Synthesis of cyclodextrin‐based temperature/enzyme‐responsive nanoparticles and application in antitumor drug delivery

• LCC/SA-β-CD nanoparticle (NP) were prepared and characterized. • The NPs has a temperature/enzyme responsiveness • The negative NPs (−2.46 mV) could loaded with anti-tumor drug. • The CSL-loaded NPs could release drug when stimulated by temperature and enzyme. • The CSL-loaded NPs has cytotoxic activity and cancer cell apoptosis similar to CSL. Nanocarrier systems including the lipid-based, silica nanoparticle (NP)-based, chitosan-based, cyclodextrin (CD)-based, and so forth were prepared based on the various stimulus containing redox, pH, temperature, enzymes, etc. The nanocarriers with dual stimuli-responsive properties can meet further practical and clinical applications due to their highly accurate and controllable response to the lesion site, good drug release effect, and weak side effects. Here, a temperature/enzyme-responsive nanocarrier was prepared based on seven-[6-(diaminodipropylamine)-6-deoxy] -β-CD (SA-β-CD) and lauroyl choline chloride (LCC). The SA-β-CD/LCC NPs showed trapping and releasing properties for the antitumor drug celastrol (CSL) in the synergy of the temperature/enzyme stimuli. Notably, the release rate of CSL-trapped NPs reached 94 %, which is a relatively high value in numerous drug delivery systems using CSL as a drug model. Furthermore, cytotoxicity and apoptosis tests suggested that CSL-trapped NPs exhibited similar activity to intact CSL on five tumor cells. The dual response nanocarriers may pave a possible way for effectively targeted releasing anti-cancer drugs.