Journal
MOLECULAR PHARMACEUTICS
Volume 7, Issue 3, Pages 763-774Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp9002877
Keywords
PAMAM dendrimers; DNA; gene delivery; cell recognition; mesenchymal stem cells
Funding
- Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [PTDC/SAU-BEB/71161/2006, SFRH/BD/19450/2004-POCI2010/FSE]
- Portuguese National Nuclear Magnetic Resonance [PTNMR-REDE/1517/RMN/2005]
- National Programme for Scientific Re-equipment [POCI 2010]
- Fundacao para a Ciencia e a Tecnologia (FCT)
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-BEB/71161/2006, SFRH/BD/135872/2018] Funding Source: FCT
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As mesenchymal stem cells (MSCs) can differentiate into multiple cell types, the delivery of exogenous genes to this type of cell can be an important tool in tissue regeneration and engineering. However transfection of MSCs using nonviral gene delivery vectors is difficult, the development of more efficient and safe DNA vehicles being necessary. Moreover, specific transfection of MSCs may be required to avoid unwanted side effects in other tissues. In this study, a novel family of gene delivery vectors based on poly(amidoamine) (PAMAM) dendrimers functionalized with peptides displaying high affinity toward MSCs was prepared. The vectors were characterized with respect to their ability to neutralize, bind and compact plasmid DNA (pDNA). The complexes formed between the vectors and pDNA were analyzed concerning their size, zeta-potential, capacity of being internalized by cells and transfection efficiency. These new vectors exhibited low cytotoxicity, receptor-mediated gene delivery into MSCs and transfection efficiencies superior to those presented by native dendrimers and by partially degraded dendrimers.
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