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Omega‐3 Fatty Acid Grafted PAMAM‐Paclitaxel Conjugate Exhibits Enhanced Anticancer Activity in Upper Gastrointestinal Cancer Cells
Author(s) -
Dichwalkar Tanmay,
Patel Shraddha,
Bapat Samhita,
Pancholi Priya,
Jasani Neel,
Desai Bina,
Yellepeddi Venkata K.,
Sehdev Vikas
Publication year - 2017
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201600457
Subject(s) - conjugate , paclitaxel , chemistry , omega 3 fatty acid , cancer cell , fatty acid , gastrointestinal cancer , cancer , biophysics , biochemistry , cancer research , medicine , biology , polyunsaturated fatty acid , docosahexaenoic acid , colorectal cancer , mathematical analysis , mathematics
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 bioavailability, reduced solubility, and dose‐dependent toxicity impede its therapeutic use. PAMAMG 4.0 ‐NH 2 ‐DHA is synthesized by linking amine‐terminated fourth‐generation poly(amidoamine) (PAMAMG 4.0 ‐NH 2 ) dendrimers with omega‐3 fatty acid docosahexaenoic acid (DHA). Next, PAMAMG 4.0 ‐NH 2 ‐DHA‐PTX (DHATX) and PAMAMG 4.0 ‐NH 2 ‐PTX (PAX) conjugates are synthesized by subsequent covalent binding of PTX with PAMAMG 4.0 ‐NH 2 ‐DHA and PAMAMG 4.0 ‐NH 2 , respectively. 1 H‐NMR and MALDI‐TOF analyses are performed to confirm conjugation of DHA to PAMAMG 4.0 ‐NH 2 and PTX to PAMAMG 4.0 ‐NH 2 ‐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.