Novel, Self-Distinguished, Dual Stimulus-Responsive Therapeutic Nanoplatform for Intracellular On-Demand Drug Release.
Mol Pharm
; 17(7): 2435-2450, 2020 07 06.
Article
en En
| MEDLINE
| ID: mdl-32459486
ABSTRACT
On-demand drug release nanoplatforms are promising alternative strategies for enhancing the therapeutic effect of cancer chemotherapy. However, these nanoplatforms still have many drawbacks including rapid blood clearance, nontargeted specificity, and a lack of immune escape function. Even worse, they are also hindered via the dosage-limiting toxicity of traditional chemotherapeutic drugs. Herein, both dual-functional mannose (enhances the antitumor activity of chemotherapeutic drugs and exhibits an innate affinity against the lectin receptor) and amphiphilic d-α-tocopheryl polyethylene glycol 1000 succinate were selected to be covalently linked via a redox-responsive monothioether linkage. The synthesized self-distinguished polymer (TSM), as a structural motif, can be self-assembled into nanoparticles (TSM NPs) in an aqueous solution, in which doxorubicin (DOX) is loaded by weak interactions (TSM-DOX NPs). These TSM-DOX NPs can provide targeted, on-demand drug release under dual stimuli from lysosomal acidity and glutathione (GSH). In addition, TSM-DOX NPs can be self-distinguished via tumor cells in vitro and specifically self-distinguished from the tumor site in vivo. Further in vitro and in vivo research consistently demonstrated that TSM-DOX NPs display highly synergistic chemotherapeutic effects. Taken together, the data show that the self-distinguished GSH-responsive polymer TSM has the potential to load various therapeutic agents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polímeros
/
Portadores de Fármacos
/
Doxorrubicina
/
Nanopartículas
/
Liberación de Fármacos
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Antibióticos Antineoplásicos
/
Neoplasias
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Mol Pharm
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACIA
/
FARMACOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China