In vitro evaluation of cytotoxicity and cellular uptake of alternating copolymers for use as drug delivery vehicles

Cancer is the collective group of diseases distinguished by uninhibited growth and spread of abnormal cells. It often results in death if the spread is not controlled. Most cancers are treated by surgery, radiation, chemotherapy, hormones, or immunotherapy. However, currently there are many issues with these forms of treatment, namely the lack of ability to consistently remove the entire tumor and the side effect of killing normal cells during the treatment process. Therefore there has been an increased interest in targeted drug delivery to tumors to specifically kill cancer cells. We have developed a highly adaptable amphiphilic alternating copolymer system that self-assembles into micelles for therapeutic delivery applications in cancer. The synthetic scheme includes the enzymatic polymerization of multifunctional linker molecules (dimethyl 5-hydroxyisopthalate) with poly(ethylene glycol). This chemoenzymatic synthesis is much faster and more convenient than an entirely chemical synthesis. Subsequent synthetic steps have been developed to attach ligands (for targeting), perfluorocarbons (19F MR imaging), fluorescent dyes (NIRF imaging), and radioiodine (nuclear imaging and radioimmunotherapy) to the backbone. Attachment of hydrocarbon or perfluorocarbon sidechains provides amphiphilicity to produce the multimodal self-assembling micelles. Additionally, encapsulation procedures for chemotherapeutic agents, doxorubicin and paclitaxel, have been established.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemical Engineering.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Miller, Michelle Teresa

Advisor dc:contributor.advisor

• Clark K. Colton.

• Chemical Engineering.

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/1721.1/51673

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/51673