Folate-conjugated pH-controllable fluorescent nanomicelles acting as tumor targetable drug carriers

The authors describe biocompatible nanomicelle based drug carriers that can be used for simultaneous (a) fluorescence tracking, (b) pH-controlled release of the cancer drug doxorubicin (DOX), and (c) targeting the folate receptor. The pH-sensitive triblock copolymer is composed of poly-2-(diisopropylamino) ethyl methacrylate and methoxypoly (ethylene glycol) which were prepared by radical polymerization and 'click' chemistry. The copolymers undergo self-assembly to form spherical micelles with diameters between 100 and 200 nm and a pH-trigger capability at pH values from 5.8 to 6.2. The micelles enabled DOX to be released at pH 5.0 at a much higher rate than at pH 7.4. Studies on cellular uptake revealed selective internalization of the DOX-loaded nanomicelles into HeLa cells where they can be imaged fluorometrically. Quantitative analysis of the green fluorescence indicated that the FITC-labeled micelles possess a transfection efficiency of about 79% while that of the nanomicellles with folate is only ∼40% under the same conditions. Confocal laser scanning microscopy indicates that the micelles invade the lysosome of HeLa cells and that the DOX released by micelles causes strong cell lethality. In our preception, this work provides useful insights in terms of designing multifunctional drug carriers and of improving the applicability of copolymer micelles for drug delivery systems. .