A novel gene transfection vector was fabricated based on the conjugation of
human serum albumin (HSA) and
maleimide end functionalized poly[(N,N-dimethylamino) ethyl
methacrylate] (
PDMAEMA). The bioconjugation was achieved in a site-specific manner to yield well-defined
polymer-
protein conjugates. The biohybrid was able to bind
DNA with high affinity resulting in nanoparticles with a HSA shell. This paper mainly focuses on the influence of polymeric chain length on the particle properties and their
drug-carrying ability to deliver
oligonucleotides into
breast cancer cells. The
cytotoxic agent of interest,
ISIS5132, is an
oligonucleotide which disrupts
DNA function within the cell. There was no evidence that the polymeric chain length had any effects on the conjugation efficiency and the subsequent condensation ability of the conjugates to
oligonucleotide. However, the polymeric chain length had an obvious effect on the size of the complex
micelles. Low molecular weights only led to loosely compacted complexes with the
oligonucleotide, while large molecular weight led to well-defined nanoparticle structures. More importantly, it was found that the variation in the length of the
PDMAEMA block resulted in a change in cytotoxicity of the
drug loaded complex
micelle. That is, the concentration of 50% inhibition (IC50 ) of the complex
micelle on MDA-MB-231 and MCF-7 cells reached the lowest value at a chain length of around 21 000 g mol(-1) . The IC50 value increased when the polymeric chain length was shorter (8000 g mol(-1) and 10 000 g mol(-1) ) while it increased again when PDMAMEA of M¯n = 47 000 g mol(-1) , probably due to insufficient release of the
drug. These result were reflected when investigating the performance of the polyplex using MCF-7 multicellular
tumor spheroids, where again the medium
PDMAEMA chain length led to the best delivery vehicle for
ISIS5132.