The recently reported Frame Guided Assemblies (FGA) strategy has been successfully applied to prepare assemblies with designed shapes and sizes, which exhibit good stability, providing a potential platform for drug delivery. Herein to realize controllable drug release, this work has introduced the cleavable disulfide bond into the frame, which plays important roles in both guiding and supporting the formed assemblies. It has been demonstrated that upon stimuli, the FGA vesicles could be deformed to release the loaded molecules under physiological condition, demonstrating the importance of leading hydrophobic groups. Furthermore, the disassembly of 2D frame-guided assembly system has also been realized through the same method. These responsive FGA systems may provide new nano-vehicles for intracellular drug delivery which might benefit the design of responsive nanomaterials and controllable drug delivery systems.