科研之友
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摘要
Solid tumors generally exhibit an acidic microenvironment which has been recognized as a potential route to distinguishing tumor from normal tissue for purposes of drug delivery or imaging. To this end we describe a pH and temperature sensitive polymeric adhesive that can be derivatized to carry drugs or other agents and can be tuned synthetically to bind to tumor cells at pH 6.8 but not at pH 7.4 at 37 degrees C. The adhesive is based on the universal reaction between membrane phosphatidyl choline (PC) molecules and polymers derivatized with multiple copies of the inverse motif, choline phosphate (CP). The polymer family we use is a linear copolymer of a CP terminated tetraethoxymethacrylate and dimethylaminoethyl (DMAE) methacrylate, the latter providing pH sensitivity. The copolymer exhibits a lower critical solution temperature (LCST) just below 37 degrees C when the DMAE is uncharged at pH 7.4 but the LCST does not occur when the group is charged at pH 6.8 due to the ionization hydrophilicity. At 37 degrees C the polymer binds strongly to mammalian cells at pH 6.8 but does not bind at pH 7.4, potentially targeting tumor cells existing in an acidic microenvironment. We show the binding is strong, reversible if the pH is raised and is followed rapidly by cellular uptake of the fluorescently labeled material. Drug delivery utilizing this dually responsive family of polymers should provide a basis for targeting tumor cells with minimal side reactions against untransformed counterparts.
- 出版日期2014-1
