Light cross-linkable and pH de-cross-linkable drug nanocarriers for intracellular drug delivery

Ideal drug delivery systems are required to be stable in circulation, while instable at targeted sites to induce rapid drug release. To address this dilemma, novel light cross-linkable and pH de-cross-linkable micelles were developed as drug nanocarriers. Poly(ethylene glycol)-poly-(hydrazone umbelliferone)-aspartamide (mPEG-OMC) with light responsive coumarin moieties and pH responsive hydrazone groups in the side chains was synthesized. The polymers can self-assemble into micelles, which can be conveniently stabilized via UV-light induced cross-linking based on the dimerization of coumarin moieties. While under slight acidic conditions, the cross-linked micelles can also be de-cross-linked by the cleavage of hydrozone bonds in the cross-linking segments, accelerating the release of encapsulated drugs. Thus the benefits of pH and light stimuli-responsiveness can be combined and their disadvantages are avoided. The doxorubicin-loaded micelles showed high mortality towards HepG2 cells. We have demonstrated the UV light cross-linkable micelles with pH-triggered de-cross-linking properties as a new approach for designing smart drug delivery systems.