Temperature- and pH-controlled encapsulation and release of guest molecules from invertible carriers

Abstract A multi-stimuli-responsive copolymer consisting of a thermoresponsive block and a thermo- and pH responsive block forms different types of self-assemblies in aqueous solution. These self-assembled structures may be inverted by varying temperature and pH and may be used for controlled loading and release of both hydrophobic and hydrophilic guest molecules. This polymer forms vesicles in water at neutral pH (pH 7) above the body temperature (37 °C), which are capable of inverting their core and corona to produce micelles when the pH increases to 10 and temperature decreases to room temperature (25 °C). We used pyrene and 8-hydroxylpyrene-1,3,6-trisulfonic acid trisodium salt (HPTS) to probe the hydrophobic and hydrophilic microenvironments formed by the copolymer in response to changing temperature and pH. At pH 7 and 37 °C, the vesicles can entrap pyrene in their membrane and HPTS in their hydrophilic hollow cavity; at pH 10 and 25 °C, the micelles formed can encapsulate pyrene. Cooling the solution to 25 °C and adjusting the pH to 7 result in the release of the molecular probes from both the vesicles and the micelles. Formation of invertible micelles and vesicles in aqueous solutions allows for encapsulating delicate biomolecules which may be sensitive to the media of normal vesicles.