Specific disruption of glutathione-defense system with activatable single molecule-assembled nanoprodrug for boosted photodynamic/chemotherapy eradication of drug-resistant tumors.
Biomaterials
; 290: 121867, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-36326511
ABSTRACT
Developing single molecule-assembled nanoprodrugs that can reverse the glutathione (GSH)-mediated drug resistance of tumors provides promising potentials for precision and effective cancer theranostics. Herein, we developed a novel single molecule-assembled nanoprodrug for effective photodynamic/chemotherapeutic eradication of drug-resistant tumors via the multistage GSH-depletion. The nanoprodrug MSSP-NP could be fancily fabricated by self-assembly of an amphiphilic activatable molecular MSSP, which is synthesized by covalently conjugating the photosensitizer methylene blue (MB) with a GSH-sensitive cisplatin prodrug via a tumor targeting thiolated polypeptide. Upon the nanoprodrug MSSP-NP systematic administrated, its photoactivities and pharmacological effects can be thoroughly switched on by intracellular GSH to produce the photosensitizer MB and chemotherapeutic drug cisplatin, along with the multi-step consumption of GSH, which could remarkably boost oxidative stress and reverse the drug resistance. As a result, the nanoprodrug could effectively disrupt the tumor GSH-defense system to afford high-efficiency photodynamic/chemotherapeutic inhibition of drug resistance tumors (96.4%) with minimum side effects.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
/
Pró-Fármacos
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Nanopartículas
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Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article