Camptothecin-loaded supramolecular nanodelivery system based on amphiphilic calix[4]arene for targeted tumor therapy

Given the high toxicity and low bioactivity of the quinoline alkaloid camptothecin (CPT) in the treatment of malignant tumors, a more effective strategy is needed. One such strategy is the use of supramolecular nanocarriers to transport CPT to a therapeutic target, as a means to decrease potential side effects and enhance the therapeutic effect. Herein, biotin–PEG-linked calix[4]arene (PDCA) derived from our previously synthesized 5,11-dinitro calix[4]arene (NDCA) was successfully developed to transport CPT through the co-assembly of CPT@PDCA micelles. The formed CPT@PDCA micelles possessed a high encapsulation efficiency of 74.43 ± 0.41%. The in vitro release behavior of CPT from the PDCA micelles displayed a pH-responsive characteristic. Cytotoxicity measurements of the CPT-loaded PDCA in normal HUVEC cell lines and 4T1 cancer cell lines showed a drastic decrease in the toxicity to normal cells and an almost equivalent inhibitory effect on tumor proliferation compared with CPT alone. The loading of CPT in the calix[4]arene-based supramolecular delivery system exhibited excellent antitumor efficacy by inducing tumor cell apoptosis.