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. 2011 Apr 22;85(1):215-220.
doi: 10.1016/j.carbpol.2011.02.018.

N,N,N-Trimethyl chitosan nanoparticles for the delivery of monoclonal antibodies against hepatocellular carcinoma cells

Preeyanat Vongchan  1 , Yupanan Wutti-In, Warayuth Sajomsang, Pattarapond Gonil, Suchart Kothan, Robert J Linhardt
Affiliations

N,N,N-Trimethyl chitosan nanoparticles for the delivery of monoclonal antibodies against hepatocellular carcinoma cells

Preeyanat Vongchan et al. Carbohydr Polym. .

Abstract

N,N,N-Trimethyl chitosan chloride is capable of forming nanocomplexes with protein through ionotropic gelation. A monoclonal antibody, raised against human liver heparan sulfate proteoglycan and specifically inhibiting hepatocellular carcinoma in vitro, was prepared in nanocomplexes of this modified chitosan. The smallest nanocomplexes (59 ± 17 nm, zeta-potential 16.5 ± 0.5 mV) were obtained at polysaccharide:antibody ratios of 5:0.3. Spherical particles with a smooth surface and compact structure having a mean diameter of ~11.2 ± 0.09 nm were investigated by Atomic Force Microscopy. Cellular uptake of fluorescently labeled nanocomplexes was studied in mouse monocyte models of cancer and normal cells. External and internal fluorescence was analyzed by flow cytometry. The results demonstrate that the nanocomplexes could enter cells and were retained for a longer period of time in cancer cells where they exhibited greater toxicity. These nanocomplexes appear safe and could potentially enhance the half-life of added antibodies.

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Figures

Figure 1
Figure 1
The particle sizes and zeta-potentials of TM-chitosan:monoclonal antibody (MAb) with various concentrations ratios 2:0.3, 5:0.3 and 10:0.3
Figure 2
Figure 2
AFM images of TM-chitosan:monoclonal antibody (MAb) (5:0.3); topology images (a), phase images (b)
Figure 3
Figure 3
The fluorescence intensity of TM-chitosan/1E4-1C2-FITC and 1E4-1C2-FITC plots as a function of time. HepG2 cell incubated with TM-chitosan/1E4-1C2-FITC and 1E4-1C2-FITC in various time and then, the total fluorescence intensity were recorded (a). The ratio of external to internal fluorescence intensity of TM-chitosan/1E4-1C2-FITC and 1E4-1C2-FITC were measured (b). In saturation with 1E4-1C2, the total fluorescence intensity of TM-chitosan/1E4-1C2-FITC and 1E4-1C2-FITC in cell were recorded (c).
Figure 4
Figure 4
HepG2 cells and PBMCs were incubated with various concentrations (0–80 µg/mL) of TM-chitosan.
See this image and copyright information in PMC

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