Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 26, Issue 15, Pages 2463-2472Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201504070
Keywords
drug and gene delivery; in vivo imaging; nanoparticle; stem cell differentiation
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Funding
- Research Grants Council of Hong Kong [439913]
- Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong [BME-p3-15]
- National Natural Science Foundation of China [31570979]
- Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong
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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 beta-cyclodextrin (beta-CD) and RGD peptide. The resulting nanocarrier is capable of carrying hydrophobic small molecules such as kartogenin in the hydrophobic pockets of conjugated beta-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.
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