In Situ Functionalized Polymers for siRNA Delivery
Juan M. Priegue
Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782 Spain
Search for more papers by this authorDaniel N. Crisan
School of Chemistry, University of Birmingham, B15 2TT UK
Search for more papers by this authorDr. José Martínez-Costas
Departamento de Bioquimica y Biología Molecular, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782 Spain
Search for more papers by this authorProf. Dr. Juan R. Granja
Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782 Spain
Search for more papers by this authorCorresponding Author
Dr. Francisco Fernandez-Trillo
School of Chemistry, University of Birmingham, B15 2TT UK
Search for more papers by this authorCorresponding Author
Dr. Javier Montenegro
Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782 Spain
Search for more papers by this authorJuan M. Priegue
Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782 Spain
Search for more papers by this authorDaniel N. Crisan
School of Chemistry, University of Birmingham, B15 2TT UK
Search for more papers by this authorDr. José Martínez-Costas
Departamento de Bioquimica y Biología Molecular, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782 Spain
Search for more papers by this authorProf. Dr. Juan R. Granja
Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782 Spain
Search for more papers by this authorCorresponding Author
Dr. Francisco Fernandez-Trillo
School of Chemistry, University of Birmingham, B15 2TT UK
Search for more papers by this authorCorresponding Author
Dr. Javier Montenegro
Departamento de Química Orgánica, Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares (CIQUS), Universidade de Santiago de Compostela, E-15782 Spain
Search for more papers by this authorGraphical Abstract
Signed, sealed, delivered: The chemical functionality of a polyhydrazide scaffold was modified by careful choice of cationic (blue box; see picture) and hydrophobic (red) aldehydes to produce amphiphilic vectors for supramolecular polynucleotide delivery.
Abstract
A new method is reported herein for screening the biological activity of functional polymers across a consistent degree of polymerization and in situ, that is, under aqueous conditions and without purification/isolation of candidate polymers. In brief, the chemical functionality of a poly(acryloyl hydrazide) scaffold was activated under aqueous conditions using readily available aldehydes to obtain amphiphilic polymers. The transport activity of the resulting polymers can be evaluated in situ using model membranes and living cells without the need for tedious isolation and purification steps. This technology allowed the rapid identification of a supramolecular polymeric vector with excellent efficiency and reproducibility for the delivery of siRNA into human cells (HeLa-EGFP). The reported method constitutes a blueprint for the high-throughput screening and future discovery of new polymeric functional materials with important biological applications.
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