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1.
Adv Healthc Mater ; 12(30): e2301592, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37681300

RESUMO

Inhibition of oxidative stress and inflammatory responses caused by secondary injury following traumatic spinal cord injury (SCI) is an attractive strategy in treating traumatic SCI. However, the efficacy of drugs is severely limited owing to the poor penetration of the blood spinal cord barrier (BSCB). Here, inspired by cell chemotaxis and related chemokines production at the lesion sites of SCI, the microglial membrane is selected to construct a drug delivery system with the ability to cross the BSCB and target the lesions. PR@MM is prepared based on the assembly of polylactic-co-glycolic acid (PLGA) and resveratrol (RSV) followed by microglial membrane (MM) coating. Compared to that of the uncoated nanoparticles, the enrichment of PR@MM at the lesion sites of SCI increases, which is beneficial to achieve lesion targeting of RSV and exert therapeutic functions. Both in vitro and in vivo experiments demonstrate that PR@MM has the ability to scavenge reactive oxygen species and anti-inflammatory effects, which ultimately promotes the recovery of locomotory function after SCI. Therefore, this microglial membrane-based drug delivery system provides a promising biomimetic nanomedicine for targeted therapy for SCI.


Assuntos
Fármacos Neuroprotetores , Traumatismos da Medula Espinal , Humanos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Microglia/patologia , Biomimética , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia
2.
Nat Commun ; 13(1): 4214, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35864093

RESUMO

Glioblastoma multiforme (GBM) is an aggressive brain cancer with a poor prognosis and few treatment options. Here, building on the observation of elevated lactate (LA) in resected GBM, we develop biomimetic therapeutic nanoparticles (NPs) that deliver agents for LA metabolism-based synergistic therapy. Because our self-assembling NPs are encapsulated in membranes derived from glioma cells, they readily penetrate the blood-brain barrier and target GBM through homotypic recognition. After reaching the tumors, lactate oxidase in the NPs converts LA into pyruvic acid (PA) and hydrogen peroxide (H2O2). The PA inhibits cancer cell growth by blocking histones expression and inducing cell-cycle arrest. In parallel, the H2O2 reacts with the delivered bis[2,4,5-trichloro-6-(pentyloxycarbonyl)phenyl] oxalate to release energy, which is used by the co-delivered photosensitizer chlorin e6 for the generation of cytotoxic singlet oxygen to kill glioma cells. Such a synergism ensures strong therapeutic effects against both glioma cell-line derived and patient-derived xenograft models.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Nanopartículas , Biomimética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Peróxido de Hidrogênio
3.
ACS Appl Mater Interfaces ; 14(4): 5112-5121, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35048696

RESUMO

Type-I photodynamic therapy (PDT) with less oxygen consumption shows great potential for overcoming the vicious hypoxia typically observed in solid tumors. However, the development of type-I PDT is hindered by insufficient radical generation and the ambiguous design strategy of type-I photosensitizers (PSs). Therefore, developing highly efficient type-I PSs and unveiling their structure-function relationship are still urgent and challenging. Herein, we develop two phenanthro[9,10-d]imidazole derivatives (AQPO and AQPI) with aggregation-induced emission (AIE) characteristics and boost their reactive oxygen species (ROS) generation efficiency by reducing singlet-triplet splitting (ΔEST). Both AQPO and AQPI show ultrasmall ΔEST values of 0.09 and 0.12 eV, respectively. By incorporating electron-rich anisole, the categories of generated ROS by AIE PSs are changed from type-II (singlet oxygen, 1O2) to type-I (superoxide anion radical, O2•- and hydroxyl radical, •OH). We demonstrate that the assembled AQPO nanoparticles (NPs) achieve a 3.2- and 2.9-fold increase in the O2•- and •OH generation efficiencies, respectively, compared to those of AQPI NPs (without anisole) in water, whereas the 1O2 generation efficiency of AQPO NPs is lower (0.4-fold) than that of AQPI NPs. The small ΔEST and anisole group endow AQPO with an excellent capacity for type-I ROS generation. In vitro and in vivo experiments show that AQPO NPs achieve an excellent hypoxia-overcoming PDT effect by efficiently eliminating tumor cells upon white light irradiation with good biosafety.


Assuntos
Imidazóis/uso terapêutico , Neoplasias/tratamento farmacológico , Fenantrolinas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Hipóxia Tumoral/efeitos dos fármacos , Células A549 , Animais , Portadores de Fármacos/química , Feminino , Humanos , Imidazóis/síntese química , Imidazóis/efeitos da radiação , Luz , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células NIH 3T3 , Nanopartículas/química , Fenantrolinas/síntese química , Fenantrolinas/efeitos da radiação , Fosfatidiletanolaminas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Polietilenoglicóis/química
4.
Mater Horiz ; 8(2): 571-576, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821273

RESUMO

We report the first demonstration using a stable π-radical as a versatile photosensitizer for hypoxia-overcoming photodynamic therapy. After self-assembling the radical molecules into radical nanoparticles (NPs), the NPs show good water dispersibility, good biocompatibility, broad near-infrared (NIR) absorption and emission at ∼800 nm. Significantly, the radical NPs remain stable in various biological mediums, after 100 days exposure to the ambient environment, and even after long-term laser irradiation, which is superior to many reported radical-based materials. More importantly, upon 635 nm laser irradiation, sufficient superoxide radical (O2-˙) generation and in vitro cytotoxicity were observed addressing the most important hurdle for successful PDT in the oxygen-deficient tumor microenvironment. In addition, the radical NPs are also demonstrated to have effective in vivo PDT efficacy, and excellent biosafety.


Assuntos
Nanopartículas , Fotoquimioterapia , Humanos , Hipóxia/tratamento farmacológico , Oxigênio , Fármacos Fotossensibilizantes/farmacologia
5.
Adv Mater ; 33(38): e2102799, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34319622

RESUMO

There has been much recent progress in the development of photothermal agents (PTAs) for biomedical and energy applications. Synthesis of organic PTAs typically involves noble metal catalysts and high temperatures. On the other hand, photochemical synthesis, as an alternative and green chemical technology, has obvious merits such as low cost, energy efficiency, and high yields. However, photochemical reactions have rarely been employed for the synthesis of PTAs. Herein, a facile and high-yield photochemical reaction is exploited for synthesizing nonplanar small molecules (NSMs) containing strong Michler's base donors and a tricyanoquinodimethane acceptor as high-performance PTAs. The synthesized NSMs show interesting photophysical properties including good absorption for photons of over 1000 nm wavelength, high near-infrared extinction coefficients, and excellent photothermal performance. Upon assembling the NSMs into nanoparticles (NSMN), they exhibit good biocompatibility, high photostability, and excellent photothermal conversion efficiency of 75%. Excited-state dynamic studies reveal that the NSMN has ultrafast nonradiative decay after photoexcitation. With these unique properties, the NSMN achieves efficient in vivo photoacoustic imaging and photothermal tumor ablation. This work demonstrates the superior potential of photochemical reactions for the synthesis of high-performance molecular PTAs.


Assuntos
Fototerapia , Nanomedicina Teranóstica , Nanopartículas , Técnicas Fotoacústicas
6.
ACS Appl Mater Interfaces ; 13(26): 30274-30283, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34170100

RESUMO

In this work, an iron self-boosting polymer nanoenzyme was prepared by using pyrrole-3-carboxylic acid as a monomer and iron as an oxidizing agent via a simple and one-step method [hereafter referred to as FePPy nanoparticles (NPs)]. In fact, researchers previously paid negligible attention on the iron element during the polymerization reaction of polypyrrole, thus the intrinsically catalytic functions and enzymatic activities of the high iron content (wt %: 21.11%) are ignored and not fully explored. As expected, results demonstrate that the as-synthesized FePPy NPs can decompose H2O2 to generate hydroxyl radicals (•OH) which exhibit enzyme characteristics, further inducing a nonapoptotic ferroptosis pathway. Moreover, the nanoenzyme shows impressive photothermal properties which can accelerate the Fenton reactions to enhance ferroptosis. The combined photothermal and ferroptosis therapy of FePPy NPs was found to have high efficacy. With the properties of easy synthesis, high efficacy, and good biocompatibility, the FePPy NPs are considered as potential agents for cancer treatments.


Assuntos
Antineoplásicos/uso terapêutico , Ferroptose/efeitos dos fármacos , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/efeitos da radiação , Ácidos Carboxílicos/química , Ácidos Carboxílicos/efeitos da radiação , Ácidos Carboxílicos/uso terapêutico , Catálise , Feminino , Células HeLa , Humanos , Peróxido de Hidrogênio/química , Radical Hidroxila/metabolismo , Ferro/química , Ferro/efeitos da radiação , Luz , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Polímeros/química , Polímeros/efeitos da radiação , Polímeros/uso terapêutico , Pirróis/química , Pirróis/efeitos da radiação , Pirróis/uso terapêutico , Temperatura
7.
Chem Commun (Camb) ; 57(40): 4902-4905, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33870972

RESUMO

A bromine-substituted thermally activated delayed fluorescent (TADF) molecule AQCzBr2 is designed with both small singlet-triplet splitting (ΔEST) and increased spin-orbit coupling (SOC) to boost intersystem crossing (ISC) for singlet oxygen generation. AQCzBr2 nanoparticles (NPs) demonstrate high productivity of singlet oxygen generation (ΦΔ = 0.91) which allows highly efficient photodynamic therapy toward cancer cells.

8.
ACS Appl Mater Interfaces ; 13(14): 15983-15991, 2021 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-33788531

RESUMO

Organic small molecule-based phototheranostics hold great promise for clinical translation by virtue of their distinct chemical structure, easy reproducibility, and high purity. However, reported molecular agents typically have relatively low optical absorbances, particularly over the near-infrared (NIR) region, and this limits their phototheranostic performance. Herein, we first exploit a diradicaloid molecular structure for enhancing NIR absorption to facilitate efficient photoacoustic imaging (PAI)-guided photothermal therapy (PTT). The donor-acceptor interaction in the diradicaloid molecule (DRM) leads to strong charge transfer resulting on obvious diradical characteristics, which is beneficial for NIR absorption. The DRM possesses excellent light-harvesting ability, with a mass extinction coefficient of ∼220 L g-1 cm-1, which is much higher than those (∼5-100 L g-1 cm-1) of typical organic molecules. After assembling into nanoparticles, they show good water dispersibility, good photostability, and impressive performance for PAI-guided PTT in vitro and in vivo. The impressive in vitro and in vivo performances show that developing small molecules with diradicaloid structures can be an effective approach for enhancing NIR harvesting capability for biomedical applications.


Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Terapia Fototérmica , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Nanomedicina Teranóstica/métodos , Células 3T3 , Células A549 , Animais , Materiais Biocompatíveis , Humanos , Camundongos , Nanopartículas
9.
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.

10.
Adv Mater ; 33(7): e2005562, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33432702

RESUMO

Extracellular vesicles (EVs) hold great potential in both disease treatment and drug delivery. However, accurate drug release from EVs, as well as the spontaneous treatment effect cooperation of EVs and drugs at target tissues, is still challenging. Here, an engineered self-activatable photo-EV for synergistic trimodal anticancer therapy is reported. M1 macrophage-derived EVs (M1 EVs) are simultaneously loaded with bis[2,4,5-trichloro-6-(pentyloxycarbonyl) phenyl] oxalate (CPPO), chlorin e6 (Ce6), and prodrug aldoxorubicin (Dox-EMCH). After administration, the as-prepared system actively targets tumor cells because of the tumor-homing capability of M1 EVs, wherein M1 EVs repolarize M2 to M1 macrophages, which not only display immunotherapy effects but also produce H2 O2 . The reaction between H2 O2 and CPPO generates chemical energy that activates Ce6, creating both chemiluminescence for imaging and singlet oxygen (1 O2 ) for photodynamic therapy (PDT). Meanwhile, 1 O2 -induced membrane rupture leads to the release of Dox-EMCH, which is then activated and penetrates the deep hypoxic areas of tumors. The synergism of immunotherapy, PDT, and chemotherapy results in potent anticancer efficacy, showing great promise to fight cancers.


Assuntos
Antineoplásicos/química , Doxorrubicina/análogos & derivados , Portadores de Fármacos/química , Vesículas Extracelulares/química , Hidrazonas/química , Macrófagos/química , Oxalatos/química , Porfirinas/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Clorofilídeos , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Feminino , Humanos , Hidrazonas/farmacologia , Imunoterapia , Masculino , Camundongos , Oxalatos/farmacologia , Processos Fotoquímicos , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia , Oxigênio Singlete/metabolismo
11.
ACS Nano ; 14(8): 9917-9928, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32706236

RESUMO

Effective multimodality phototheranostics under deep-penetration laser excitation is highly desired for tumor medicine, which is still at a deadlock due to lack of versatile photosensitizers with absorption located in the long-wavelength region. Herein, we demonstrate a stable organic photosensitizer nanoparticle based on molecular engineering of benzo[c]thiophene (BT)-based photoactivated molecules with strong wavelength-tunable absorption in the near-infrared region. Via molecular design, the absorption and singlet oxygen generation of BT molecules would be reliably tuned. Importantly, the nanoparticles with a red-shifted absorption peak of 843 nm not only show over 10-fold reactive oxygen species yield compared with indocyanine green but also demonstrate a notable photothermal effect and photoacoustic signal upon 808 nm excitation. The in vitro and in vivo experiments substantiate good multimodal anticancer efficacy and imaging performance of BT theranostics. This work provides an organic photosensitizer nanoparticle with long-wavelength excitation and high photoenergy conversion efficiency for multimodality phototherapy.


Assuntos
Nanopartículas , Fármacos Fotossensibilizantes , Fototerapia , Espécies Reativas de Oxigênio , Nanomedicina Teranóstica
12.
J Control Release ; 326: 131-139, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-32580043

RESUMO

As the combination of photothermal therapy (PTT) with immunotherapy provides an effective strategy in cancer treatment, a magnetic nanoparticle delivery system was constructed to load indocyanine green (ICG) and immunostimulator R837 hydrochloride (R837) for spatio-temporally PTT/immunotherapy synergism in cancer. This delivery system is composed of Fe3O4 magnetic nanoparticles (MPs) as the core to load ICG and polyethylene glycol polyphenols (DPA-PEG) as the coating layer to load R837, which formed R837 loaded polyphenols coating ICG loaded magnetic nanoparticles (MIRDs). After intravenous injection, the formed MIRDs resulted in long circulation, magnetic resonance imaging (MRI) guides, and magnetic targeting. Once targeting to the tumor, the MIRDs with the near-infrared (NIR) irradiation caused tumor ablation and resulted in tumor-associated antigens releasing to induce the body's immunological response, which was markedly improved it to attack the tumors with the R837 releasing from the outer DPA-PEG. In this case, the synergism of the PTT and immunotherapy inhibited tumor growth, metastasis and recurrence, which resulted in potent anticancer therapeutic effects with few side effect.


Assuntos
Nanopartículas de Magnetita , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Imunoterapia , Verde de Indocianina , Fototerapia , Polifenóis
13.
Biomater Sci ; 8(8): 2283-2288, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32163067

RESUMO

Highly efficient tumor-targeted therapy remains a great challenge due to the complexity and heterogeneity of tumor tissues. Herein, we developed an in vivo two-step tumor-targeting strategy by combining metabolic lipid-engineering with a stain-promoted azide-alkyne 1,3-dipolar cycloaddition (SPAAC) reaction, independent of the tumor microenvironment and cell phenotype. Firstly, exogenously-supplied azidoethyl-cholines (AECho) were metabolically incorporated into the cell membranes in tumor tissues through the intrinsic biosynthesis of phosphatidylcholine. The pre-inserted and accumulated azido groups (N3) could subsequently serve as 'artificial chemical receptors' for the specific anchoring of dibenzocyclooctyne (DBCO) modified biomimetic nanoparticles (DBCO-RBCG@ICG) via in situ click chemistry, resulting in significantly enhanced tumor-targeting and then an improved photothermal therapy effect. Such a two-step targeting strategy based on these cutting-edge techniques provided new insights into the universal and precise functionalization of living tissues for site-specific drug delivery in the diagnosis and treatment of various diseases.


Assuntos
Sistemas de Liberação de Medicamentos , Membrana Eritrocítica , Animais , Linhagem Celular Tumoral , Colina/administração & dosagem , Colina/química , Química Click , Corantes/administração & dosagem , Corantes/química , Humanos , Verde de Indocianina/administração & dosagem , Verde de Indocianina/química , Lipídeos/administração & dosagem , Lipídeos/química , Engenharia Metabólica , Camundongos , Neoplasias/terapia , Fototerapia
14.
Chem Sci ; 11(8): 2155-2160, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34123305

RESUMO

Precise activation of prodrugs in tumor tissues is critical to ensuring specific antitumor efficacy, meanwhile reducing the serious adverse effects. Here, a spatiotemporally controlled prodrug activation strategy was provided by integrating the inverse electron demand Diels-Alder (IEDDA) reaction with two tumor-microenvironment-responsive nanovehicles. The prodrug (Dox-TCO) and [4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanamine (Tz) were separately camouflaged into low pH and matrix metalloproteinase 2 (MMP-2) sensitive micellar nanoparticles. After systemic administration, only in the tumor tissues could both the nanovehicles dissociate via responding to two special tumor microenvironments, with Dox-TCO and Tz released and then immediately triggering the prodrug activation through the IEDDA reaction. The hierarchically regulated and locally confined Dox liberation led to dramatically decreased side-effects that were much lower than those of the clinical Doxorubicin Hydrochloride Liposomal Injection (Doxil), while the antitumor therapeutic effect was potent.

16.
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.

17.
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
18.
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.

19.
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
20.
ACS Nano ; 13(2): 1469-1478, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30763076

RESUMO

Although adoptive T-cell therapy has been successful in hematological malignancy treatment, its application in solid tumors remains a great challenge. Here, using a pH-sensitive benzoic-imine bond and inverse electron-demand Diels-Alder cycloaddition, we prepared magnetic nanoclusters (NCs) armed with responsive PD-1 antibody (aP), which could then bind onto effector T cells due to their PD-1 expression. After adoptive transfer, the magnetization and superparamagnetism of NCs enabled us to magnetically recruit effector T cells and aP simultaneously to tumor sites with MRI guidance. Owing to the acidic intratumoral microenvironment, the benzoic-imine bond then hydrolyzed, leading to the release of aP. The therapeutic effects of adoptive T cells and free aP could thus be spatiotemporally coupled. As a result, we achieved inhibition of tumor growth with few side effects, demonstrating the great promise of such a chemical approach for safe and high-performance adoptive T-cell therapy against solid tumors.


Assuntos
Anticorpos/química , Anticorpos/imunologia , Imunoterapia Adotiva/métodos , Receptor de Morte Celular Programada 1/imunologia , Linfócitos T/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Concentração de Íons de Hidrogênio , Marcação In Situ das Extremidades Cortadas , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL
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