Receptor-mediated gene delivery using PAMAM dendrimers conjugated with peptides recognized by mesenchymal stem cells.
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.
CQM-Centro de Quimica da Madeira, MMRG, Departamento de Quimica, Universidade da Madeira, Campus Universitario da Penteada, 9000-390 Funchal, Portugal.
José L
JL
Santos
Deepti
D
Pandita
João
J
Rodrigues
Ana P
AP
Pêgo
Pedro L
PL
Granja
Gary
G
Balian
Helena
H
Tomás
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D050091:Dendrimers / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry* / Q000378:metabolism*; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008962:Models, Theoretical; D010455:Peptides / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
D050091:Dendrimers; C104700:PAMAM Starburst; D010455:Peptides; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins