The action of phospholipase A2 (PLA(2)) on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes (vesicles) - an integral component in the polymer enzyme liposome therapy (PELT) mechanism (R. Duncan et al., J. Controlled Release 2001, 74, 135) for the controlled delivery of poorly soluble therapeutic molecules within liposomes - may be "masked" by conjugation to the biodegradable polymer dextrin and subsequently regenerated by the endogenous enzyme alpha-amylase that degrades the dextrin; that is, incorporating the so-called polymer-unmasked-masked protein therapy (PUMPT) approach (R. Duncan, et al. Biomacromolecules 2008, 9, 1146). Small-angle neutron scattering (SANS) has been used to quantify the detailed structure of DPPC liposomes and any perturbation in that structure induced by the presence of PLA(2) in native, "masked" (dextrin-PLA(2) conjugate) and an in situ alpha-amylase-unmasked form. A time-dependent degradation of the vesicular structure was observed for the two active PLA(2) cases, but not for the masked case. This study demonstrates that the PLA(2)-induced hydrolysis of the DPPC - and the associated rupture of the liposome and the release of the enclosed material - may be controlled through masking with dextrin. Accordingly, the viability of using such a combinatorial nanomedicine approach as a general route for the controlled delivery of poorly soluble therapeutic molecules is shown.