Polymer-based drug delivery systems may significantly improve cancer therapy. We developed amphiphilic poly(ε-caprolactone)-graft-(poly-N-(2-hydroxypropyl) methacrylamide) copolymers (PCL-graftpHPMA) with tunable amphiphilicity intended for efficient dual delivery via simultaneous encapsulation of hydrophobic drug, Bcl-2 inhibitor ABT-199, and pH-sensitive conjugation of other chemotherapeutics, doxorubicin, to desired sites, e.g. tumors. Using controlled RAFT polymerization and click chemistry welldefined PCL-graft-pHPMA of diverse Mw and physical properties were prepared. By simple dissolution they self-assembled into highly stable micelles with Dh ≈ 25 nm and low critical micelle concentration (around 5 μg mL−1). The total drug payload reached 17 wt% while maintaining system solubility. The micelles exhibited long-term stability in buffers, while they were cleaved in the presence of lipase, thus proving degradation and drug release after uptake to lysosomes of cancer cells with minimal drug leakage during blood circulation. PCL-graft-pHPMA micelles may serve as a long-circulating drug depo for effective dual therapy of diverse malignancies.