Targeted delivery system would be an interesting platform to enhance the
therapeutic effect and to reduce the side effects of anticancer drugs. In this study, we have developed
lactobionic acid (LA)-modified
chitosan-
stearic acid (CS-SA) (CSS-LA) to deliver
doxorubicin (DOX) to
hepatic cancer cells. The average particle size of CSS-LA/DOX was ∼100 nm with a high entrapment efficiency of >95%. Drug release studies showed that DOX release from pH-sensitive
micelles is significantly faster at pH 5.0 than at pH 7.4. The LA conjugated
micelles showed enhanced cellular uptake in HepG2 and BEL-7402
liver cancer cells than free
drug and unconjugated
micelles. Consistently, CSS-LA/DOX showed enhanced cell cytotoxicity in these two cell lines.
Annexin-V/FITC and PI based apoptosis assay showed that the number of living cells greatly reduced in this group with marked presence of necrotic and apoptotic cells. LA-conjugated carrier induced typical chromatic condensation of cells; membrane blebbing and apoptotic bodies began to appear. In vivo, CSS-LA/DOX showed an excellent
tumor regression profile with no toxic side effects. The active targeting moiety, long circulation profile, and EPR effect contributed to its superior anticancer effect in HepG2 based
tumor. Our results showed that polymeric
micelles conjugated with LA increased the therapeutic availability of DOX in the
liver cancer cell based solid
tumor without any toxic side effects. The active targeting
ligand conjugated nanoparticulate system could be a promising therapeutic strategy in the treatment of
hepatic cancers.