2026-09-19T09:06:19Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/341582022-01-13T07:53:48Zcom_1721.1_7582com_1721.1_7581col_1721.1_131023
Ram Sasisekharan.
Eavarone, David A. (David Alan)
Massachusetts Institute of Technology. Biological Engineering Division.
Massachusetts Institute of Technology. Department of Biological Engineering
2006-09-28T15:12:57Z
2006-09-28T15:12:57Z
2004
2004
http://hdl.handle.net/1721.1/34158
69019122
Thesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2004.
Includes bibliographical references (leaves 36-38).
Anti-angiogenic therapy offers many benefits over traditional cytotoxic chemotherapy including fewer toxic side effects and the reduced development of drug resistance. Anti-angiogenics alone have not proven effective in inducing tumor regression in the clinic due to both the cytostatic nature of anti-angiogenic therapy and the potential formation of new regions of hypoxia within the tumor after therapy. The new therapeutic paradigm is for combining both anti-angiogenics and traditional cytotoxic agents for a synergistic effect. The efficacy of cytotoxic agents may be reduced after anti-angiogenic therapy, however, due to limited access to tumor vasculature and hypoxia-induced drug resistance. We propose that loading cytotoxic agents within the tumor prior to blood vessel collapse will enable both greater drug accumulation within the tumor as well as a reduction in the formation of therapy-induced regions of hypoxia. We present here a novel nanodelivery vehicle termed a 'nanocell' for the spatio-temporal recruitment of both anti-angiogenics and cytotoxic agents within the solid tumor to achieve this goal. Nanocells consist of a polymeric nanocore encapsulating the cytostatic agent doxorubicin surrounded by a lipid vesicle containing the anti-angiogenic agent combretastatin A4.
(cont.) Nanocell treatment resulted in an 88% reduction in tumor size in vivo, compared to a 66% reduction in tumor size after delivering combretastatin A4 lipid vesicles and doxorubicin nanocores simultaneously but separately. Nanocell treatment also resulted in a significant reduction in systemic toxicity, fewer metastases to the lung and liver, and a greater degree of tumor apoptosis.
by David A. Eavarone.
S.M.
38 leaves
1947467 bytes
1948947 bytes
application/pdf
application/pdf
eng
Massachusetts Institute of Technology
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http://dspace.mit.edu/handle/1721.1/7582
Biological Engineering Division.
A novel nanodelivery system for combination tumor therapy
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<Abstract>Anti-angiogenic therapy offers many benefits over traditional cytotoxic chemotherapy including fewer toxic side effects and the reduced development of drug resistance. Anti-angiogenics alone have not proven effective in inducing tumor regression in the clinic due to both the cytostatic nature of anti-angiogenic therapy and the potential formation of new regions of hypoxia within the tumor after therapy. The new therapeutic paradigm is for combining both anti-angiogenics and traditional cytotoxic agents for a synergistic effect. The efficacy of cytotoxic agents may be reduced after anti-angiogenic therapy, however, due to limited access to tumor vasculature and hypoxia-induced drug resistance. We propose that loading cytotoxic agents within the tumor prior to blood vessel collapse will enable both greater drug accumulation within the tumor as well as a reduction in the formation of therapy-induced regions of hypoxia. We present here a novel nanodelivery vehicle termed a 'nanocell' for the spatio-temporal recruitment of both anti-angiogenics and cytotoxic agents within the solid tumor to achieve this goal. Nanocells consist of a polymeric nanocore encapsulating the cytostatic agent doxorubicin surrounded by a lipid vesicle containing the anti-angiogenic agent combretastatin A4.</Abstract>
<Abstract>(cont.) Nanocell treatment resulted in an 88% reduction in tumor size in vivo, compared to a 66% reduction in tumor size after delivering combretastatin A4 lipid vesicles and doxorubicin nanocores simultaneously but separately. Nanocell treatment also resulted in a significant reduction in systemic toxicity, fewer metastases to the lung and liver, and a greater degree of tumor apoptosis.</Abstract>
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