Details

Autor(en) / Beteiligte

• Xu, Jianbin
• Li, Jinming
• Lin, Sien
• Wu, Tianyi
• Huang, Heqin
• Zhang, Kunyu
• Sun, Yuxin
• Yeung, Kelvin W. K.
• Li, Gang
• Bian, Liming

Titel

Nanocarrier-Mediated Codelivery of Small Molecular Drugs and siRNA to Enhance Chondrogenic Differentiation and Suppress Hypertrophy of Human Mesenchymal Stem Cells

Ist Teil von

• Advanced functional materials, 2016-04, Vol.26 (15), p.2463-2472

Ort / Verlag

Blackwell Publishing Ltd

Erscheinungsjahr

2016

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• Cartilage loss is a leading cause of disability among adults, and effective therapy remains elusive. Human mesenchymal stem cells (hMSCs), which have demonstrated self‐renewal and multipotential differentiation, are a promising cell source for cartilage repair. However, the hypertrophic differentiation of the chondrogenically induced MSCs and resulting tissue calcification hinders the clinical translation of MSCs for cartilage repair. Here, a multifunctional nanocarrier based on quantum dots (QDs) is developed to enhance chondrogenic differentiation and suppress hypertrophy of hMSCs simultaneously. Briefly, the QDs are modified with β‐cyclodextrin (β‐CD) and RGD peptide. The resulting nanocarrier is capable of carrying hydrophobic small molecules such as kartogenin in the hydrophobic pockets of conjugated β‐CD to induce chondrogenic differentiation of hMSCs. Meanwhile, via electrostatic interaction the conjugated RGD peptides bind the cargo siRNA targeting Runx2, which is a key regulator of hMSC hypertrophy. Furthermore, due to the excellent photostability of QDs, hMSCs labeled with the nanocarrier can be tracked for up to 14 d after implantation in nude mice. Overall, this work demonstrates the potential of our nanocarrier for inducing and maintaining the chondrogenic phenotype and tracking hMSCs in vivo. A multifunctional quantum dot‐based nanocarrier for the efficient and controlled codelivery of small molecule drugs and siRNAs is developed. Codelivery of chondrogenic small molecules and anti‐hypertrophy siRNA using this nanocarrier markedly enhances the chondrogenesis of human mesenchymal stem cells and neocartilage development while suppressing the hypertrophic differentiation and the associated cartilage calcification.