GSH-responsive SN38 dimer-loaded shape-transformable nanoparticles with iRGD for enhancing chemo-photodynamic therapy.
Acta Pharm Sin B
; 10(12): 2348-2361, 2020 Dec.
Article
en En
| MEDLINE
| ID: mdl-33354506
ABSTRACT
Accurate tumor targeting, deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine. To achieve these requirements, a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer (d-SN38)-loaded nanoparticles (d-SN38@NPs/iRGD). Upon intravenous injection, d-SN38@NPs with high drug loading efficiency (33.92 ± 1.33%) could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD. The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy. The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm, which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor. In vitro, co-administering iRGD with d-SN38@NPs+laser showed higher cellular uptake, apoptosis ratio and multicellular spheroid penetration. In vivo, d-SN38@NPs/iRGD+laser displayed advanced penetration and accumulation in tumor, leading to 60.89% of tumor suppression in 4T1 tumor-bearing mouse model with a favorable toxicity profile. Our new strategy combining iRGD with structural transformable nanoparticles greatly improves tumor targeting, penetrating and retention, and empowers anticancer efficacy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Acta Pharm Sin B
Año:
2020
Tipo del documento:
Article
País de afiliación:
China