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In recent decades, a large number of targeting drug delivery systems have been designed and evaluated for cancer therapy. An important part of these studies is to monitor the subcellular fate of macromolecules. Fluorescence labeling technique was the most adopted method. However, it had the disadvantages of altening the properties of drugs as well as artifactual redistribution of fluorescent markers caused by fixation. In the present study, a more accurate method, HPLC analysis preceded by subcellular fractionation was developed and validated to study the distribution of a newly synthesized tumor cell targeting drug delivery system, HPMA copolymer-5-FU conjugates (P-FU) in PC-3 cells. P-FU was proved to accumulate more in nuclei than free 5-FU, whose concentration in the culture medium was approximately 1/20 that of 5-FU when attaining similar nucleus drug concentration. On the contrary, the overwhelming majority of drugs accumulated in nonnucleus when PC-3 cells were treated with free 5-FU. These results indicated that P-FU had nuclear targeting effect. The developed procedure allows an accurate subcellular fate screening for many macromolecules.

Nuclear Targeting Study of HPMA Copolymer-5-Fluorouracil Conjugate Based on the Subcellular Distribution in PC-3 Cells