Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 7 de 7
Filtrar
Más filtros

Bases de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
ACS Cent Sci ; 9(8): 1679-1691, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37637741

RESUMEN

The development of highly effective photosensitizers (PSs) for photodynamic therapy remains a great challenge at present. Most PSs rely on the heavy-atom effect or the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) effect to promote ISC, which brings about additional cytotoxicity, and the latter is susceptible to the interference of solvent environment. Herein, an immanent universal property named photoinduced molecular vibrational torsion (PVT)-enhanced spin-orbit coupling (PVT-SOC) in PSs has been first revealed. PVT is verified to be a widespread intrinsic property of quinoid cyanine (QCy) dyes that occurs on an extremely short time scale (10-10 s) and can be captured by transient spectra. The PVT property can provide reinforced SOC as the occurrence of ISC predicted by the El Sayed rules (1ππ*-3nπ*), which ensures efficient photosensitization ability for QCy dyes. Hence, QTCy7-Ac exhibited the highest singlet oxygen yield (13-fold higher than that of TCy7) and lossless fluorescence quantum yield (ΦF) under near-infrared (NIR) irradiation. The preeminent photochemical properties accompanied by high biosecurity enable it to effectively perform photoablation in solid tumors. The revelation of this property supplies a new route for constructing high-performance PSs for achieving enhanced cancer phototherapy.

2.
Adv Healthc Mater ; 12(27): e2301091, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37321560

RESUMEN

Photothermal therapy (PTT) is a promising approach to cancer treatment. Heptamethine cyanine (Cy7) is an attractive photothermal reagent because of its large molar absorption coefficient, good biocompatibility, and absorption of near-infrared irradiation. However, the photothermal conversion efficiency (PCE) of Cy7 is limited without ingenious excitation-state regulation. In this study, the photothermal conversion ability of Cy7 is efficiently enhanced based on photo-induced electron transfer (PET)-triggered structural deformation. Three Cy7 derivatives, whose Cl is replaced by carbazole, phenoxazine, and phenothiazine at the meso-position (CZ-Cy7, PXZ-Cy7, and PTZ-Cy7), are presented as examples to demonstrate the regulation of the energy release of the excited states. Because the phenothiazine moiety exhibits an obvious PET-induced structural deformation in the excited state, which quenches the fluorescence and inhibits intersystem crossing of S1 →T1 , PTZ-Cy7 exhibits a PCE as high as 77.5%. As a control, only PET occurs in PXZ-Cy7, with a PCE of 43.5%. Furthermore, the PCE of CZ-Cy7 is only 13.0% because there is no PET process. Interestingly, PTZ-Cy7 self-assembles into homogeneous nanoparticles exhibiting passive tumor-targeting properties. This study provides a new strategy for excited-state regulation for photoacoustic imaging-guided PTT with high efficiency.


Asunto(s)
Nanopartículas , Neoplasias , Técnicas Fotoacústicas , Humanos , Electrones , Fototerapia , Nanopartículas/química , Neoplasias/terapia , Fenotiazinas
3.
Biomaterials ; 296: 122089, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36898223

RESUMEN

Cancer immunotherapy, despite its enormous application prospect, is trapped in the abnormal lactic acid metabolism of tumor cells that usually causes an immunosuppressive tumor microenvironment (ITM). Inducing immunogenic cell death (ICD) not only sensitizes cancer cells to carcer immunity, but also leads to a great increase in tumor-specific antigens. It improves tumor condition from "immune-cold" to "immune-hot". Herein, a near-infrared photothermal agent NR840 was developed and encapsulated into tumor-targeted polymer DSPE-PEG-cRGD and carried lactate oxidase (LOX) by electrostatic interaction, forming self-assembling "nano-dot" PLNR840 with high loading capacity for synergistic antitumor photo-immunotherapy. In this strategy, PLNR840 was swallowed by cancer cells, then dye NR840 was excited at 808 nm to generate heat inducing tumor cell necrosis, which further caused ICD. LOX could serve as a catalyst, reducing lactic acid efflux via regulation of cell metabolism. More importantly, the consumption of intratumoral lactic acid could substantially reverse ITM, including promoting the polarization of tumor-associated macrophages from M2 to M1 type, inhibiting the viability of regulatory T cells for sensitizing photothermal therapy (PTT). After the combination of αPD-L1 (programmed cell death protein ligand 1), PLNR840 restored CD8+ T-cell activity that thoroughly cleaned the pulmonary metastasis of breast cancer in 4T1 mouse model and cured hepatocellular carcinoma in Hepa1-6 mouse model. This study provided an effective PTT strategy to boost "immune-hot" and reprogrammed tumor metabolism for antitumor immunotherapy.


Asunto(s)
Neoplasias , Fototerapia , Animales , Ratones , Fototerapia/métodos , Línea Celular Tumoral , Inmunoterapia/métodos , Polímeros , Terapia Combinada , Antígenos de Neoplasias , Microambiente Tumoral , Neoplasias/terapia
4.
Adv Healthc Mater ; 11(3): e2101449, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34879433

RESUMEN

The principle of photochemical transformation has shown significant inspiration on phototherapy of solid tumors. However, both photodynamic therapy (PDT) and photothermal therapy (PTT) can induce stress response of tumor cells, which draw the attention in recent. Herein, an asymmetric and lollipop like nanostructure consisting of gold nanorod/titanium dioxide (l-TiO2 -GNR) is developed by controlling single head growth of titanium dioxide (TiO2 ) on gold nanorods (GNR). Through the reasonable utilization of hot electrons of GNR by 808 nm light irradiation, l-TiO2 -GNR perform type I-PDT, mild PTT (48 °C), and H2 therapy which is efficient for hypoxic tumors. In particular, H2 can downregulate both triphosadenine and heat shock protein which are found to be main source of tumor stress response. l-TiO2 -GNR opens a new window for treatment of hypoxic tumor by the perfect synergy of type I-PDT, mild PTT, and H2 therapy.


Asunto(s)
Nanotubos , Fotoquimioterapia , Oro/química , Oro/farmacología , Nanotubos/química , Fototerapia , Terapia Fototérmica
5.
Chem Sci ; 12(41): 13809-13816, 2021 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-34760166

RESUMEN

Highly efficient triplet photosensitizers (PSs) have attracted increasing attention in cancer photodynamic therapy where photo-induced reactive oxygen species (ROSs, such as singlet oxygen) are produced via singlet-triplet intersystem crossing (ISC) of the excited photosensitizer to kill cancer cells. However, most PSs exhibit the fatal defect of a generally less-than-1% efficiency of ISC and low yield of ROSs, and this defect strongly impedes their clinical application. In the current work, a new strategy to enhance the ISC and high phototherapy efficiency has been developed, based on the molecular design of a thio-pentamethine cyanine dye (TCy5) as a photosensitizer. The introduction of an electron-withdrawing group at the meso-position of TCy5 could dramatically reduce the singlet-triplet energy gap (ΔE st) value (from 0.63 eV to as low as 0.14 eV), speed up the ISC process (τ ISC = 1.7 ps), prolong the lifetime of the triplet state (τ T = 319 µs) and improve singlet oxygen (1O2) quantum yield to as high as 99%, a value much higher than those of most reported triplet PSs. Further in vitro and in vivo experiments have shown that TCy5-CHO, with its efficient 1O2 generation and good biocompatibility, causes an intense tumor ablation in mice. This provides a new strategy for designing ideal PSs for cancer photo-therapy.

6.
Chem Sci ; 12(31): 10522-10531, 2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34447545

RESUMEN

In recent years, the use of aggregation-induced emission luminogens (AIEgens) for biological imaging and phototherapy has become an area of intense research. However, most traditional AIEgens suffer from undesired aggregation in aqueous media with "always on" fluorescence, or their targeting effects cannot be maintained accurately in live cells with the microenvironment changes. These drawbacks seriously impede their application in the fields of bio-imaging and antitumor therapy, which require a high signal-to-noise ratio. Herein, we propose a molecular design strategy to tune the dispersity of AIEgens in both lipophilic and hydrophilic systems to obtain the novel near-infrared (NIR, ∼737 nm) amphiphilic AIE photosensitizer (named TPA-S-TPP) with two positive charges as well as a triplet lifetime of 11.43 µs. The synergistic effects of lipophilicity, electrostatic interaction, and structure-anchoring enable the wider dynamic range of AIEgen TPA-S-TPP for mitochondrial targeting with tolerance to the changes of mitochondrial membrane potential (ΔΨ m). Intriguingly, TPA-S-TPP was difficult for normal cells to be taken up, indicative of low inherent toxicity for normal cells and tissues. Deeper insight into the changes of mitochondrial membrane potential and cleaved caspase 3 levels further revealed the mechanism of tumor cell apoptosis activated by AIEgen TPA-S-TPP under light irradiation. With its advantages of low dark toxicity and good biocompatibility, acting as an efficient theranostic agent, TPA-S-TPP was successfully applied to kill cancer cells and to efficiently inhibit tumor growth in mice. This study will provide a new avenue for researchers to design more ideal amphiphilic AIE photosensitizers with NIR fluorescence.

7.
J Am Chem Soc ; 142(3): 1510-1517, 2020 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-31880443

RESUMEN

It remains a considerable challenge to realize complete tumor suppression and avoid tumor regrowth by rational design of photosensitizers (PSs) to improve their photon utilization. In this Article, we provide a molecular design (Icy-NBF) based on the oxygen-content-regulated deactivation process of excited states. In the presence of overexpressed nitroreductase in hypoxic cancer cells, Icy-NBF is reduced and converted into a molecule with the same skeleton (Icy-NH2), in which the deactivation of the PS under 808 nm light irradiation proceeds via a different pathway: the excited states deactivation pathway of Icy-NBF involves radiative transition and energy transfer between Icy-NBF and O2; as for Icy-NH2, the deactivation pathway is attributed to non-radiative relaxation. By varying the O2 concentration in tumor cells, the therapeutic mechanism of Icy-NBF under 808 nm light irradiation can be switched between photodynamic and photothermal therapies, which maximizes the advantages of phototherapies with no tumor regrowth. Our study provides help in designing of smart PSs with improvement of photon utilization for efficient tumor photoablation.


Asunto(s)
Oxígeno/química , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Terapia Fototérmica/métodos , Línea Celular Tumoral , Humanos , Cinética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA