Targetable biodegradable nanoparticles for delivery of chemotherapeutic and imaging agents to ovarian cancer

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Title: Targetable biodegradable nanoparticles for delivery of chemotherapeutic and imaging agents to ovarian cancer
Author: Betancourt, Tania, 1981-
Abstract: Every year more than 10 million people develop cancers globally . Ovarian cancer , specifically , results in more than 22 ,000 new cases and 16 ,000 deaths from this disease yearly , more than any other cancer of the female reproductive system . In addition , because of non -specific symptoms and poor screening techniques , most ovarian cancer cases are discovered after the disease is in an advanced state . Consequently , aggressive and effective treatment options that incur minimal toxic effects to healthy tissue are in great need . In the present research , stealth biodegradable nanoparticles were developed as vehicles for the controlled and targeted delivery of chemotherapeutic agents for the treatment of ovarian cancer . The design of this delivery system consisted of nanoparticles of biodegradable polymers of the poly (lactic -co -glycolic acid ) family loaded with the chemotherapeutic agent doxorubicin or the imaging agents rhodamine 6G , indocyanine green or gadopentetic acid . Nanoparticles were modified by incorporation of functional poly (ethylene glycol ) on their surface to improve the stability of the colloidal suspension , increase their circulation lifetime in vivo , and provide a site for conjugation of targeting agents specific to ovarian tissue . Various methods were evaluated for this surface modification , including the use of polymer blends , the chemical conjugation of the polymers , and the polymerization of lactide and glycolide monomers initiated by heterofunctional poly (ethylene glycol ) . Nanoparticles incorporating poly (ethylene glycol ) presented improved characteristics compared to unmodified particles including smaller size , higher stability and slower release of the chemotherapeutic agent doxorubicin The actual drug or agent content was decreased in the case of doxorubicin and rhodamine , but increased for indocyanine green as a result of improved agent -polymer interactions . Poly (ethylene glycol ) -containing nanoparticles were conjugated to monoclonal antibody mAb106 -105 , which is specific to the extracellular domain of human folliclestimulating hormone (FSH ) receptors . These receptors are only expressed in ovarian cells in women , thus providing a system that is highly specific to ovarian tissue . The interaction and therapeutic potential of nanoparticles with or without targeting antibodies were tested on OVCAR -3 , Caov -3 , and MDA -MB -231 cancer cells .
URI: http : / /hdl .handle .net /2152 /3547
Date: 2008-08-28

Citation

Targetable biodegradable nanoparticles for delivery of chemotherapeutic and imaging agents to ovarian cancer. Doctoral dissertation, The University of Texas at Austin. Available electronically from http : / /hdl .handle .net /2152 /3547 .

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