Type
Text
Type
Thesis
Advisor
T, Venkatesh | Meng, Yizhi | Balázsi, Gábor.
Date
2017-05-01
Keywords
Materials Science | Alendronate, Breast cancer, HGC nanoparticles, Hydrophobically modified glycol chitosan, Microcalcification, Nanoparticle targeting
Department
Department of Materials Science and Engineering
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/76164
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
Abstract
In 2016, invasive breast cancer was diagnosed in about 246,660 women and 2,600 men. An additional 61,000 new cases of in situ breast cancer was diagnosed in women. Microcalcifications are most common abnormalities detected by mammography for breast cancer, present in about 30% of all malignant breast lesions. Tumor specific biomarkers are used for targeting these abnormalities. Nanoparticles with multimodal and combinatorial therapies and conjunction of bio-ligands for specific molecular targeting using surface modifications effectually deliver a variety of drugs and are simultaneously used to image tumor progression. Alendronate, a germinal bisphosphonate conjugation as a targeting ligand would improve the nanoparticle’s direct binding to hydroxyapatite (HA) mimicking calcified spots in breast cancer lesions. In this study, the hydrophobically modified glycol chitosan (HGC) micelle was modified with alendronate surface functionalization using a biotin-avidin interaction to improve the nanomicelle’s calcification targeting ability. Biotinylated, avidinlyated hydrophobically modified iv glycol chitosan particles were linked to biotinylated alendronate via a strong biotin-avidin linkage. Cyanine 3, a red fluorescent dye was conjugated to the amine groups on HGC for visualization of micelles. The size of the nanoparticles measured was 254.0 ± 0.43 nm and 209.7 ± 1.0 nm for Cy3- BHGCA and Cy3-BHGCA-BALN nanoparticles respectively. The average surface charge was measured to be +26.9 ± 0.19 mV and +27.68 ± 0.20 mV for Cy3-BHGCA and Cy3-BHGCA- BALN nanoparticles respectively. Binding affinity using hydroxyapatite (HA) revealed that both Cy3 BHGCA BALN and Cy3 BHGCA nanoparticles displayed 95% binding in 24 hours. However, the biotin quenched nanoparticle Cy3 BHGCAB displayed 68% binding in 24 hours. The synthesis and binding chemistry was verified using Fourier transform infrared spectroscopy (FTIR). | In 2016, invasive breast cancer was diagnosed in about 246,660 women and 2,600 men. An additional 61,000 new cases of in situ breast cancer was diagnosed in women. Microcalcifications are most common abnormalities detected by mammography for breast cancer, present in about 30% of all malignant breast lesions. Tumor specific biomarkers are used for targeting these abnormalities. Nanoparticles with multimodal and combinatorial therapies and conjunction of bio-ligands for specific molecular targeting using surface modifications effectually deliver a variety of drugs and are simultaneously used to image tumor progression. Alendronate, a germinal bisphosphonate conjugation as a targeting ligand would improve the nanoparticle’s direct binding to hydroxyapatite (HA) mimicking calcified spots in breast cancer lesions. In this study, the hydrophobically modified glycol chitosan (HGC) micelle was modified with alendronate surface functionalization using a biotin-avidin interaction to improve the nanomicelle’s calcification targeting ability. Biotinylated, avidinlyated hydrophobically modified iv glycol chitosan particles were linked to biotinylated alendronate via a strong biotin-avidin linkage. Cyanine 3, a red fluorescent dye was conjugated to the amine groups on HGC for visualization of micelles. The size of the nanoparticles measured was 254.0 ± 0.43 nm and 209.7 ± 1.0 nm for Cy3- BHGCA and Cy3-BHGCA-BALN nanoparticles respectively. The average surface charge was measured to be +26.9 ± 0.19 mV and +27.68 ± 0.20 mV for Cy3-BHGCA and Cy3-BHGCA- BALN nanoparticles respectively. Binding affinity using hydroxyapatite (HA) revealed that both Cy3 BHGCA BALN and Cy3 BHGCA nanoparticles displayed 95% binding in 24 hours. However, the biotin quenched nanoparticle Cy3 BHGCAB displayed 68% binding in 24 hours. The synthesis and binding chemistry was verified using Fourier transform infrared spectroscopy (FTIR). | 93 pages
Recommended Citation
Vishnu, Kamalakannan, "Hydrophobically modified glycol chitosan nanoparticles for targeting breast cancer microcalcification using alendronate probes" (2017). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 2106.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/2106