Investigating transport of charged nanoparticles by multiphoton fluorescence correlation spectroscopy (MPFCS)

Nanoparticles have been demonstrated as a promising new generation of specific imaging agents and targeted delivery vehicles for the diagnosis and treatment of solid tumors. Nonetheless, for optimal therapy of tumors, the nanoparticles must penetrate the tumor interstitial matrix to reach the cancer cells. This thesis describes the development of a multiphoton fluorescence correlation spectroscopy (MPFCS) system and its utilization to probe the effect of charge on the diffusion of quantum dot (QD) nanocrystals in collagen and collagen-hyaluronan (HA) composite gel models of human colon adenocarcinoma (LS174T). The MPFCS system was integrated with a multiphoton laser-scanning microscope (MPLSM) to enable visualization of QD distribution and collagen organization, as well as diffusion measurements. QDs of three different charges by modifying the surface of pre-made CdSe/CdZnS QDs with dihydrolipoic acid (DHLA), DHLA-polyethyleneglycol (DHLA-PEG) and amino-functionalized DHLA-PEG (DHLA-PEG-NH2). Aggregation was observed in QD-DHLA (4-potential = -31.12 mV) and QD-DHLA-PEG-NH2 (4-potential = +37.39 mV) samples in gels, but the distribution of QD-DHLA-PEG (ý-potential = -18.16 mV) was uniform. FCS measurements were performed for each QD sample in both gel models. Experimental data indicated anomalous subdiffusion of QDs in both gels with all samples having the same time exponent. The transport coefficient of QD-DHLA-PEG was significantly higher than QD-DHLA and QD-DHLA-PEG-NH2. A two-component free diffusion model also provided a good fit for the data, but did not provide a clear picture on the role of charge in diffusion. Our experiments suggest that anionic and cationic nanoparticles experience more hindrance compared to neutral, PEGylated nanoparticles in both collagen and collagen-HA gels.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2007

Author dc:creator

• Poh, Ming-Zher

Advisor dc:contributor.advisor

• Rakesh K. Jain.

• Electrical Engineering and Computer Science.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/42256

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/42256