Ce6/PTX2-NP/G@NHs Confer Radiosensitivity in Non-Small Cell Lung Cancer via Promotion of Apoptotic Body-Mediated Neighboring Effects.
ACS Biomater Sci Eng
; 9(5): 2793-2805, 2023 05 08.
Article
em En
| MEDLINE
| ID: mdl-37066871
ABSTRACT
This study fabricates a nanoparticle delivery system of gold nanoparticles-dextran nanoparticles loaded with hypoxia-activated paclitaxel dimeric prodrug nanoparticles (PTX2-NP) and photosensitizer chlorin e6/paclitaxel-nanoparticle/gold@N-(2-hydroxypropyl) (Ce6/PTX2-NP/G@NHs) and analyzed the possible molecular mechanism for enhancing the radiosensitivity of non-small cell lung cancer (NSCLC). Ce6/PTX2-NP/G@NHs were prepared by a coupling reaction and dextran inclusion, followed by characterization using spectroscopy techniques. The cellular uptake and cytotoxicity of Ce6/PTX2-NP/G@NHs were analyzed. Radiosensitizing effects of the nanoparticles were evaluated by determining the malignant phenotypes and reactive oxygen species production of A549 cells and PI3K/AKT pathway-related proteins under 685 nm laser irradiation. A549 tumor-bearing nude mice were modeled to further confirm the radiosensitizing effect. Ce6/PTX2-NP/G@NHs were effectively internalized by A549 cells, producing cytotoxicity under laser irradiation. Ce6/PTX2-NP/G@NHs reduced cell viability, clonogenic potential, migration, and invasion along with reactive oxygen species (ROS) production while promoting apoptosis in A549 cells under laser irradiation. By inhibiting the PI3K/AKT pathway, Ce6/PTX2-NP/G@NHs increased the sensitivity of A549 cells to radiotherapy where apoptotic body (ApoBD)-mediated neighboring effects also played a key role. Ce6/PTX2-NP/G@NHs accumulated in tumor sites of nude mice and enhanced the radiosensitivity of NSCLC. Ce6/PTX2-NP/G@NHs showed no obvious toxicity or side effects in vivo. Collectively, the new Ce6/PTX2-NP/G@NHs nanoparticle delivery system can enhance the radiosensitivity of NSCLC via the promotion of ApoBD-mediated neighboring effects and inactivation of the PI3K/AKT pathway.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
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Radiossensibilizantes
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Carcinoma Pulmonar de Células não Pequenas
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Nanopartículas Metálicas
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Vesículas Extracelulares
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Neoplasias Pulmonares
Limite:
Animals
Idioma:
En
Revista:
ACS Biomater Sci Eng
Ano de publicação:
2023
Tipo de documento:
Article