This processes permitted high DOX concentrations in the cytosol and its target site of the nucleus, thus increasing DOX potency in various wild and multidrug resistant (MDR) cell lines (3.8–8.8 times lower IC 50 than free DOX, depending on cell line). The ionization process of the block copolymers and ionized polymers assisted in disrupting the endosomal membrane. The micelle core was engineered for disintegration in early endosomal pH of tumor cells, quickly releasing DOX. The micelle surface hides TAT during circulation, which has the strong capability to translocate the micelle into cells, and exposes TAT at a slightly acidic tumor extracellular pH to facilitate the internalization process. The micelle formed via the dialysis method was approximately 95 nm in diameter and contained 15 wt.% of doxorubicin (DOX) by weight. As an alternative to cell specific cancer targeting strategies (which are often afflicted with the heterogeneity of cancer cells as with most biological systems), a novel polymeric micelle constitute of two block copolymers of poly(L-lactic acid)- b-poly(ethylene glycol)- b-poly(L-histidine)-TAT (transactivator of transcription) and poly(L-histidine)- b-poly(ethylene glycol) was developed.
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