Therapeutic cell engineering with surface-conjugated synthetic nanoparticles.
A major limitation of cell therapies is the rapid decline in viability and function of the transplanted cells. Here we describe a strategy to enhance cell therapy via the conjugation of adjuvant drug-loaded nanoparticles to the surfaces of therapeutic cells. With this method of providing sustained pseudoautocrine stimulation to donor cells, we elicited marked enhancements in tumor elimination in a model of adoptive T cell therapy for cancer. We also increased the in vivo repopulation rate of hematopoietic stem cell grafts with very low doses of adjuvant drugs that were ineffective when given systemically. This approach is a simple and generalizable strategy to augment cytoreagents while minimizing the systemic side effects of adjuvant drugs. In addition, these results suggest therapeutic cells are promising vectors for actively targeted drug delivery.
Stephan
Matthias T
MT
Department of Material Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Moon
James J
JJ
Um
Soong Ho
SH
Bershteyn
Anna
A
Irvine
Darrell J
DJ
D000818:Animals; D001698:Biomedical Engineering / Q000379:methods*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004337:Drug Carriers / Q000627:therapeutic use; D048888:Fireflies / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000235:genetics; D049449:Luminescence; D051379:Mice; D053758:Nanoparticles / Q000627:therapeutic use*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D030781:Organisms, Genetically Modified / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods; D013499:Surface Properties; D013601:T-Lymphocytes / Q000276:immunology*
D004337:Drug Carriers; D008156:Luciferases