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. To decrease the potential side effects of the quinoline alkaloid camptothecin (CPT) in the treatment of malignant tumors, a supramolecular drug delivery based on synthesized biotin-PEG-linked calix[4]arene (PDCA) has been successfully developed.