Combination of anti-inflammatory therapy and RNA interference by light-inducible hybrid nanomedicine for osteoarthritis treatment.
10.1016/j.apsb.2024.06.009
- Author:
Li QIAO
1
;
Zhiyao LI
2
;
Bowen LI
2
;
Fu ZHANG
2
;
Zhuo YAO
2
;
Chongzhi WU
2
;
Honglin TANG
1
;
Qi PAN
2
;
Peihua SHI
1
;
Yuan PING
1
Author Information
1. Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China.
2. College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
- Publication Type:Journal Article
- Keywords:
Combinational therapy;
Diacerein;
Gold nanocages;
Osteoarthritis;
Pain relief;
Phase-change material;
Photothermal effect;
Poly(β-amino-ester)
- From:
Acta Pharmaceutica Sinica B
2024;14(11):5008-5025
- CountryChina
- Language:English
-
Abstract:
Osteoarthritis (OA) is a type of highly prevalent heterogeneous degenerative disease that leads to joint pain, deformity, the destruction of articular cartilage, and eventual disability. The current treatment strategies for OA often suffer from systemic side effects, poor anti-inflammatory efficacy, and persistent pain. To address these issues, we develop light-inducible nanomedicine that enables the co-delivery of anti-inflammatory drug (diacerein, DIA) and small interfering RNA (siRNA) targeting nerve growth factor (NGF) for pain relief to enhance the therapeutic efficacy of OA. The nanomedicine is based on poly(β-amino-ester)-coated gold nanocages (AuNCs), which is further incorporated with the phase-change material (lauric acid/stearic acid, LA/SA). Following intra-articular (IA) injection in vivo, the nanomedicine displays high degree of drug accumulation and retention in the joint lesion of OA mouse models. The photothermal effect, induced by AuNCs, not only promotes DIA and siRNA release, but also upregulates the expression of heat shock protein 70 (HSP-70) to resist the apoptosis of chondrocytes in the inflammatory condition. The internalization of both DIA and siRNA results in strong anti-inflammatory and pain-relieving effects, which greatly contribute to the joint repair of OA mice. This study offers a promising combination strategy for OA treatment.
