Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer Export

@article{citeulike:230880, abstract = {Prior studies suggested that nanoparticle drug delivery might improve the therapeutic response to anticancer drugs and allow the simultaneous monitoring of drug uptake by tumors. We employed modified PAMAM dendritic polymers <5 nm in diameter as carriers. Acetylated dendrimers were conjugated to folic acid as a targeting agent and then coupled to either methotrexate or tritium and either fluorescein or 6-carboxytetramethylrhodamine. These conjugates were injected i.v. into immunodeficient mice bearing human KB tumors that overexpress the folic acid receptor. In contrast to nontargeted polymer, folate-conjugated nanoparticles concentrated in the tumor and liver tissue over 4 days after administration. The tumor tissue localization of the folate-targeted polymer could be attenuated by prior i.v. injection of free folic acid. Confocal microscopy confirmed the internalization of the drug conjugates into the tumor cells. Targeting methotrexate increased its antitumor activity and markedly decreased its toxicity, allowing therapeutic responses not possible with a free drug. 10.1158/0008-5472.CAN-04-3921}, address = {University of Michigan Center for Biologic Nanotechnology and Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan.}, author = {Kukowska-Latallo, Jolanta F. and Candido, Kimberly A. and Cao, Zhengyi and Nigavekar, Shraddha S. and Majoros, Istvan J. and Thomas, Thommey P. and Balogh, Lajos P. and Khan, Mohamed K. and Baker, James R.}, citeulike-article-id = {230880}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-04-3921}, citeulike-linkout-1 = {http://cancerres.aacrjournals.org/content/65/12/5317.abstract}, citeulike-linkout-2 = {http://cancerres.aacrjournals.org/content/65/12/5317.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/15958579}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=15958579}, day = {15}, doi = {10.1158/0008-5472.CAN-04-3921}, issn = {0008-5472}, journal = {Cancer Res}, keywords = {dendrimer}, month = {June}, number = {12}, pages = {5317--5324}, posted-at = {2007-10-23 06:52:29}, priority = {2}, title = {Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-04-3921}, volume = {65}, year = {2005} }

TY - JOUR ID - citeulike:230880 L3 - citeulike-article-id:230880 N2 - Prior studies suggested that nanoparticle drug delivery might improve the therapeutic response to anticancer drugs and allow the simultaneous monitoring of drug uptake by tumors. We employed modified PAMAM dendritic polymers <5 nm in diameter as carriers. Acetylated dendrimers were conjugated to folic acid as a targeting agent and then coupled to either methotrexate or tritium and either fluorescein or 6-carboxytetramethylrhodamine. These conjugates were injected i.v. into immunodeficient mice bearing human KB tumors that overexpress the folic acid receptor. In contrast to nontargeted polymer, folate-conjugated nanoparticles concentrated in the tumor and liver tissue over 4 days after administration. The tumor tissue localization of the folate-targeted polymer could be attenuated by prior i.v. injection of free folic acid. Confocal microscopy confirmed the internalization of the drug conjugates into the tumor cells. Targeting methotrexate increased its antitumor activity and markedly decreased its toxicity, allowing therapeutic responses not possible with a free drug. 10.1158/0008-5472.CAN-04-3921 IS - 12 JF - Cancer Res SN - 0008-5472 AD - University of Michigan Center for Biologic Nanotechnology and Department of Radiation Oncology, University of Michigan Health System, Ann Arbor, Michigan. EP - 5324 TI - Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer VL - 65 SP - 5317 KW - dendrimer AU - Kukowska-Latallo, Jolanta AU - Candido, Kimberly AU - Cao, Zhengyi AU - Nigavekar, Shraddha AU - Majoros, Istvan AU - Thomas, Thommey AU - Balogh, Lajos AU - Khan, Mohamed AU - Baker, James PY - 2005/06/15/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-04-3921 ER -