Molecular structural transformation regulated dynamic disordering of supramolecular vesicles as pH-responsive drug...

The spontaneous release of drug payloads in the whole body always results in the compromised drug bioavailability and ultimate therapeutic efficacy. To achieve enhanced therapeutic efficacy and reduced side effects, pH-responsive targeted drug delivery systems have been studied due to their enhanced tumor accumulation and controllable maximum drug release feature. The present study described a co-assembly constructed by a pH responsive molecule (i.e., malachite green carbinol base (MG)) and liposome for highly efficient doxorubicin (DOX) release in tumor cells (MG-DOX⊂L). The structural transformation of MG effectively regulates the drug release profile in acidic environment. The pH-responsive sensitivity of co-assembly can be fine-tuned by altering the mixing ratios of building blocks with pH responders (i.e., MG molecules). MG-DOX⊂L was beneficial for the DOX release at pH5.0 and showed a higher cytotoxicity in KB cells owing to the pH-responsive drug release in acidic organelles following endocytosis pathway. In vivo tumor targetability and growth inhibition were evaluated in KB cell-xenografted nude mice. We have demonstrated that effective tumor growth inhibition in vivo is attributed to the synergistic contributions from highly efficient cellular entry and responsive intracellular release of DOX from MG-DOX⊂L.