Dual-surface modified virus capsids for targeted delivery of photodynamic agents to cancer cells.
Bacteriophage MS2 was used to construct a targeted, multivalent photodynamic therapy vehicle for the treatment of Jurkat leukemia T cells. The self-assembling spherical virus capsid was modified on the interior surface with up to 180 porphyrins capable of generating cytotoxic singlet oxygen upon illumination. The exterior of the capsid was modified with ∼20 copies of a Jurkat-specific aptamer using an oxidative coupling reaction targeting an unnatural amino acid. The capsids were able to target and selectively kill more than 76% of the Jurkat cells after only 20 min of illumination. Capsids modified with a control DNA strand did not target Jurkat cells, and capsids modified with the aptamer were found to be specific for Jurkat cells over U266 cells (a control B cell line). The doubly modified capsids were also able to kill Jurkat cells selectively even when mixed with erythrocytes, suggesting the possibility of using our system to target blood-borne cancers or other pathogens in the blood supply.
Stephanopoulos
Nicholas
N
Department of Chemistry, University of California, Berkeley, and Materials Sciences Division, Lawrence Berkeley National Laboratories, Berkeley, California 94720-1460, USA.
Tong
Gary J
GJ
Hsiao
Sonny C
SC
Francis
Matthew B
MB
D052157:Aptamers, Nucleotide; D001402:B-Lymphocytes / Q000378:metabolism; D002213:Capsid / Q000737:chemistry*; D036022:Capsid Proteins / Q000737:chemistry*; D002460:Cell Line; D016503:Drug Delivery Systems; D004912:Erythrocytes / Q000166:cytology; D006801:Humans; D019169:Jurkat Cells; D017909:Levivirus / Q000378:metabolism; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins; D026082:Singlet Oxygen / Q000737:chemistry; D013053:Spectrophotometry / Q000379:methods
D052157:Aptamers, Nucleotide; D036022:Capsid Proteins; D011166:Porphyrins; D026082:Singlet Oxygen