[Experimental study on 5-fluourouracil-loaded immunonanoparticles targeting to lens epithelial cells].
OBJECTIVE
To evaluate the immunological characteristics of an immunonanoparticles targeting to human lens epithelial cells and to study if it could internalize into and inhibit the proliferation of target cells in vitro.


METHODS
Crosslinker carbodiimide was used to couple McAb HILE6 (anti-lens epithelial cells antibody) with 5-fluourouracil-loaded polyactic acid nanoparticles PLA (5-FU)-NP to prepare the immunonanoparticles HILE6-PLA (5-FU)-NP. The molar ratio of HILE6 and 5-FU in the immunonanoparticles were observed. The immunological activity of the antibodies in the immunonanoparticles was assessed by ELISA. The third passage lens epithelial cells were divided into four groups; immunonanoparticles, 5-FU nanoparticles, mixed HILE6 and 5-FU nanoparticles and the controls. The proliferation of lens epithelial cells were evaluated by MTT analysis. Internalization of immunonanoparticles, 5-FU nanoparticles and McAb HILE6 were observed by indirect immunofluorescence study of lens epithelial cells.


RESULTS
The molar ratio of 5-FU to HILE6 in the immunonanoparticles was 1809:1 and 84% of the original immunological activity of antibodies could be retained. The immunonanoparticles inhibited the proliferation of lens epithelial cells, which was significantly greater than original 5-FU nanoparticles or the blend group. The IC(50) inhibition of immunonanoparticles was 5.0 microg/ml 2 hours after treatment. The immunonanoparticles were bound to the cells surface in 30 minutes; internalized in 2 hours and accumulated around the nucleus after 4 hours.


CONCLUSIONS
The immunonanoparticles retain immunological activity and could specifically internalize into the lens epithelial cells to inhibit their proliferation.
Li
Xiao-rong
XR
Eye Centre, Tianjin Medical University, Tianjin 300070, China.
Liu
Xin-ling
XL
Chang
Jin
J
Liu
Xiao-yan
XY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D000963:Antimetabolites / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000166:cytology* / Q000276:immunology; D036103:Nanotechnology / Q000379:methods; D011817:Rabbits
D000911:Antibodies, Monoclonal; D000963:Antimetabolites; D004337:Drug Carriers; D005472:Fluorouracil