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Published on: December 22, 2010
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Development of surface functionalized hydroxyapatite nanoparticles for enhanced specificity towards tumor cells
Gunjan Verma1, Neena G Shetake2, Shruti Pandrekar3
1Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085, India; Homi Bhabha National Institute, Anushaktinagar, Mumbai 400 094, India.
Summary
This study developed targeted nanoparticles for cancer therapy. Folate-conjugated hydroxyapatite nanoparticles loaded with doxorubicin showed effective drug delivery and cancer cell toxicity, particularly in folate receptor-overexpressing cells.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cancer Therapeutics
Background:
- Targeted drug delivery systems are crucial for enhancing cancer therapy efficacy and minimizing chemotherapy side effects.
- Hydroxyapatite nanoparticles offer a versatile platform for drug encapsulation and functionalization.
- Folic acid conjugation can facilitate targeted delivery to cancer cells overexpressing folate receptors.
Purpose of the Study:
- To develop surface-functionalized hydroxyapatite nanoparticles for dual targeting and drug delivery.
- To conjugate folic acid (FA) as a targeting ligand and doxorubicin hydrochloride (DOX) as an anticancer drug to hydroxyapatite nanoparticles via gelatin.
- To evaluate the drug release profile, cytotoxicity, and cellular uptake of the developed nanoparticles.
Main Methods:
- Hydroxyapatite nanoparticles were synthesized and functionalized with gelatin.
- Folic acid was chemically conjugated to the nanoparticles using EDCNHS coupling.
- Drug loading, release kinetics, material characterization (XRD, FTIR, TGA, UV-Vis), cytotoxicity assays, cellular uptake studies (confocal microscopy, flow cytometry), and cell cycle analysis were performed.
Main Results:
- Successful synthesis of FA-conjugated gelatin-coated hydroxyapatite nanoparticles (FA-Gel-HANPs) with dual functionality.
- Demonstrated pH-responsive, sustained release of doxorubicin (DOX) from nanoparticles, with higher release rates at acidic pH.
- DOX-loaded nanoparticles (DOX-FA-Gel-HANPs) exhibited significant cytotoxicity against cancer cell lines, with highest efficacy against folate receptor-overexpressing KB cells.
- Enhanced cellular uptake of DOX-FA-Gel-HANPs was observed in KB cells compared to folate receptor-deficient WRL-68 cells.
- Cell cycle analysis indicated apoptosis induction in KB cells.
Conclusions:
- DOX-FA-Gel-HANPs represent a promising tumor-targeted drug delivery system.
- The developed nanoparticles demonstrate effective drug release and targeted cytotoxicity.
- This approach holds potential for improving cancer treatment outcomes by enhancing drug delivery specificity and efficacy.
