Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells
Selective targeting of cells for intracellular delivery of therapeutics represents a major challenge for pharmaceutical intervention in disease. Here we show pH triggered receptor-mediated endocytosis of nanoparticles via surface ligand exposure. Gold nanoparticles were decorated with two polymers:...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Published: |
Royal Society of Chemistry
2017
|
| Online Access: | https://eprints.nottingham.ac.uk/44261/ |
| _version_ | 1848796874531667968 |
|---|---|
| author | Brazzale, C. Mastrotto, Francesca Moody, P. Watson, P.D. Balasso, A. Malfanti, A. Mantovani, Giuseppe Caliceti, Paolo Alexander, Cameron Jones, A.T. Salmaso, Stefano |
| author_facet | Brazzale, C. Mastrotto, Francesca Moody, P. Watson, P.D. Balasso, A. Malfanti, A. Mantovani, Giuseppe Caliceti, Paolo Alexander, Cameron Jones, A.T. Salmaso, Stefano |
| author_sort | Brazzale, C. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Selective targeting of cells for intracellular delivery of therapeutics represents a major challenge for pharmaceutical intervention in disease. Here we show pH triggered receptor-mediated endocytosis of nanoparticles via surface ligand exposure. Gold nanoparticles were decorated with two polymers: a 2 kDa PEG with a terminal folate targeting ligand, and a di-block copolymer including a pH-responsive and a hydrophilic block. At the normal serum pH of 7.4, the pH-responsive block (apparent pKa of 7.1) displayed a hydrophilic extended conformation, shielding the PEG-folate ligands, which inhibited cellular uptake of the nanoparticles. Under pH conditions resembling those of the extracellular matrix around solid tumours (pH 6.5), protonation of the pH-responsive polymer triggered a coil-to-globule polymer chain contraction, exposing folate residues on the PEG chains. In line with this, endocytosis of folate-decorated polymer-coated gold nanoparticles in cancer cells overexpressing folate receptor was significantly increased at pH 6.5, compared with pH 7.4. Thus, the tumour acidic environment and high folate receptor expression was effectively exploited to activate cell binding and endocytosis of these nanoparticles. These data provide proof-of-concept for strategies enabling extracellular pH stimuli to selectively enhance cellular uptake of drug delivery vectors and their associated therapeutic cargo. |
| first_indexed | 2025-11-14T19:54:55Z |
| format | Article |
| id | nottingham-44261 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:54:55Z |
| publishDate | 2017 |
| publisher | Royal Society of Chemistry |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-442612020-05-04T18:55:26Z https://eprints.nottingham.ac.uk/44261/ Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells Brazzale, C. Mastrotto, Francesca Moody, P. Watson, P.D. Balasso, A. Malfanti, A. Mantovani, Giuseppe Caliceti, Paolo Alexander, Cameron Jones, A.T. Salmaso, Stefano Selective targeting of cells for intracellular delivery of therapeutics represents a major challenge for pharmaceutical intervention in disease. Here we show pH triggered receptor-mediated endocytosis of nanoparticles via surface ligand exposure. Gold nanoparticles were decorated with two polymers: a 2 kDa PEG with a terminal folate targeting ligand, and a di-block copolymer including a pH-responsive and a hydrophilic block. At the normal serum pH of 7.4, the pH-responsive block (apparent pKa of 7.1) displayed a hydrophilic extended conformation, shielding the PEG-folate ligands, which inhibited cellular uptake of the nanoparticles. Under pH conditions resembling those of the extracellular matrix around solid tumours (pH 6.5), protonation of the pH-responsive polymer triggered a coil-to-globule polymer chain contraction, exposing folate residues on the PEG chains. In line with this, endocytosis of folate-decorated polymer-coated gold nanoparticles in cancer cells overexpressing folate receptor was significantly increased at pH 6.5, compared with pH 7.4. Thus, the tumour acidic environment and high folate receptor expression was effectively exploited to activate cell binding and endocytosis of these nanoparticles. These data provide proof-of-concept for strategies enabling extracellular pH stimuli to selectively enhance cellular uptake of drug delivery vectors and their associated therapeutic cargo. Royal Society of Chemistry 2017-07-14 Article PeerReviewed Brazzale, C., Mastrotto, Francesca, Moody, P., Watson, P.D., Balasso, A., Malfanti, A., Mantovani, Giuseppe, Caliceti, Paolo, Alexander, Cameron, Jones, A.T. and Salmaso, Stefano (2017) Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells. Nanoscale, 9 (31). pp. 11137-11147. ISSN 2040-3372 http://pubs.rsc.org/en/Content/ArticleLanding/2017/NR/C7NR02595E#!divAbstract doi:10.1039/C7NR02595E doi:10.1039/C7NR02595E |
| spellingShingle | Brazzale, C. Mastrotto, Francesca Moody, P. Watson, P.D. Balasso, A. Malfanti, A. Mantovani, Giuseppe Caliceti, Paolo Alexander, Cameron Jones, A.T. Salmaso, Stefano Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells |
| title | Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells |
| title_full | Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells |
| title_fullStr | Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells |
| title_full_unstemmed | Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells |
| title_short | Control of targeting ligand display by pH-responsive polymers on gold nanoparticles mediates selective entry into cancer cells |
| title_sort | control of targeting ligand display by ph-responsive polymers on gold nanoparticles mediates selective entry into cancer cells |
| url | https://eprints.nottingham.ac.uk/44261/ https://eprints.nottingham.ac.uk/44261/ https://eprints.nottingham.ac.uk/44261/ |