Journal
ADVANCED MATERIALS
Volume 35, Issue 20, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202210412
Keywords
apoptosis; autophagy; endoplasmic reticulum stress; gold nanoclusters; liver cancer
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In this study, a modified nanoparticle aggregate (AP(1)P(2)-PEG NCs) was designed for the treatment of unresectable solid liver tumors. The findings suggest that the nanoparticle aggregate can achieve the mutual promotion of autophagy and apoptosis in liver tumor cells, leading to a better anti-tumor effect.
Apoptosis and autophagy determine the fate of cancer cells. However, simply promoting apoptosis of tumor cells is limited in the treatment of unresectable solid liver tumors. Generally, autophagy is considered the anti-apoptotic guardian. But the pro-apoptotic effects of autophagy can be activated by excessive endoplasmic reticulum (ER) stress. Here, amphiphilic peptide-modified glutathione (GSH)-gold nanocluster aggregates (AP(1)P(2)-PEG NCs) were designed with the enrichment of solid liver tumors and the prolonged stress in the ER, which can achieve the mutual promotion of autophagy and apoptosis in liver tumor cells. In this study, orthotopic and subcutaneous liver tumor models show the anti-tumor effectiveness of AP(1)P(2)-PEG NCs, with a better antitumor effect than sorafenib, biosafety (Lethal Dose, 50% (LD50) of 827.3 mg kg(-1)), wide therapeutic window (non-toxic in 20 times of therapeutic concentration) and high stability (blood half-life of 4 h). These findings identify an effective strategy to develop peptide-modified gold nanocluster aggregates with low toxicity, high potency, and selectivity for solid liver tumors treatment.
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