Disrupting glycolysis and DNA repair in anaplastic thyroid cancer with nucleus-targeting platinum nanoclusters.
J Control Release
; 369: 517-530, 2024 May.
Article
in En
| MEDLINE
| ID: mdl-38569942
ABSTRACT
Cancer cells rely on aerobic glycolysis and DNA repair signals to drive tumor growth and develop drug resistance. Yet, fine-tuning aerobic glycolysis with the assist of nanotechnology, for example, dampening lactate dehydrogenase (LDH) for cancer cell metabolic reprograming remains to be investigated. Here we focus on anaplastic thyroid cancer (ATC) as an extremely malignant cancer with the high expression of LDH, and develop a pH-responsive and nucleus-targeting platinum nanocluster (Pt@TAT/sPEG) to simultaneously targets LDH and exacerbates DNA damage. Pt@TAT/sPEG effectively disrupts LDH activity, reducing lactate production and ATP levels, and meanwhile induces ROS production, DNA damage, and apoptosis in ATC tumor cells. We found Pt@TAT/sPEG also blocks nucleotide excision repair pathway and achieves effective tumor cell killing. In an orthotopic ATC xenograft model, Pt@TAT/sPEG demonstrates superior tumor growth suppression compared to Pt@sPEG and cisplatin. This nanostrategy offers a feasible approach to simultaneously inhibit glycolysis and DNA repair for metabolic reprogramming and enhanced tumor chemotherapy.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Platinum
/
Thyroid Neoplasms
/
DNA Repair
/
Thyroid Carcinoma, Anaplastic
/
Glycolysis
/
Mice, Nude
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Language:
En
Journal:
J Control Release
Journal subject:
FARMACOLOGIA
Year:
2024
Document type:
Article