A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self-Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA-MB-231 Human Breast Cancer Cells

Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71D3)‐based micelles effectively encapsulate the doxorubicin (DOX) with a high drug‐loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296D1) vesicles. DOX released from the resultant P71D3/DOX micelles is approximately 1.3‐fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71D3/DOX micelles also enhance drug potency in breast cancer MDA‐MB‐231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy‐dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect. The copolymers with pendant dendron P71D3/DOX micelles exhibit higher tumor cellular uptake than the P296D1/DOX vesicles. The nanocarriers in the lysosomes release doxorubicin (DOX), followed by DOX translocation into the nucleus to exert its cytotoxic effect. The P71D3/DOX micelles enhance the DOX potency by twofold in breast cancer MDA‐MB‐231 cells compared with free DOX and P296D1/DOX vesicles.