Polyglutamine-Specific Gold Nanoparticle Complex Alleviates Mutant Huntingtin-Induced Toxicity

Devi Wahyuningtyas, Wen Hao Chen, Ruei Yu He, Yung An Huang, Chia Kang Tsao, Yu Jung He, Chu Yi Yu, Po Chao Lu, Yu Cai Chen, Sheng Hann Wang, Ka Chon Ng, Bryan Po-Wen Chen, Pei Kuen Wei, Jiun Jie Shie, Chun Hong Kuo, Y. Henry Sun, Joseph Jen-Tse Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Huntington's disease (HD) belongs to protein misfolding disorders associated with polyglutamine (polyQ)-rich mutant huntingtin (mHtt) protein inclusions. Currently, it is indicated that the aggregation of polyQ-rich mHtt participates in neuronal toxicity and dysfunction. Here, we designed and synthesized a polyglutamine-specific gold nanoparticle (AuNP) complex, which specifically targeted mHtt and alleviated its toxicity. The polyglutamine-specific AuNPs were prepared by decorating the surface of AuNPs with an amphiphilic peptide (JLD1) consisting of both polyglutamine-binding sequences and negatively charged sequences. By applying the polyQ aggregation model system, we demonstrated that AuNPs-JLD1 dissociated the fibrillary aggregates from the polyQ peptide and reduced its β-sheet content in a concentration-dependent manner. By further integrating polyethyleneimine (PEI) onto AuNPs-JLD1, we generated a complex (AuNPs-JLD1-PEI). We showed that this complex could penetrate cells, bind to cytosolic mHtt proteins, dissociate mHtt inclusions, reduce mHtt oligomers, and ameliorate mHtt-induced toxicity. AuNPs-JLD1-PEI was also able to be transported to the brain and improved the functional deterioration in the HD Drosophila larva model. Our results revealed the feasibility of combining AuNPs, JLD1s, and cell-penetrating polymers against mHtt protein aggregation and oligomerization, which hinted on the early therapeutic strategies against HD.

Original languageEnglish
Pages (from-to)60894-60906
Number of pages13
JournalACS Applied Materials and Interfaces
Issue number51
StatePublished - 29 Dec 2021


  • amyloid
  • gold nanoparticle
  • Huntington's disease
  • peptide
  • polyglutamine


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