OBJECTIVE To enhance the nuclear-targeting therapeutic efficacy of camptothecin (CPT), this study synthesized a novel polypeptide-based nano-delivery carrier (aCD33-KNSN) that possesses both CD33-targeting capability and nuclear localization function. With CPT as the model drug, a CPT/aCD33-KNSN nano-targeted delivery system was further constructed, which is intended for the targeted treatment of acute myeloid leukemia (AML).

METHODS Camptothecin-loaded aCD33-KNSN nanoparticles (CPT/aCD33-KNSN) were prepared via dialysis method, and their physicochemical properties were systematically characterized. Using Kasumi-1 cells as the in vitro model, multiple techniques including MTT assay, flow cytometry, and laser confocal microscopy were employed to investigate the cytotoxicity, cell death patterns, and cellular uptake efficiency of the nanoparticles. For the in vivo study, BALB/c mice bearing Kasumi-1 xenografts were used as the animal model. The in vivo distribution, anti-tumor activity, and in vivo safety of CPT/aCD33-KNSN were comprehensively evaluated by detecting drug concentrations in various organs, calculating tumor inhibition rates, and analyzing blood system indices as well as liver function parameters.

RESULTS The CPT/aCD33-KNSN nanoparticles exhibited a spherical morphology, with an average diameter of (96.4±7.8)nm. Additionally, the zeta potential of the nanoparticles was determined to be (28.5±4.6)mV. The entrapment efficiency and drug loading capacity of CPT/aCD33-KNSN were above 92.4% and 15.2%, respectively, and the nanoparticles showed a sustained drug release profile. Biodistribution and cellular uptake studies demonstrated that CPT/aCD33-KNSN was mainly distributed at the tumor site in Kasumi-1-bearing mice. Meanwhile, coumarin-6 (C6)-loaded aCD33-KNSN nanoparticles (C6/KNSN) were predominantly accumulated in the nucleus of Kasumi-1 cells. Cell apoptosis and antitumor activity assays indicated that CPT/aCD33-KNSN induced apoptosis of Kasumi-1 cells more significantly compared with free CPT. In vivo antitumor experiments showed that CPT/aCD33-KNSN inhibited tumor growth in Kasumi-1 tumor-bearing mice more effectively than free CPT, with significantly reduced toxicity.

CONCLUSION The CPT/aCD33-KNSN nanoparticle system can enhance the antitumor effect of the encapsulated drug and reduce tissue toxicity, which may be attributed to the targeting ability of aCD33 and the nuclear localization capacity of the nanoparticles. The development of this nano-drug delivery system provides a novel strategy for the clinical treatment of acute myeloid leukemia(AML).