Citation: Xueyan Zhang, Jicong Chen, Songren Han, Shiyan Dong, Huan Zhang, Yuhong Man, Jie Yang, Ye Bi, Lesheng Teng. The size-switchable microspheres co-loaded with RANK siRNA and salmon calcitonin for osteoporosis therapy[J]. Chinese Chemical Letters, ;2024, 35(12): 109668. doi: 10.1016/j.cclet.2024.109668 shu

The size-switchable microspheres co-loaded with RANK siRNA and salmon calcitonin for osteoporosis therapy

Xueyan Zhang ^a ,
Jicong Chen ^a ,
Songren Han ^a ,
Shiyan Dong ^b ,
Huan Zhang ^a ,
Yuhong Man ^d ,
Jie Yang ^{a, *,} ,
Ye Bi ^{c, *,} ,
Lesheng Teng ^{a, *,}

a.
School of Life Sciences, Jilin University, Changchun 130012, China
b.
Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston 77030, TX, United States
c.
Practice Training Center, Changchun University of Chinese Medicine, Changchun 130117, China
d.
Department of Neurology, The Second Hospital of Jilin University, Changchun 130041, China

jieyang@jlu.edu.cn

biye88@outlook.com

tenglesheng@jlu.edu.cn

Received Date: 13 December 2023
Revised Date: 15 February 2024
Accepted Date: 17 February 2024
Available Online: 24 February 2024

Figures(4)

Osteoporosis is a disease of bone metabolism homeostasis imbalance with obvious bone loss, damage to bone microstructure, and increased risk of fracture. The occurrence and development of osteoporosis is related to the augmentation of active osteoclasts. Receptor activator of nuclear factor kappa B (RANK) small interfering RNA (siRNA) knockdowns the expression of RANK mRNA to inhibit the osteoclast precursors differentiate into osteoclasts as a treatment in osteoporosis. Salmon calcitonin (sCT) is a commonly used anti-osteoporotic agent that inhibits osteoclast activity and induces osteoclast apoptosis, and it also could promote the osteogenesis by osteoblasts. A cocktail therapy improves the therapeutic effect of osteoporosis between RANK siRNA and sCT. A size-switchable microsphere from micro to nano scale was developed to address the delivery barriers of biomacromolecules with poor stability and frequent administration. RANK siRNA and sCT were incorporated into the microspheres with a nanoparticle/micelle-microsphere double-layer structure to achieve sustained release when the particle size shrunk and dual protection of RANK siRNA and sCT. The size-switchable microspheres MS@(AL-NPs/ARM) had an optimal therapeutic effect and reduced the frequency of administration in glucocorticoid induced osteoporosis (GIOP) mouse model. RANK siRNA and sCT co-delivery system based on size-switchable microsphere is a promising strategy to treat osteoporosis through the controlled release of biomacromolecules.
- Osteoporosis,
- RANK siRNA,
- Salmon calcitonin,
- Nanocarriers,
- Size-switchable microspheres
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