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1.
J Mater Chem B ; 12(16): 4039-4052, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38591157

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a disease with high incidence and poor prognosis. The conventional treatment involves radiotherapy and chemotherapy, but chemotherapeutic agents are often associated with side effects, i.e., cytotoxicity to nontumor cells. Therefore, there is an urgent need for the development of novel therapeutic strategies for ccRCC. We synthesized spherical P/TiO2 nanoparticles (P/TiO2 NPs) by vaporization phosphorization (VP). X-ray photoelectron spectroscopy (XPS) and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS) analyses confirmed that the anatase TiO2 surface was successfully doped with phosphorus and produced a large number of oxygen vacancies (OV). Serving as a photosensitizer, P/TiO2 NPs not only extended the photoresponse range to the near-infrared II region (NIR II) but also introduced a donor energy level lower than the TiO2 conduction band, narrowing the band gap, which could facilitate the migration of photogenerated charges and trigger the synergistic treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). During NIR irradiation in vitro, the P/TiO2 NPs generated local heat and various oxygen radicals, including 1O2, ˙O2-, H2O2, and ˙OH, which damaged the ccRCC cells. In vivo, administration of the P/TiO2 NPs + NIR reduced the tumor volume by 80%, and had the potential to inhibit tumor metastasis by suppressing intratumor neoangiogenesis. The P/TiO2 NPs showed superior safety and efficacy relative to the conventional chemotherapeutic agent used in ccRCC treatment. This study introduced an innovative paradigm for renal cancer treatment, highlighting the potential of P/TiO2 NPs as safe and effective nanomaterials and presenting a compelling new option for clinical applications in anticancer therapy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Nanocompostos , Fósforo , Fotoquimioterapia , Terapia Fototérmica , Titânio , Titânio/química , Titânio/farmacologia , Fósforo/química , Humanos , Animais , Nanocompostos/química , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Camundongos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Camundongos Endogâmicos BALB C , Ensaios de Seleção de Medicamentos Antitumorais , Tamanho da Partícula , Linhagem Celular Tumoral
2.
J Mater Chem B ; 12(17): 4097-4117, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38587869

RESUMO

Single phototherapy and immunotherapy have individually made great achievements in tumor treatment. However, monotherapy has difficulty in balancing accuracy and efficiency. Combining phototherapy with immunotherapy can realize the growth inhibition of distal metastatic tumors and enable the remote monitoring of tumor treatment. The development of nanomaterials with photo-responsiveness and anti-tumor immunity activation ability is crucial for achieving photo-immunotherapy. As immune adjuvants, photosensitizers and photothermal agents, manganese-based nanoparticles (Mn-based NPs) have become a research hotspot owing to their multiple ways of anti-tumor immunity regulation, photothermal conversion and multimodal imaging. However, systematic studies on the synergistic photo-immunotherapy applications of Mn-based NPs are still limited; especially, the green synthesis and mechanism of Mn-based NPs applied in immunotherapy are rarely comprehensively discussed. In this review, the synthesis strategies and function of Mn-based NPs in immunotherapy are first introduced. Next, the different mechanisms and leading applications of Mn-based NPs in immunotherapy are reviewed. In addition, the advantages of Mn-based NPs in synergistic photo-immunotherapy are highlighted. Finally, the challenges and research focus of Mn-based NPs in combination therapy are discussed, which might provide guidance for future personalized cancer therapy.


Assuntos
Imunoterapia , Manganês , Humanos , Manganês/química , Manganês/farmacologia , Imunoterapia/métodos , Fototerapia/métodos , Química Verde , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Animais , Nanoestruturas/química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Tamanho da Partícula
3.
Angew Chem Int Ed Engl ; 63(27): e202402028, 2024 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-38656658

RESUMO

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors.


Assuntos
Antineoplásicos , Complexos de Coordenação , Raios Infravermelhos , Fótons , Tiofenos , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Tiofenos/química , Tiofenos/farmacologia , Camundongos , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Rutênio/química , Rutênio/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Terapia Fototérmica , Irídio/química , Estrutura Molecular , Apoptose/efeitos dos fármacos
4.
ACS Appl Mater Interfaces ; 14(1): 474-483, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34978185

RESUMO

The nonselectivity of phototherapy and the hydrophobicity of phototherapy agents limit their application in the treatment of antibiotic-resistant bacteria. In this work, ß-cyclodextrin-derivative-functionalized graphene oxide (GO)/graphitic carbon nitride (g-C3N4) antibacterial materials (CDM/GO/CN) were designed and synthesized. CN is used as a photosensitizer for photodynamic therapy (PDT) and GO as a photothermal agent for photothermal therapy (PTT). In addition, the supramolecular host-guest complex on the substrate can not only increase the inherent water solubility of the substrate and reduce the aggregation of the photosensitizer/photothermal agent but also manipulate the interaction between the photosensitizer/photothermal agent and bacteria to capture specific bacteria. The hyperthermia caused by PTT denatures proteins on the cell membrane, allowing reactive oxygen species (ROS) to enter the cell better and kill bacteria. The specific capture of Escherichia coli CICC 20091 by mannose significantly improves the sterilization efficiency and reduces side effects. The synergistic antibacterial agent shows excellent antibacterial efficacy of over 99.25% against E. coli CICC 20091 after 10 min of 635 + 808 nm dual-light irradiation. Moreover, cell proliferation experiments show that the composite material has good biocompatibility, expected to have applications in bacterial infections.


Assuntos
Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Grafite/farmacologia , Compostos de Nitrogênio/farmacologia , Fármacos Fotossensibilizantes/farmacologia , beta-Ciclodextrinas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Linhagem Celular , Escherichia coli/efeitos dos fármacos , Grafite/química , Humanos , Teste de Materiais , Testes de Sensibilidade Microbiana , Compostos de Nitrogênio/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , beta-Ciclodextrinas/química
5.
Chem Commun (Camb) ; 58(14): 2247-2258, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35083992

RESUMO

Combinational photoimmunotherapy (PIT) is considered to be an ideal strategy for the treatment of highly recurrent and metastatic cancer, because it can ablate the primary tumor and provide in situ an autologous tumor vaccine to induce the host immune response, ultimately achieving the goal of controlling tumor growth and distal metastasis. Significant efforts have been devoted to enhancing the immune response caused by phototherapy-eliminated tumors. Recently, supramolecular PIT nanoagents based on precise peptide self-assembly design have been employed to improve the efficacy of photoimmunotherapy by utilizing the stability, targeting capability and flexibility of drugs, increasing tumor immunogenicity and realizing the synergistic amplification of immune effects through multiple pathways and collaborative strategy. This review summarizes peptide-based supramolecular PIT nanoagents for phototherapy-synergized cancer immunotherapy and its progress in enhancing the effect of photoimmunotherapy, especially focusing on the design of peptide-based PIT nanoagents, the progress of bioactive peptides combined photoimmunotherapy, and the synergistic immune-response mechanism.


Assuntos
Antineoplásicos/farmacologia , Imunoterapia , Neoplasias/terapia , Peptídeos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Antineoplásicos/síntese química , Antineoplásicos/química , Humanos , Substâncias Macromoleculares/síntese química , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Peptídeos/síntese química , Peptídeos/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química
6.
J Am Chem Soc ; 143(49): 20828-20836, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34860505

RESUMO

In recent years, cancer phototherapy has been extensively studied as noninvasive cancer treatment. To present efficient recognition toward cancer cells, most photosensitizers (PSs) are required to couple with tumor-targeted ligands. Interestingly, the heptamethine cyanine IR780 displays an intrinsic tumor-targeted feature even without modification. However, the photothermal efficacy and photostability of IR780 are not sufficient enough for clinical use. Herein, we involve a twisted structure of tetraphenylethene (TPE) between two molecules of IR780 to improve the photothermal conversion efficiency (PCE). The obtained molecule T780T shows strong near-infrared (NIR) fluorescence and improved PCE (38.5%) in the dispersed state. Also, the photothermal stability and ROS generation capability of T780T at the NIR range (808 nm) are both promoted. In the aqueous phase, the T780T was formulated into uniform nanoaggregates (∼200 nm) with extremely low fluorescence and PTT response, which would reduce in vivo imaging background and side effect of PTT response in normal tissues. After intravenous injection into tumor-bearing mice, the T780T nanoaggregates display high tumor accumulation and thus remarkably inhibit the tumor growth. Moreover, the enhanced photostability of the T780T allows for twice irradiation after one injection and leads to more significant tumor inhibition. In summary, our study presents a tumor-targeted small-molecule PS for efficient cancer therapy and brings a new design of heptamethine cyanine PS for potential clinical applications.


Assuntos
Antineoplásicos/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Indóis/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Estilbenos/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Linhagem Celular Tumoral , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Humanos , Indóis/síntese química , Indóis/efeitos da radiação , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Neoplasias/diagnóstico por imagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Estilbenos/síntese química , Estilbenos/efeitos da radiação
7.
ACS Appl Mater Interfaces ; 13(49): 58422-58433, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34855366

RESUMO

Despite the unique ability of lanthanide-doped upconversion nanoparticles (UCNPs) to convert near-infrared (NIR) light to high-energy UV-vis radiation, low quantum efficiency has rendered their application unpractical in biomedical fields. Here, we report anatase titania-coated plasmonic gold nanorods decorated with UCNPs (Au NR@aTiO2@UCNPs) for combinational photothermal and photodynamic therapy to treat cancer. Our novel architecture employs the incorporation of an anatase titanium dioxide (aTiO2) photosensitizer as a spacer and exploits the localized surface plasmon resonance (LSPR) properties of the Au core. The LSPR-derived near-field enhancement induces a threefold boost of upconversion emissions, which are re-absorbed by neighboring aTiO2 and Au nanocomponents. Photocatalytic experiments strongly infer that LSPR-induced hot electrons are injected into the conduction band of aTiO2, generating reactive oxygen species. As phototherapeutic agents, our hybrid nanostructures show remarkable in vitro anticancer effect under NIR light [28.0% cancer cell viability against Au NR@aTiO2 (77.3%) and UCNP@aTiO2 (98.8%)] ascribed to the efficient radical formation and LSPR-induced heat generation, with cancer cell death primarily following an apoptotic pathway. In vivo animal studies further confirm the tumor suppression ability of Au NR@aTiO2@UCNPs through combinatorial photothermal and photodynamic effect. Our hybrid nanomaterials emerge as excellent multifunctional phototherapy agents, providing a valuable addition to light-triggered cancer treatments in deep tissue.


Assuntos
Antineoplásicos/farmacologia , Glioblastoma/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/química , Glioblastoma/metabolismo , Glioblastoma/patologia , Ouro/administração & dosagem , Ouro/química , Humanos , Elementos da Série dos Lantanídeos/administração & dosagem , Elementos da Série dos Lantanídeos/química , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/administração & dosagem , Nanopartículas/química , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Imagem Óptica , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Titânio/administração & dosagem , Titânio/química
8.
J Mater Chem B ; 9(48): 9932-9945, 2021 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-34842269

RESUMO

An integration combination of phototherapy and chemotherapy to treat carcinoma, solving the inner limitation of individual-modal chemical agent-based therapy or phototherapy, emerges to be a strategy with high prospects for achieving synergistic curative effects. The dye IR780-iodide (IR780) close to infrared radiation is a phototherapy agent with high prospects. However, it is limited in its clinical applications due to poor solubility in water. While epigallocatechin-3-gallate (EGCG), naturally resourced green tea polyphenol, has been extensively proven with intrinsic antitumor activity, but it is largely restricted by its low bioavailability in vivo. Hence, novel multiple-function nanoparticles comprising hyaluronic acid (HA) and IR780 were proposed to deliver EGCG, defined as EGCG@THSI nano-scale particles (EGCG@THSI NPs), thereby rapidly solving limitations of EGCG and IR780. Amphiphilic nano-scale carrier was prepared by triphenylphosphine (TPP), hyaluronic acid (HA), cystamine, and IR780, termed as TPP-HA-SS-IR780, and EGCG was loaded into the amphiphilic copolymer by self-assembly. TPP-HA-SS-IR780 endowed the as-synthesized EGCG@THSI NPs with excellent TPP-mediated mitochondrial-targeted and glutathione-triggered rapid drug release properties. As impacted by the integration of phototherapy and chemotherapy, the EGCG@THSI NPs under NIR laser irradiation showed a prominent anti-tumor effect. Taken together, this study presented a multiple-function nano-scale carrier platform with high prospects in improving the therapeutic efficacy of anti-carcinoma drugs.


Assuntos
Antineoplásicos/farmacologia , Catequina/análogos & derivados , Corantes Fluorescentes/farmacologia , Indóis/farmacologia , Iodetos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Terapia Fototérmica , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Catequina/química , Catequina/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Indóis/química , Iodetos/química , Teste de Materiais , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estrutura Molecular , Nanopartículas/química , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Peixe-Zebra
9.
ACS Appl Mater Interfaces ; 13(47): 55928-55938, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34786942

RESUMO

The synergy of chemodynamic therapy (CDT) and photothermal therapy (PTT) can improve anticancer efficacy, while the limited diffusion distance and the short lifetime of •OH still greatly restrict the therapeutic efficacy of PTT-CDT. Herein, MoS2@PDA-Fe@PEG/TPP (MPFPT) nanosheets (NSs) with mitochondria-targeting ability were reported for enhanced PTT-CDT synergistic oncotherapy. MPFPT NSs were prepared by covalent modification of poly(ethylene glycol) (PEG) and triphenylphosphonium (TPP) on polydopamine (PDA)-Fe3+coated MoS2 NSs. Co-localization experiments showed that MPFPT NSs can efficiently target mitochondria via the direction of TPP. Moreover, MPFPT NSs have good photothermal performance in the second near-infrared (NIR-II) region and can greatly accelerate the Fenton reaction from H2O2 to generate more hydroxyl radicals (•OH). In vitro experimental results showed that MPFPT NSs have improved therapeutic efficacy to cancer cells than similar MoS2-based nanoagents without mitochondria-targeting units, which can be attributed to the short distance between mitochondria and MPFPT NSs and the efficient damage of mitochondria by in situ generated •OH. In the 4T1 tumor-bearing mice model, MPFPT NSs demonstrated significantly enhanced therapeutic efficacy by PTT-CDT, suggesting the superiority of the mitochondria-targeting strategy. This study reveals that mitochondria-targeting MPFPT NSs are promising nanoagents for oncotherapy.


Assuntos
Antineoplásicos/farmacologia , Dissulfetos/farmacologia , Mitocôndrias/efeitos dos fármacos , Molibdênio/farmacologia , Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Terapia Fototérmica , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dissulfetos/química , Ensaios de Seleção de Medicamentos Antitumorais , Raios Infravermelhos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Mitocôndrias/metabolismo , Molibdênio/química , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Propriedades de Superfície
10.
ACS Appl Mater Interfaces ; 13(45): 53646-53658, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34748304

RESUMO

Intrinsic tumor microenvironment (TME)-related therapeutic resistance and nontumor-specific imaging have limited the application of imaging-guided cancer therapy. Herein, a TME-responsive MnO2-based nanoplatform coupled with turn-on and always-on fluorescence probes was designed through a facile biomineralization method for imaging-guided photodynamic/chemodynamic/photothermal therapy (PDT/CDT/PTT). After the tumor-targeting delivery of the AuNCs@MnO2-ICG@AS1411 (AMIT) nanoplatform via aptamer AS1411, the TME-responsive dissociation of MnO2 generated sufficient O2 and Mn2+ with the consumption of GSH for improving PDT efficacy and Fenton-like reaction-mediated CDT. Simultaneously, the released small-sized ICG and AuNCs facilitated PDT and PTT efficacy via the deep tumor penetration. Moreover, the turn-on fluorescence of AuNCs revealed the real-time TME-responsive MnO2 degradation process, and the always-on ICG fluorescence enabled the in situ monitoring of the payload distribution in vitro and in vivo. The AMIT NPs also provided magnetic resonance and thermal imaging guidance for the enhanced PDT, CDT, and PTT. Therefore, this all-in-one nanosystem provides a simple and versatile strategy for multiple imaging-guided theranostic applications.


Assuntos
Antineoplásicos/farmacologia , Corantes Fluorescentes/farmacologia , Verde de Indocianina/farmacologia , Imagem Óptica , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Aptâmeros de Nucleotídeos/química , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Ouro/química , Humanos , Verde de Indocianina/síntese química , Verde de Indocianina/química , Células MCF-7 , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Oligodesoxirribonucleotídeos/química , Oxigênio/análise , Oxigênio/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Microambiente Tumoral/efeitos dos fármacos
11.
Molecules ; 26(19)2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34641533

RESUMO

Photodynamic therapy (PDT) represents an effective treatment to cure cancer. The targeting ability of the photosensitizer is of utmost importance. Photosensitizers that discriminate cancer cells can avoid the killing of normal cells and improve PDT efficacy. However, the design and synthesis of photosensitizers conjugated with a recognition unit of cancer cell markers is complex and may not effectively target cancer. Considering that the total RNA content in cancer cells is commonly higher than in normal cells, this study has developed the photosensitizer QICY with RNA-targeting abilities for the discrimination of cancer cells. QICY was specifically located in cancer cells rather than normal cells due to their stronger electrostatic interactions with RNA, thereby further improving the PDT effects on the cancer cells. After intravenous injection into mice bearing a xenograft tumor, QICY accumulated into the tumor location through the enhanced permeability and retention effect, automatically targeted cancer cells under the control of RNA, and inhibited tumor growth under 630 nm laser irradiation without obvious side effects. This intelligent photosensitizer with RNA-targeting ability not only simplifies the design and synthesis of cancer-cell-targeting photosensitizers but also paves the way for the further development of highly efficient PDTs.


Assuntos
Neoplasias/patologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , RNA/química , Animais , Células COS , Linhagem Celular Tumoral , Chlorocebus aethiops , Feminino , Humanos , Injeções Intravenosas , Terapia com Luz de Baixa Intensidade , Células MCF-7 , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/síntese química , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Mater Chem B ; 9(42): 8832-8841, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34636390

RESUMO

Tumor-targeting gold nanorods (AuNRs) assembled through Au-S bonds have been widely used for photothermal therapy (PTT) via intravenous injection. However, with extended in vivo circulation times, biothiols can replace some S-modified targeting ligands on the surface of the AuNRs, which lowers their targeting efficacy towards cancer cells, resulting in a non-ideal PTT effect. To address this problem, herein, we utilized Se-modified AuNRs to establish a dual functional nanoprobe (Casp-RGD-Se-AuNRs) for improving the therapeutic effect and real-time monitoring of Caspase-9 levels to indicate the degree of cell apoptosis. The experiments demonstrated that the Casp-RGD-Se-AuNRs are better at avoiding interference from biothiols than the S-modified nanoprobe (Casp-RGD-S-AuNRs) for extended blood-circulation times after intravenous injection, significantly improving the PTT efficacy via more effectively targeting cancer cells. Simultaneously, the change of Caspase-9 levels visually shows the degree of apoptosis. Moreover, an in vivo study showed that, compared with the S-modified nanoprobe, the Se-modified nanoprobe exhibits a higher delivery efficiency to the tumor region after intravenous injection (accumulation in the tumor increased by 87%) and a better anticancer efficacy under NIR light irradiation (the tumor inhibition rate increased 6-fold). This work provides a valuable strategy to overcome the off-target problem, and new ideas for avoiding interference by biomolecules during blood circulation.


Assuntos
Antineoplásicos/farmacologia , Ouro/farmacologia , Nanotubos/química , Fármacos Fotossensibilizantes/farmacologia , Terapia Fototérmica , Selênio/farmacologia , Compostos de Sulfidrila/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ouro/sangue , Ouro/química , Humanos , Raios Infravermelhos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Selênio/sangue , Selênio/química , Compostos de Sulfidrila/sangue , Compostos de Sulfidrila/química
13.
ACS Appl Mater Interfaces ; 13(39): 46451-46463, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34570459

RESUMO

Light-driven endogenous water oxidation has been considered as an attractive and desirable way to obtain O2 and reactive oxygen species (ROS) in the hypoxic tumor microenvironment. However, the use of a second near-infrared (NIR-II) light to achieve endogenous H2O oxidation to alleviate tumor hypoxia and realize deep hypoxic tumor phototherapy is still a challenge. Herein, novel plasmonic Ag-AgCl@Au core-shell nanomushrooms (NMs) were synthesized by the selective photodeposition of plasmonic Au at the bulge sites of the Ag-AgCl nanocubes (NCs) under visible light irradiation. Upon NIR-II light irradiation, the resulting Ag-AgCl@Au NMs could oxidize endogenous H2O to produce O2 to alleviate tumor hypoxia. Almost synchronously, O2 could react with electrons on the conduction band of the AgCl core to generate superoxide radicals (O2•-)for photodynamic therapy. Moreover, Ag-AgCl@Au NMs with an excellent photothermal performance could further promote the phototherapy effect. In vitro and in vivo experimental results show that the resulting Ag-AgCl@Au NMs could significantly improve tumor hypoxia and enhance phototherapy against a hypoxic tumor. The present study provides a new strategy to design H2O-activatable, O2- and ROS-evolving NIR II light-response nanoagents for the highly efficient and synergistic treatment of deep O2-deprived tumor tissue.


Assuntos
Antineoplásicos/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/síntese química , Antineoplásicos/efeitos da radiação , Catálise , Linhagem Celular Tumoral , Ouro/química , Ouro/efeitos da radiação , Ouro/uso terapêutico , Raios Infravermelhos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/efeitos da radiação , Camundongos Endogâmicos BALB C , Oxigênio/metabolismo , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Terapia Fototérmica , Prata/química , Prata/efeitos da radiação , Prata/uso terapêutico , Compostos de Prata/química , Compostos de Prata/efeitos da radiação , Compostos de Prata/uso terapêutico , Água/química
14.
J Mater Chem B ; 9(33): 6623-6633, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34378616

RESUMO

Cancer treatment has been recently energized by nanomaterials that simultaneously offer diagnostic and therapeutic effects. Among the imaging and treatment modalities in frontline research today, magnetic resonance imaging (MRI) and phototherapy have gained significant interest due to their noninvasiveness among other intriguing benefits. Herein, Fe(iii) was adsorbed on titanium dioxide to develop magnetic Fe-TiO2 nanocomposites (NCs) which leverage the Fe moiety in a double-edge-sword approach to: (i) achieve T1-weighted MRI contrast enhancement, and (ii) improve the well-established photodynamic therapeutic efficacy of TiO2 nanoparticles. Interestingly, the proposed NCs exhibit classic T1 MRI contrast agent properties (r1 = 1.16 mM-1 s-1) that are comparable to those of clinically available contrast agents. Moreover, the NCs induce negligible cytotoxicity in traditional methods and show remarkable support to the proliferation of intestine organoids, an advanced toxicity evaluation system based on three-dimensional organoids, which could benefit their potential safe application for in vivo cancer theranostics. Aided by the Fenton reaction contribution of the Fe component of the Fe-TiO2 NCs, considerable photo-killing of cancer cells is achieved upon UV irradiation at very low (2.5 mW cm-2) intensity in typical cancer PDT. It is therefore expected that this study will guide the engineering of other biocompatible magnetic titania-based nanosystems with multi-faceted properties for biomedical applications.


Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Imageamento por Ressonância Magnética , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Teste de Materiais , Camundongos , Camundongos Endogâmicos C57BL , Nanotubos/química , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Titânio/química , Titânio/farmacologia , Raios Ultravioleta
15.
Macromol Biosci ; 21(12): e2100229, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34390189

RESUMO

The integration of hypoxia-activated chemotherapy with photodynamic therapy (PDT) has newly become a potent strategy for tumor treatment. Herein, a reactive oxygen species (ROS)-responsive drug carriers (PS@AQ4N/mPEG-b-PSe NPs) are fabricated based on the amphiphilic selenium-containing methoxy poly(ethylene glycol)-polycarbonate (mPEG-b-PSe), the hydrophobic photosensitizer (PS), and hypoxia-activated prodrug Banoxantrone (AQ4N). The obtained nanoparticles are spherical with an average diameter of 100 nm as characterized by transmission electron microscope (TEM) and dynamic laser scattering (DLS) respectively. The encapsulation efficiency of the PS and AQ4N reaches 92.83% and 51.04% at different conditions, respectively, by UV-vis spectrophotometer. It is found that the drug release is accelerated due to the good ROS responsiveness of mPEG-b-PSe and the cumulative release of AQ4N is up to 89% within 30 h. The cell test demonstrates that the nanoparticles dissociate when triggered by the ROS stimuli in the cancer cells, thus the PS is exposed to more oxygen and the ROS generation efficiency is enhanced accordingly. The consumption of oxygen during PDT leads to the increased tumor hypoxia, and subsequently activates AQ4N into cytotoxic counterpart to inhibit tumor growth. Therefore, the synergistic therapeutic efficacy demonstrates this drug delivery has great potential for antitumor therapy.


Assuntos
Portadores de Fármacos , Nanopartículas , Fotoquimioterapia , Fármacos Fotossensibilizantes , Pró-Fármacos , Espécies Reativas de Oxigênio/metabolismo , Selênio , Linhagem Celular Tumoral , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacocinética , Fármacos Fotossensibilizantes/farmacologia , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Pró-Fármacos/farmacologia , Selênio/química , Selênio/farmacocinética , Selênio/farmacologia
16.
J Mater Chem B ; 9(29): 5785-5793, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34190308

RESUMO

Dual phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) is considered to be a more effective therapeutic method against cancer than single treatment. Therefore, the development of a single material with both near-infrared (NIR)-laser-triggered PDT and PTT abilities is highly desirable but remains a great challenge. A design philosophy for photosensitizers for integrated PDT and PTT treatment has been put forward: (1) a high molar extinction coefficient in the NIR region; (2) suitable LUMO and T1 energy levels to regulate intersystem crossing for effective singlet oxygen (1O2) generation for PDT; and (3) the suppression of fluorescence emission to enhance the process of nonradiative transition with appropriate chemical modifications. Herein, an "all-in-one" functional material, di-cyan substituted 5,12-dibutylquinacridone (DCN-4CQA), for diagnosis and therapy was obtained. DCN-4CQA possesses dual-functional phototherapeutic activity and NIR fluorescence and it was produced via a facile synthesis process from the classic organic photoelectric material quinacridone. We then prepared smart water-soluble nanoparticles (NPs), DCN-4CQA/F127, using Pluronic® 127 (F127) as a drug carrier. The NPs exhibited excellent biocompatibility, robust photostability, NIR fluorescence, a high photothermal conversion efficiency (η = 47.3%), and sufficient 1O2 generation (ΦΔ = 24.3%) under NIR laser irradiation. Remarkably, the DCN-4CQA/F127 NPs significantly inhibited tumor growth in mice subjected to NIR laser irradiation. This study provides a new route for the development of highly efficient, low-cytotoxicity photosensitizers for fluorescence-imaging-guided PTT/PDT.


Assuntos
Antineoplásicos/farmacologia , Corantes Fluorescentes/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Imagem Óptica , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/química , Células HeLa , Compostos Heterocíclicos de 4 ou mais Anéis/química , Humanos , Raios Infravermelhos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/patologia , Camundongos , Estrutura Molecular , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química
17.
J Mater Chem B ; 9(25): 5069-5075, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34137418

RESUMO

Chemodynamic therapy (CDT) is an emerging approach to overcome bacterial infections that can efficiently convert hydrogen peroxide (H2O2) to generate highly toxic hydroxyl radicals (˙OH). How to develop safe and effective CDT-based strategies is in high demand but challenging. Herein, a cascade catalytic nanoplatform (GOx-NCs/Fe3O4) was designed by absorbing glucose oxidase (GOx) onto the surface of covalent-assembled polymer capsules (NCs) encapsulating Fe3O4 nanoparticles. With the presence of glucose, GOx could effectively catalyze it to produce H2O2 and result in a decrease in pH value, both of which would assist the subsequent Fenton reaction. Encapsulated Fe3O4 nanoparticles would subsequently trigger H2O2 to produce ˙OH, which could make antibacterial CDT come true. More importantly, the polymer capsules exhibited little to no cytotoxicity towards mammalian cells, which might provide more opportunities and potential to apply in other fields.


Assuntos
Antibacterianos/farmacologia , Calixarenos/farmacologia , Escherichia coli/efeitos dos fármacos , Nanopartículas de Magnetita/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Calixarenos/síntese química , Calixarenos/química , Catálise , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células NIH 3T3 , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química
19.
J Fluoresc ; 31(2): 551-557, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33464456

RESUMO

GQDs decorated with europium (Eu), silver (Ag) and selenium (Se) at molar ratios of 0.1%, 0.3% and 0.5% were produced for the first time at different temperatures of 180 °C, 200 °C and 220 °C. Surface passivation was carried out with polyethylene glycol (PEG) to increase the intensity of photoluminescence (PL) of the produced samples. The prepared quantum dots were characterized by X-Ray diffraction (XRD), Fourier transformed infrared spectroscopy (FTIR), transmission electron microscopy (TEM), PL and ultraviolet-visible spectroscopy. GQDs synthesized at 180 °C and decorated with Se (0.3%) had maximum PL intensity along with long lasted afterglow over 90 min compared with other samples. Excitation wavelength at 360 nm produced maximum emission at 600-900 nm and resulted in high singlet oxygen (1O 2) generation which makes it a good candidate for photodynamic therapy applications.


Assuntos
Grafite/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Pontos Quânticos/química , Európio/química , Fármacos Fotossensibilizantes/síntese química , Espécies Reativas de Oxigênio/análise , Selênio/química , Prata/química
20.
J Mater Chem B ; 9(4): 1018-1029, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33432955

RESUMO

Recently, phototherapy has attracted much attention due to its negligible invasiveness, insignificant toxicity and excellent applicability. The construction of a newly proposed nanosystem with synergistic photothermal and photodynamic tumor-eliminating properties requires a delicate structure design. In this work, a novel therapeutic nanoplatform (denoted as BCS-Ce6) based on defective cobalt hydroxide nanosheets was developed, which realized hypoxia-relieved photothermal-enhanced photodynamic therapy against cancer. Defective cobalt hydroxide exhibited high photothermal conversion efficacy at the near-infrared region (49.49% at 808 nm) as well as enhanced catalase-like activity to produce oxygen and greatly boost the singlet oxygen generation by a photosensitizer, Ce6, realizing efficacious dual-modal phototherapy. In vivo and in vitro experiments revealed that BCS-Ce6 can almost completely extinguish implanted tumors in a mouse model and present satisfactory biocompatibility during the treatment. This work sets a new angle of preparing photothermal agents and constructing comprehensive therapeutic nanosystems with the ability to modulate the hypoxic tumor microenvironment for efficient cancer therapy.


Assuntos
Antineoplásicos/farmacologia , Hipóxia Celular/efeitos dos fármacos , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células Hep G2 , Humanos , Hidróxidos/química , Hidróxidos/farmacologia , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas Experimentais/metabolismo , Neoplasias Hepáticas Experimentais/patologia , Camundongos , Camundongos Endogâmicos ICR , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Dióxido de Silício/química , Dióxido de Silício/farmacologia , Propriedades de Superfície , Tiazóis/química , Tiazóis/farmacologia , Elementos de Transição/química , Elementos de Transição/farmacologia , Células Tumorais Cultivadas
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