent combination therapy with few side effects. The maximized theranostic performance thus strongly recommends CmNPs as a safe and highly reliable modality for anticancer therapy.

15.
ACS Nano ; 13(5): 5662-5673, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31046234

RESUMO

As traditional anticancer treatments fail to significantly improve the prognoses, exploration of therapeutic modalities is urgently needed. Herein, a biomimetic magnetosome is constructed to favor the ferroptosis/immunomodulation synergism in cancer. This magnetosome is composed of an Fe3O4 magnetic nanocluster (NC) as the core and pre-engineered leukocyte membranes as the cloak, wherein TGF-ß inhibitor (Ti) can be loaded inside the membrane and PD-1 antibody (Pa) can be anchored on the membrane surface. After intravenous injection, the membrane camouflage results in long circulation, and the NC core with magnetization and superparamagnetism enables magnetic targeting with magnetic resonance imaging (MRI) guidance. Once inside the tumor, Pa and Ti cooperate to create an immunogenic microenvironment, which increases the amount of H2O2 in polarized M1 macrophages and thus promotes the Fenton reaction with Fe ions released from NCs. The generated hydroxyl radicals (•OH) subsequently induce lethal ferroptosis to tumor cells, and the exposed tumor antigen, in turn, improves the microenvironment immunogenicity. The synergism of immunomodulation and ferroptosis in such a cyclical manner therefore leads to potent therapeutic effects with few abnormalities, which supports the engineered magnetosomes as a promising combination modality for anticancer therapy.


Assuntos
Ferroptose/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Nanopartículas de Magnetita/química , Neoplasias/tratamento farmacológico , Antígenos de Neoplasias/farmacologia , Sinergismo Farmacológico , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/farmacologia , Fatores Imunológicos/química , Imunomodulação/efeitos dos fármacos , Nanopartículas de Magnetita/administração & dosagem , Magnetossomos/química , Magnetospirillum/efeitos dos fármacos , Neoplasias/patologia , Microambiente Tumoral/efeitos dos fármacos
16.
ACS Cent Sci ; 5(5): 796-807, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31139716

RESUMO

A novel cancer vaccine is developed by using Fe3O4 magnetic nanoclusters (MNCs) as the core and cancer cell membranes decorated with anti-CD205 as the cloak. Because of the superparamagnetism and magnetization of MNCs, it is first achieved for the magnetic retention of vaccine in the lymph nodes with a magnetic resonance imaging (MRI) guide, which opened the time window for antigen uptake by dendritic cells (DCs). Meanwhile, the camouflaged cancer cell membranes serve as a reservoir of various antigens, enabling subsequent multiantigenic response. Additionally, the decorated anti-CD205 direct more vaccine into CD8+ DCs, facilitating the major histocompatibility complex (MHC) I cross-presentation. These unique advantages together lead to a great proliferation of T cells with superior clonal diversity and cytotoxic activity. As a result, potent prophylactic and therapeutic effects with few abnormalities are observed on five different tumor models. Therefore, such a cancer-derived magnetosome with the integration of various recent nanotechnologies successfully demonstrates its promise for safe and high-performance cancer vaccination.

17.
Food Res Int ; 120: 130-140, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31000223

RESUMO

Food-sourced bioactive compounds have drawn much attention due to their health benefits such as anti-oxidant, anti-cancer, anti-diabetes and cardiovascular disease-preventing functions. However, the poor solubility, low stability and limited bioavailability of sensitive bioactive compounds greatly limited their application in food industry. Therefore, numbers of carriers were developed for improving their dispersibility, stability and bioavailability. This review addresses the digestion and absorption mechanisms of bioactive compounds in epithelial cells based on several well-known in vitro and in vivo models. Factors such as environmental stimuli, stomach conditions and mucus barrier influencing the utilization efficacy of the bioactive compounds are discussed. Delivery systems with enhanced utilization efficacy, such as complex coacervates, cross-linked polysaccharides, self-assembled micro-/nano-particles and Pickering emulsions are compared. It is a comprehensive multidisciplinary review which provides useful guidelines for application of bioactive compounds in food industry.


Assuntos
Sistemas de Liberação de Medicamentos , Ingredientes de Alimentos , Absorção Intestinal , Nutrientes/administração & dosagem , Polifenóis/administração & dosagem , Disponibilidade Biológica , Cápsulas , Emulsões , Excipientes , Alimentos , Indústria Alimentícia/métodos , Humanos , Nanopartículas
18.
Small ; 15(20): e1805544, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30924285

RESUMO

Many candidate anticancer drugs have suffered from their intrinsic hydrophobicity, which poses several obstacles for clinical application. To overcome this challenge and further improve the performance, herein a nanocrystal-based biomimetic formulation with a sandwich structure is developed. As the core, flake shaped nanocrystals (NCs) with high loading of the hydrophobic drug hydroxycamptothecin (HCPT) are synthesized via a mild nanoprecipitation process by exploring the template effect of serum albumin. Meanwhile, the camouflaged cancer cell membrane (CM) composed of plentiful membrane proteins endows the NCs with homotypic targeting capacity at tumor sites. In addition, the photosensitizer indocyanine green sandwiched between NCs and CM not only converts near infrared light to heat for photothermal treatment but also improves the dissolution of HCPT NCs for chemotherapy. These features corporately achieve the orchestration of chemo-photothermal combination therapy and completely inhibit tumor growth with few adverse effects, showing promise as a new modality for the utilization of hydrophobic drugs to treat cancer.


Assuntos
Membrana Celular/química , Interações Hidrofóbicas e Hidrofílicas , Hipertermia Induzida , Nanopartículas/química , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Terapia Combinada , Feminino , Humanos , Verde de Indocianina/uso terapêutico , Camundongos Endogâmicos BALB C , Nanopartículas/ultraestrutura , Distribuição Tecidual
19.
Nanomedicine (Lond) ; 14(5): 595-612, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30806584

RESUMO

AIM: To achieve enhanced anticancer efficacy by combined siPlk1 and curcumin (cur) therapy using α-lactalbumin (α-lac) nanocarrier delivery. MATERIALS & METHODS: α-Lac was partially hydrolyzed into amphiphilic peptides, and then self-assembled into nanospheres (NS). Cur was loaded into their hydrophobic core during the self-assembly process. siPlk1-SH was cross-linked with the endogenous cysteines on the NS. CRGDK peptide was conjugated on NS to target integrins overexpressed in HeLa cells. RESULTS & CONCLUSION: The Cur and siPlk1 coloaded NS formulations possessed an enhanced tumor targeting and antitumor properties. Drugs were responsively released from disulfide bonds cross-linked RGD-NS/Cur/siPlk1 corresponding to the high intracellular glutathione concentrations of cancer cells. Both in vitro cell viability experiments and in vivo antitumor evaluations demonstrated that the codelivered nanosphere platform exhibited excellent tumor targeting and synergistic antitumor efficacy.


Assuntos
Curcumina/química , Lactalbumina/química , Nanosferas/química , Animais , Antineoplásicos/química , Composição de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Feminino , Citometria de Fluxo , Células HeLa , Humanos , Lisossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Micelas , RNA Mensageiro/genética , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Ensaios Antitumorais Modelo de Xenoenxerto
20.
ACS Nano ; 13(1): 260-273, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30616348

RESUMO

As a type of programmed cell death, ferroptosis is distinct from apoptosis. The combination of the two thus provides a promising modality with which to significantly improve anticancer treatment efficacy. To fully utilize this combination, we herein designed a nanolongan delivery system, which possessed a typical structure of one core (up-conversion nanoparticles, UCNP) in one gel particle (Fe3+ cross-linked oxidized starch) with multiple on-demand conversions. The charge conversion of the nanolongan surface in a slightly acidic microenvironment enhanced circulation time for utilizing the enhanced permeability and retention effect, enabled efficient uptake by tumor cells, and induced subsequently lysosomal escape. As the core component, the UCNP with light conversion from near-infrared light to ultraviolet light circumvented the impediment of limited penetration depth and enabled the reduction of Fe3+ to Fe2+. Accordingly, gel networks of nanolongan could be deconstructed due to this valence conversion, leading to the rapid release of Fe2+ and doxorubicin (Dox). In this case, the Fenton reaction between Fe2+ and intracellular H2O2 generated potent reactive oxygen species for ferroptosis, while the co-released Dox penetrated into nucleus and induced apoptosis in a synergistic way. As a result, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that our nanolongan could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Ferroptose , Nanopartículas Metálicas/química , Animais , Linhagem Celular Tumoral , Portadores de Fármacos/efeitos adversos , Portadores de Fármacos/efeitos da radiação , Liberação Controlada de Fármacos , Hemólise , Raios Infravermelhos , Ferro/metabolismo , Lisossomos/metabolismo , Anidridos Maleicos/química , Nanopartículas Metálicas/efeitos adversos , Nanopartículas Metálicas/efeitos da radiação , Camundongos , Oxirredução , Coelhos , Amido/análogos & derivados , Raios Ultravioleta
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...