A Dual-Functional Magnetic Nanoparticle for Rapid Extraction and Targeted Tumor Delivery of Tiancimycin

Abstract

Anthraquinone-fused enediynes (AFEs) are a class of microbial natural products with remarkable cytotoxicity and exhibit promising application prospects in tumor therapy. Taking tiancimycins (TNMs) as an example, this class of compounds holds great potential against triple-negative breast and liver cancers. However, the low production titers of AFEs in actinobacterial hosts make their enrichment and separation processes both cumbersome and costly. Therefore, the main objective of this study was to develop a rapid and reusable magnetic platform for TNM enrichment and recovery. Inspired by the pi-pi stacking interactions between AFEs and their natural binding proteins in the producing strains, this study designed and prepared alizarin- and folic acid-co-modified magnetic nanoparticles (PNMP-AZ-FA). On the one hand, these nanoparticles can directly and specifically adsorb TNMs from the crude extract of Streptomyces sp. CB03234-S, enabling efficient separation. On the other hand, the folic acid modification was explored as a proof-of-concept delivery element for drug-loaded nanoparticles in folate receptor (FR)-expressing tumor models. PNMP-AZ-FA showed loading capacities of 87.8 and 106.7 mg/g for TNM A and TNM D, respectively, and retained high adsorption performance during 20 repeated cycles. Animal experiment results demonstrated that the TNM-loaded nanoparticle (PNMP-AZ-FA@TNM A) improved antitumor activity under the tested conditions, especially in the FR-high KB model; however, receptor-dependent uptake, biodistribution, and pharmacokinetic validation are still required. In summary, this nanoparticle holds great application prospects in the rapid separation and acquisition of AFEs, while its tumor-delivery application should be regarded as preliminary evidence.