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[Experimental study on 5-fluourouracil-loaded immunonanoparticles targeting to lens epithelial cells]
Xiao-rong Li1, Xin-ling Liu, Jin Chang
1Eye Centre, Tianjin Medical University, Tianjin 300070, China.
Insights
Novel immunonanoparticles targeting lens epithelial cells retain activity and effectively inhibit cell proliferation in vitro. These targeted nanoparticles show promise for therapeutic applications.
Area of Science:
- Ophthalmology
- Nanotechnology
- Immunology
Context:
- Human lens epithelial cells (hLECs) are crucial for maintaining ocular health.
- Uncontrolled hLEC proliferation can lead to conditions like cataracts and fibrosis.
- Targeted drug delivery systems are needed to improve treatment efficacy and reduce side effects.
Purpose:
- To develop and characterize immunonanoparticles targeting hLECs.
- To evaluate the immunological activity and internalization of these immunonanoparticles.
- To assess the efficacy of immunonanoparticles in inhibiting hLEC proliferation in vitro.
Summary:
- Immunonanoparticles were synthesized by coupling anti-hLEC antibodies (McAb HILE6) to 5-fluorouracil-loaded poly(lactic acid) nanoparticles (5-FU-PLA-NP).
- The immunonanoparticles (HILE6-PLA (5-FU)-NP) retained 84% of the antibody's immunological activity.
- These targeted nanoparticles demonstrated significantly greater inhibition of hLEC proliferation compared to non-targeted nanoparticles, with an IC50 of 5.0 μg/mL.
Impact:
- The study demonstrates successful targeted delivery and inhibition of hLEC proliferation using immunonanoparticles.
- This approach offers a potential strategy for developing novel treatments for ocular diseases driven by hLEC dysfunction.
- Further research may lead to improved therapeutic outcomes in ophthalmology through targeted nanomedicine.
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.
Conclusion:
The immunonanoparticles retain immunological activity and could specifically internalize into the lens epithelial cells to inhibit their proliferation.
