Self-Illuminating Triggered Release of Therapeutics from Photocleavable Nanoprodrug for the Targeted Treatment of Breast Cancer.
ACS Appl Mater Interfaces
; 14(7): 8766-8781, 2022 Feb 23.
Article
em En
| MEDLINE
| ID: mdl-35166116
ABSTRACT
Photocleavable biomaterials and bioconjugates have been widely researched for tissue engineering, cell culture, and therapeutics delivery. However, most in vivo applications of these materials or conjugates require external irradiation, and some of the light sources used such as ultraviolet (UV) light have poor tissue penetration. To address these key limitations, we synthesized a photocleavable nanoprodrug using luminol (a luminescent donor), chlorambucil (CHL, i.e., an antitumor drug with a photocleavable linker), and polyethylene glycol-folic acid conjugates (a targeted moiety) loaded onto polyamidoamine (PAMAM). The synthesized nanoprodrug can smartly release its payloads through photocleavage of photoresponsive linker by UV light, which was produced in situ by reacting luminol with pathological reactive oxygen species (ROS). The luminescence performance and absorption spectrum of this nanoprodrug was characterized in detail. In vitro cellular assays verified that the nanoprodrugs could be efficiently internalized by 4T1 and MDA-MB-231 cells, and the CHL released from the nanoprodrugs could distinctly decrease cell viability through the damage of DNA in cells. In vivo animal experiments demonstrated that the nanoprodrugs were mainly accumulated at tumor sites, and the antitumor drug CHL could be smartly released from the nanoprodrugs through cleavage of photosensitive linkers at a high level of ROS. The released CHL significantly inhibited the growth of tumors without any obvious adverse effects. Our results provide a practicable strategy to expand the in vivo application of photocleavable biomaterials and bioconjugates.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article