Synthesis of Photo/Reactive Oxygen Species Dual-Stimuli Supramolecular Drug and Controlled Release

As one of the main approaches for treating cancer, chemotherapy is faced with an inevitable challenge. That is, most of the powerful antitumor drugs exhibit non-selective toxicity, poor water solubility and rapid clearance by the reticuloendothelial system (RES). These issues significantly complicate the formulation and dosing of these drugs. Avoiding the laborious methods of traditional chemical synthesis, scientists have recently considered supramolecular amphiphiles formed by noncovalent drivings forces as novel building blocks for constructing drug delivery systems. Host-guest interactions have been recognition as one of the most important classes of noncovalent interactions for inducing self-assembly because of their excellent properties, which include specific molecular recognition, reversibility, and precise size controll-ability. Introduces the sensitive components and cleavable linkages the host-guest blocks, the stimuli-responsive supramolecules is considered to be very important future direction. Reactive oxygen species (ROS), which mainly include hydrogen peroxide (H2O2)、 superoxide (O2•-) and hydroxy radical (•OH) widely exist in living organisms and play crucial roles in cell signaling pathways. The level of ROS in pathological regions, such as tumor cells and activated immune cells, can reach up to 100 × 10-6 M, 2 to 3 orders of magnitude higher than in normal cells. Herein, we designed a type of dual-stimuli supramolecules by connecting the light responsive hydrophobic drug dastinib (HONB-DAS) with the methoxy polyethylene glycol (MPEG) chain through redox-switchable inclusion complexation between the β-cyclodextrin (β-CD) and ferrocene (Fc) groups. The resulting micelles exhibited not only reversible self-assembly behavior but also tunable release the bonding drug and encapsulated molecules in response to the light/oxidant combinations of dual-stimuli. Using the MCF-7 breast cells, we examined the photo/ROS- sensitizing activity of the pretreated MPEG-Fc/β-CD-ONB-DAS and DOX-loaded MPEG-Fc/β-CD-ONB-DAS micelles for combination therapy.

Project ID:PC10907-1723
External Project ID:MOST109-2221-E182-055