Journal
MACROMOLECULAR BIOSCIENCE
Volume 17, Issue 8, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201600457
Keywords
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Funding
- American Association of College of Pharmacy-New Investigator Award (AACP-NIA)
- Division of Pharm. Sciences, Arnold & Marie Schwartz College of Pharmacy & Health Sciences, Long Island Univresity
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Upper Gastrointestinal Cancers (UGCs) are a leading cause of cancer-related deaths worldwide. Paclitaxel (PTX) is frequently used for the treatment of UGCs; however, low bio-availability, reduced solubility, and dose-dependent toxicity impede its therapeutic use. PAMAMG(4.0)-NH2-DHA is synthesized by linking amine-terminated fourth-generation poly(amidoamine) (PAMAMG(4.0)-NH2) dendrimers with omega-3 fatty acid docosahexaenoic acid (DHA). Next, PAMAMG(4.0)-NH2-DHA-PTX (DHATX) and PAMAMG(4.0)-NH2-PTX (PAX) conjugates are synthesized by subsequent covalent binding of PTX with PAMAMG(4.0)-NH(2)DHA and PAMAMG(4.0)-NH2, respectively. H-1-NMR and MALDI-TOF analyses are performed to confirm conjugation of DHA to PAMAMG(4.0)-NH2 and PTX to PAMAMG(4.0)-NH2-DHA. The cell viability, clonogenic cell survival, and flow cytometry analyses are used to determine the anticancer activity of PTX, PAX, and DHATX in UGC cell lines. The in vitro data indicate that treatment with DHATX is significantly more potent than PTX or PAX at inhibiting cellular proliferation, suppressing long-term survival, and inducing cell death in UGC cells.
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