Multi-Targeted Peptide-Modified Gold Nanoclusters for Treating Solid Tumors in the Liver

Xiao, Feng1; Chen, Yao1; Qi, Jie1; Yao, Qiaofeng2; Xie, Jianping2; Jiang, Xingyu1

2023-03-01

10.1002/adma.202210412

ADVANCED MATERIALS   Impact Factor & Quartile

0935-9648

1521-4095

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.

apoptosis autophagy endoplasmic reticulum stress gold nanoclusters liver cancer

SCI

English

First ; Corresponding

National Key R&D Program of China["2018YFA0902600","2020YFA0908900","2021YFF1200800","2021YFF1200103","2022YFB3804"] ; National Natural Science Foundation of China[22234004] ; Guangdong Provincial Key Laboratory of Advanced Biomaterials[2022B1212010003] ; Shenzhen Science and Technology Program[KQTD20190929172743294] ; Shenzhen Key Laboratory of Smart Healthcare Engineering[ZDSYS20200811144003009]

Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics

Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter

WOS:000961643500001

WILEY-V C H VERLAG GMBH

MATERIALS SCIENCE

Web of Science

1.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen Key Lab Smart Healthcare Engn, Guangdong Prov Key Lab Adv Biomat, Shenzhen 518055, Guangdong, Peoples R China
2.Natl Univ Singapore, Dept Chem & Biomol Engn, Kent Ridge, Singapore 117585, Singapore

Xiao, Feng,Chen, Yao,Qi, Jie,et al. Multi-Targeted Peptide-Modified Gold Nanoclusters for Treating Solid Tumors in the Liver[J]. ADVANCED MATERIALS,2023.

Xiao, Feng,Chen, Yao,Qi, Jie,Yao, Qiaofeng,Xie, Jianping,&Jiang, Xingyu.(2023).Multi-Targeted Peptide-Modified Gold Nanoclusters for Treating Solid Tumors in the Liver.ADVANCED MATERIALS.

Xiao, Feng,et al."Multi-Targeted Peptide-Modified Gold Nanoclusters for Treating Solid Tumors in the Liver".ADVANCED MATERIALS (2023).