Several cross-linking strategies have been adopted in the drug delivery field to increase the stability of self-assembled nanostructures and introducing stimuli-responsive properties to the delivery system. The dynamic nature of self-assembled nanostructures can compromise their stability in biological environments due to the presence of other entities (e.g. proteins) and dilution upon injection in the body. This can lead to premature payload leakage. Stabilisation of amphiphilic assemblies by covalent bonds is a versatile method to address the above-mentioned challenges, whilst stimuli-responsive motifs can be incorporated simultaneously. A stimuli-responsive cross-linker domain that is cleaved in the presence of the desired stimuli allows triggered-structure disassembly and controlled payload delivery. Herein, we leveraged natural enzymes as triggers for cargo release due to their inherent involvement in disease progression. The functional alkyne handles, introduced into the copolymers as described above, were used as cross-linking points using azido-bifunctionalised peptides bearing a protease sensitive sequence. A model matrix metalloproteinase was selected as our initial target due to their involvement in many diseases. Matrix metalloproteinase 7 (MMP-7) was chosen due to its small size with a Mw of only 19 kDa in its active form, which allows sufficient penetration into the polymer network of the nanogels to cleave the cross-links.