Doxorubicin release is not a prerequisite for the in vitro cytotoxicity of HPMA-based pharmaceuticals: In vitro effect of extra drug-free GlyPheLeuGly sequences
2008
Abstract
A polymer–drug conjugate containing doxorubicin (DOX) bound to HPMA copolymer backbone through the enzymaticaly non-cleavable sequence GlyGly shows lower but significant cytotoxicity in vitro in seven cancer cell lines of mouse (EL4, 38C13, 3T3, BCL1) and human (SW620, Raji, Jurkat) origin if compared to conjugate bearing doxorubicin (DOX) bound to through GlyPheLeuGly sequence. The low cytotoxicity of GlyGly conjugate can be considerably increased by the presence of additional drug-free GlyPheLeuGly side chains.
The presence of the GlyPheLeuGly sequence in the conjugate structure increases its rate of intracellular accumulation. Normal cells (Balb/c splenocytes) accumulate less polymer–doxorubicin conjugate compared to cancer cells.