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Polymeric Nanoparticles for Ultrasonic Enhancement and Targeted Drug Delivery

Li, Jie
http://rave.ohiolink.edu/etdc/view?acc_num=osu1280349038

Abstract Details

2010, Master of Science, Ohio State University, Biomedical Engineering.
In this study, we aim to (1) test the feasibility of using polymeric nanoparticles for ultrasonic enhancement of tumor xenografts in mice through high frequency ultrasound system; (2) validate the nanoparticle enabled ultrasonic enhancement using diagnostic frequency ultrasound ex vivo and in vivo; and (3) develop multifunctional polymeric nanoparticles as a combined platform for ultrasound contrast enhancement and drug delivery. For Aim 1, nude mice were implanted with human breast cancer xenografts using cell lines of either MCF-7/HER2-18 (overexpressing HER2 receptors) or MDA-MB-231 (expressing HER2 at a low level). Tumors from each type were treated with anti-HER2 antibody-conjugated PLA nanoparticles via subcutaneous injection at the tumor site, or the same volume of PBS. A significant increase in ultrasonic reflectivity was observed in MCF-7/HER2-18 tumors after particle treatment (but not after PBS treatment) at 5, 15, and 30 min. No change was observed in the MDA-MB-231 tumors, suggesting that the ultrasonic enhancement may be mediated by specific binding of the surface conjugated nanoparticles to HER2 overexpressing tumor cells. For Aim 2, mouse livers were used for ex vivo study. SkBr3 human breast cancer cells (overexpressing HER2 receptors) treated with anti-HER2 antibody-conjugated PLA nanoparticle were injected into mouse livers, and the same dosage of SKBr3 cells treated with PBS only was injected into mouse livers as control. HER2/neu transgenic mice were used for in vivo study and the conjugated particles or PBS was injected subcutaneously close to the tumors. All ultrasound images were acquired by clinic ultrasound system with a 14 MHz probe. Consistently to the results from high frequency ultrasound imaging, the acoustic intensity only increased within the injection site of targeted PLA nanoparticles treated tumor cells or tumors. The maximal acoustic intensity was reached at 15 minutes after the injection in vivo. For Aim 3, a series of PLGA nanoparticles of various sizes (150, 300 and 500 nm) were fabricated by modified solvent-replacement method. Fluorescent probe was encapsulated into the nanoparticles as model drug and for tracking the nanoparticles. The targeting specificity and the resultant ultrasound enhancement were determined by fluorescent microscopy and high-resolution ultrasound imaging. The drug delivery efficiency of engineered nanoparticles was determined by observation of localization of nanoparticles in the cells via the confocal microscopy. In high-resolution ultrasound B-mode images, the average gray scale of the SkBr3 cells was significantly higher after 300 nm and 500 nm nanoparticle treatment than 100 nm nanoparticle treatment. In drug delivery study, the SkBr3 cells treated with antibody-conjugated PLGA nanoparticles of 150 nm and 300 nm demonstrated sufficient intracellular localization, while minimal intracellular localization was detected in the cells that treated with 500 nm nanoparticles. These results indicated the feasibility of using polymeric nanoparticles (PLA and PLGA) for enhanced ultrasound imaging of tumors with both high frequency and diagnostic ultrasound. Biodegradable polymeric nanoparticles may be potential agents for combined ultrasound molecular imaging and targeted drug delivery. Considering both echogenicity and drug delivery efficiency, PLGA nanoparticles of 300 nm may be the most promising candidate based on the results in this study.
Jun Liu (Advisor)
Ron Xu (Other)
Engineering
polymeric nanoparticle; ultrasonic enhancement; drug delivery

Recommended Citations

Citations

  • Li, J. (2010). Polymeric Nanoparticles for Ultrasonic Enhancement and Targeted Drug Delivery [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1280349038

    APA Style (7th edition)

  • Li, Jie. Polymeric Nanoparticles for Ultrasonic Enhancement and Targeted Drug Delivery. 2010. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1280349038.

    MLA Style (8th edition)

  • Li, Jie. "Polymeric Nanoparticles for Ultrasonic Enhancement and Targeted Drug Delivery." Master's thesis, Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1280349038

    Chicago Manual of Style (17th edition)

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© 2010, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.