Modification of the thermo-responsive behavior of polymeric micelles for specific drug delivery functions was investigated using combinations of micellar inner cores and outer shell polymer chemistries. Polymeric micelles comprised of AB block copolymers of PIPAAm (poly(N-isopropylacrylamide)) with either PBMA (poly(butyl methacrylate)) or PSt (polystyrene) were employed. PIPAAm-PBMA and PIPAAm-PSt block copolymers formed a core-shell micellar structure after dialysis of the block copolymer solutions in organic solvents against water at 20 degrees C. The hydrophobic drug, adriamycin, (ADR) was loaded into the inner core of the polymeric micelles by dialysis. The polymers showed reversible intermicellar dispersion/aggregation in response to temperature cycles through an outer polymer shell lower critical solution temperature (LCST for PIPAAm=32.5 degrees C), observed by DLS (dynamic light scattering) and transmittance measurements. Upon heating above the LCST, PIPAAm-PBMA micelles exhibited an abrupt increase in micropolarity and an abrupt decrease in microrigidity sensed by pyrene and 1, 3-bis(1-pyrenyl)propane (PC(3)P), respectively. In contrast, PIPAAm-PSt micelles maintained constant values with lower micropolarity and higher microrigidity than those of PIPAAm-PBMA micelles over the temperature range 20 to 40 degrees C. From these results, structural deformations produced by outer shell polymer structural change with temperature cycles through the LCST are proposed for the PBMA core possessing a lower T(g) (ca. 20 degrees C) than the outer shell PIPAAm LCST. The PSt core with a much higher T(g) (ca. 100 degrees C) than the outer shell LCST retained its structure, regardless of outer shell changes. PIPAAm-PBMA micelles released ADR only when heated above the LCST, while PIPAAm-PSt micelles did not. Cell cultures treated with PIPAAm-PBMA micelles loaded with ADR showed high in vitro cytotoxicity when heated above the LCST, while PIPAAm-PSt micelles loaded with ADR expressed very low in vitro cytotoxicity irrespective of temperature change through the LCST. The nature of hydrophobic segments comprising the micelle inner core offers an important control point for thermo-responsive drug release and the drug activity of the thermo-responsive polymeric micelle.