A new design to synthesize thiol-responsive degradable polylactide (PLA)-based micelles having a disulfide linkage in the middle of triblock copolymers is reported. They were synthesized by a new method that centers on the use of a disulfide-labeled diol as an initiator for ring-opening polymerization, followed by controlled radical polymerization. These well-controlled copolymers with mono modal and narrow molecular weight distribution ((M) over bar (w)/(M) over bar (n) < 1.15) self-assembled to form aqueous micellar aggregates with disulfide-containing PLA cores, which is not toxic to cells. Central disulfide linkages were cleaved in response to thiols; such thiol-triggered degradation enhanced the release of encapsulated anticancer drugs.