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Targeted Delivery of 5-fluorouracil with Monoclonal Antibody Modified Bovine Serum Albumin Nanoparticles.

Fadaeian G, Shojaosadati SA, Kouchakzadeh H, Shokri F, Soleimani M - Iran J Pharm Res (2015)

Bottom Line: No cellular uptake was observed for HER2-negative MCF7 cells.Physicochemical and biological properties of the mAb-modified nanoparticles did not significantly alter after three months of storage at room temperature.This novel system can efficiently be employed for targeted delivery of 5-FU to HER2-positive cancerous cells.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Group, Chemical Engineering Faculty , Tarbiat Modares University, Tehran, Iran.

ABSTRACT
Herein, 1F2, an anti-HER2 monoclonal antibody (mAb), was covalently coupled to the surface of 5-Fluorouracil (5-FU) loaded bovine serum albumin (BSA) nanoparticles. Concerning two different crosslinkers for conjugation of 1F2, Maleimide-poly (ethylene glycol)-Succinimidyl carbonate (Mal-PEG5000-NHS) was selected due to its higher conjugation efficiency (23 ± 4%) obtained in comparison to N-succinimidyl 3-(2-Pyridyl Dithio) Propionate (SPDP) (8 ± 2%). A slight increase in the average particle size with a negligible prolongation of the 5-FU release was observed after 1F2 coupling. The 1F2-coupled 5-FU-loaded BSA nanoparticles interacted with nearly all HER2 receptors available on the surface of HER2-positive SKBR3 cells. No cellular uptake was observed for HER2-negative MCF7 cells. Physicochemical and biological properties of the mAb-modified nanoparticles did not significantly alter after three months of storage at room temperature. The in-vitro cytotoxicity evaluation by MTT assay, demonstrated lower SKBR3 viability (50.7 ± 9 %) after 5 hours contact with 1F2-coupled 5-FU-loaded BSA nanoparticles in comparison with the other control systems due to their cell attachment and internalization after washing. In addition, no significant toxicity was observed on MCF7 cells. This novel system can efficiently be employed for targeted delivery of 5-FU to HER2-positive cancerous cells.

No MeSH data available.


Related in: MedlinePlus

SEM micrograph of 1F2-coupled 5-FU-loaded BSA nanoparticles at magnification of 30000X
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Figure 2: SEM micrograph of 1F2-coupled 5-FU-loaded BSA nanoparticles at magnification of 30000X

Mentions: 5-FU-loaded BSA nanoparticles were characterized in terms of particle size, PDI and zeta potential by DLS (Table 1). The average particle size of 1F2-conjugated 5- FU-loaded BSA nanoparticles was found to be 197 nm, which is higher than 5-FU-loaded BSA nanoparticles and approximately the same as PEGylated BSA nanoparticles. The mean PDI of 1F2-modified BSA nanoparticles is 0.051 that verifies their narrow size distribution. 1F2-modified BSA nanoparticles showed the surface charge of -22.5 mV. 1F2 mAb coupling did not significantly change the physicochemical properties of 5-FU-loaded BSA nanoparticles, which are in the proper range to be used in targeted drug delivery (17-21, 23-25). SEM analyses of 1F2-coupled 5-FU-loaded BSA nanoparticles verified their spherical morphology (Figure 2) as described previously (17, 25, 26).


Targeted Delivery of 5-fluorouracil with Monoclonal Antibody Modified Bovine Serum Albumin Nanoparticles.

Fadaeian G, Shojaosadati SA, Kouchakzadeh H, Shokri F, Soleimani M - Iran J Pharm Res (2015)

SEM micrograph of 1F2-coupled 5-FU-loaded BSA nanoparticles at magnification of 30000X
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403055&req=5

Figure 2: SEM micrograph of 1F2-coupled 5-FU-loaded BSA nanoparticles at magnification of 30000X
Mentions: 5-FU-loaded BSA nanoparticles were characterized in terms of particle size, PDI and zeta potential by DLS (Table 1). The average particle size of 1F2-conjugated 5- FU-loaded BSA nanoparticles was found to be 197 nm, which is higher than 5-FU-loaded BSA nanoparticles and approximately the same as PEGylated BSA nanoparticles. The mean PDI of 1F2-modified BSA nanoparticles is 0.051 that verifies their narrow size distribution. 1F2-modified BSA nanoparticles showed the surface charge of -22.5 mV. 1F2 mAb coupling did not significantly change the physicochemical properties of 5-FU-loaded BSA nanoparticles, which are in the proper range to be used in targeted drug delivery (17-21, 23-25). SEM analyses of 1F2-coupled 5-FU-loaded BSA nanoparticles verified their spherical morphology (Figure 2) as described previously (17, 25, 26).

Bottom Line: No cellular uptake was observed for HER2-negative MCF7 cells.Physicochemical and biological properties of the mAb-modified nanoparticles did not significantly alter after three months of storage at room temperature.This novel system can efficiently be employed for targeted delivery of 5-FU to HER2-positive cancerous cells.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Group, Chemical Engineering Faculty , Tarbiat Modares University, Tehran, Iran.

ABSTRACT
Herein, 1F2, an anti-HER2 monoclonal antibody (mAb), was covalently coupled to the surface of 5-Fluorouracil (5-FU) loaded bovine serum albumin (BSA) nanoparticles. Concerning two different crosslinkers for conjugation of 1F2, Maleimide-poly (ethylene glycol)-Succinimidyl carbonate (Mal-PEG5000-NHS) was selected due to its higher conjugation efficiency (23 ± 4%) obtained in comparison to N-succinimidyl 3-(2-Pyridyl Dithio) Propionate (SPDP) (8 ± 2%). A slight increase in the average particle size with a negligible prolongation of the 5-FU release was observed after 1F2 coupling. The 1F2-coupled 5-FU-loaded BSA nanoparticles interacted with nearly all HER2 receptors available on the surface of HER2-positive SKBR3 cells. No cellular uptake was observed for HER2-negative MCF7 cells. Physicochemical and biological properties of the mAb-modified nanoparticles did not significantly alter after three months of storage at room temperature. The in-vitro cytotoxicity evaluation by MTT assay, demonstrated lower SKBR3 viability (50.7 ± 9 %) after 5 hours contact with 1F2-coupled 5-FU-loaded BSA nanoparticles in comparison with the other control systems due to their cell attachment and internalization after washing. In addition, no significant toxicity was observed on MCF7 cells. This novel system can efficiently be employed for targeted delivery of 5-FU to HER2-positive cancerous cells.

No MeSH data available.


Related in: MedlinePlus