A 5-fluorouracil-loaded pH-responsive dendrimer nanocarrier for tumor targeting.

A novel long-circulating and pH-responsive dendrimer nanocarrier was prepared for delivering 5-fluorouracil (5-FU) to tumors through the targeting of nanoparticles to the low pH environment of tumors. The nanocarrier, poly(2-(N,N-diethylamino)ethyl methacrylate) with methoxy-poly(ethylene glycol)-poly(amidoamine) (PPD), had a core-shell structure with 4.0 G poly(amidoamine) (PAMAM) as the core and parallel poly(2-(N,N-diethylamino)ethyl methacrylate) (PDEA) chains and methoxy-poly(ethylene glycol) (mPEG) chains as the shell. The PDEA chain was pH-responsive, and the PEG chains led to long circulation in blood vessels to achieve tumor targeting. The sizes, drug encapsulation and release of PPD nanocarriers showed high pH-dependency due to the PDEA chains, as they were hydrophilic at pH 6.5 and hydrophobic at pH 7.4. The encapsulation efficiency of 5-FU in PPD nanocarriers was as high as 92.5% through the pH transition. The release of 5-FU from PPD nanocarriers was much faster at pH 6.5 than at pH 7.4. The 5-FU-loaded nanocarrier had a long half-life after intravenous administration in mice and showed high tumor targeting. This nanocarrier composite also showed enhanced anticancer effects. PPD is a promising nanocarrier of anticancer drugs with high encapsulation, tumor targeting and pH-responsive release in tumors.