Polymer chemistry influences monocytic uptake of polyanhydride nanospheres.
OBJECTIVE
To demonstrate that polyanhydride copolymer chemistry affects the uptake and intracellular compartmentalization of nanospheres by THP-1 human monocytic cells.


METHODS
Polyanhydride nanospheres were prepared by an anti-solvent nanoprecipitation technique. Morphology and particle diameter were confirmed via scanning election microscopy and quasi-elastic light scattering, respectively. The effects of varying polymer chemistry on nanosphere and fluorescently labeled protein uptake by THP-1 cells were monitored by laser scanning confocal microscopy.


RESULTS
Polyanhydride nanoparticles composed of poly(sebacic anhydride) (SA), and 20:80 and 50:50 copolymers of 1,6-bis-(p-carboxyphenoxy)hexane (CPH) anhydride and SA were fabricated with similar spherical morphology and particle diameter (200 to 800 nm). Exposure of the nanospheres to THP-1 monocytes showed that poly(SA) and 20:80 CPH:SA nanospheres were readily internalized whereas 50:50 CPH:SA nanospheres had limited uptake. The chemistries also differentially enhanced the uptake of a red fluorescent protein-labeled antigen.


CONCLUSIONS
Nanosphere and antigen uptake by monocytes can be directly correlated to the chemistry of the nanosphere. These results demonstrate the importance of choosing polyanhydride chemistries that facilitate enhanced interactions with antigen presenting cells that are necessary in the initiation of efficacious immune responses.
Ulery
Bret D
BD
Department of Chemical and Biological Engineering, Iowa State University, Ames, IOWA, 50011, USA.
Phanse
Yashdeep
Y
Sinha
Avanti
A
Wannemuehler
Michael J
MJ
Narasimhan
Balaji
B
Bellaire
Bryan H
BH
D000938:Antigen-Presenting Cells; D000954:Antigens, Surface / Q000008:administration & dosage; D002460:Cell Line; D011232:Chemical Precipitation; D003652:Decanoic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D003998:Dicarboxylic Acids / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000378:metabolism*; D054118:Nanospheres / Q000737:chemistry*; D010316:Particle Size; D049388:Polyanhydrides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013499:Surface Properties; D014612:Vaccines / Q000008:administration & dosage
C120991:1,6-bis(carboxyphenoxy)hexane; D000954:Antigens, Surface; D003652:Decanoic Acids; D003998:Dicarboxylic Acids; D004337:Drug Carriers; D006586:Hexanes; D049388:Polyanhydrides; D011091:Polyesters; D014612:Vaccines; C466992:poly((1,6-bis-4-carboxyphenoxyhexane)-co-(sebacic anhydride)); C011107:sebacic acid