Orally deliverable biomimetic nucleic acid therapies for targeted treatment of atherosclerosis.
10.1016/j.apsb.2025.07.039
- Author:
Chenwen LI
1
;
Yidan CHEN
1
;
Yuan LI
2
;
Huan LIU
1
;
Shengqian YANG
1
;
Yongyao LIN
1
;
Yuantong QI
1
;
Songling HAN
3
;
Yin DOU
1
;
Gaoxing LUO
3
;
Yingxue HAO
4
;
Jianxiang ZHANG
1
Author Information
1. Department of Pharmaceutics, College of Pharmacy, Third Military Medical University (Army Medical University), Chongqing 400038, China.
2. Department of Neurology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
3. State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University (Army Medical University), Chongqing 400038, China.
4. Department of Vascular Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
- Publication Type:Journal Article
- Keywords:
Atherosclerosis;
Cholesterol efflux;
Lymphatic transport;
Microcapsule;
Nucleic acid;
Oral delivery;
Targeted therapy;
microRNA-33
- From:
Acta Pharmaceutica Sinica B
2025;15(11):6052-6069
- CountryChina
- Language:English
-
Abstract:
Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE -/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.
