The first example of simple nanoaggregates, self-assembled from a new class of polymer has been explored. The synthesis and characterization of polyethylene glycol and doxorubicin attached to a 1,6-heptadiyne derivative (Macromonomer) are clearly described. Macromonomer is polymerized via olefin metathesis living cyclopolymerization method using the Grubbs-Hoveyda catalyst to produce a water-soluble Dox-Peg-Rcp-Fmoc polymer. All of the monomers and polymers are carefully characterized by GPC and 1H NMR spectroscopy. Fmoc deprotection of the Dox-Peg-Rcp-Fmoc polymer is carried out to produce the Dox-Peg-Rcp polymer. The newly designed Dox-Peg-Rcp polymer shows nanoaggregation in water. In addition to that, they are soluble in water as well as biological media. The drug release profile at mild acidic condition shows the importance of having ester linker. CLSM images of Dox-Peg-Rcp nanoaggregates clearly show the efficient internalization into the living cells. MTT assays of Dox-Peg-Rcp nanoaggregates show that these nanoaggregates have a greater anticancer efficacy. To the best of our knowledge, this is the first report on water-soluble polyacetylenes for biological/drug delivery applications.
Keywords: Hoveyda-Grubbs catalyst; RCMP; doxorubicin; polyacetylenes; self-assembly.