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Abstract Title:

Gold Nanorods Exhibit Intrinsic Therapeutic Activity via Controlling6-Methyladenosine-Based Epitranscriptomics in Acute Myeloid Leukemia.

Abstract Source:

ACS Nano. 2021 Oct 25. Epub 2021 Oct 25. PMID: 34694795

Abstract Author(s):

Yangyang Du, Mingda Han, Kunxia Cao, Qing Li, Jiuxia Pang, Liping Dou, Shujun Liu, Zhan Shi, Fei Yan, Shouhua Feng

Article Affiliation:

Yangyang Du

Abstract:

Reprograming the6-methyladenosine (mA) landscape is a promising therapeutic strategy against recalcitrant leukemia. In this study, we synthesized gold nanorods (GNRs) of different aspect ratios using a binary surfactant mixture of hexadecyltrimethylammonium bromide and sodium oleate. Following surface functionalization with chitosan and a 12-mer peptide, GNRa-CSP12 measuring 130× 21 nmwas selectively taken up by leukemia cells via targeted endocytosis. Low doses of GNRa-CSP12 inhibited the growth of leukemia cells by disrupting the redox balance and inducing ferroptosis. Mechanistically, GNRa-CSP12 abrogated endogenous Fe-dependent mA demethylase activity, which led to global mA hypomethylation and post-transcriptional regulation of downstream genes that are involved in glycolysis, hypoxia, and immune checkpoint pathways. In addition, combination treatment with GNRa-CSP12 and tyrosine kinases inhibitors (TKIs) synergistically obviated the mA-mediated TKI resistance phenotype. Finally, GNRa-CSP12 as a potential immunotherapeutic agent could enhance immunotherapy outcome in leukemia. Our preclinical findings provide the proof-of-concept for targeting mA-methylation-based epitranscriptomics using nanoparticle as an "epigenetic drug" for cancer therapy.

Study Type : In Vitro Study

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