Cation-π Interaction-Mediated Tumour Drug Delivery for Deep Intratumoral Penetration and Treatment

摘要

The limited efficacy of deep tumor treatments has been considered the“Achilles’ heel” of anticancer therapy due to multiple biological barriers.Whether passive diffusion or active transport has difficulties completely overcomingthese obstacles. Herein, cation-π interactions are utilized to constructa tumor drug delivery system integrating the merits of both passive and activetransport mechanisms. A cation-π interaction bridged trimetallic supramoleculardrug complex (Cπ-TMSDC) is constructed based on a drug consistingof one cisplatin molecule linked by K~+ (Pt-COOK) and the other drug with aRu metal complex containing curcumin (Ru-Cur). The obtained Cπ-TMSDCfurther self-assembles into cation-π-based trimetallic supramolecular drugmicelles (Cπ-TMSDMs) with efficient and stable transportation in vivo dueto the strong cation-π interaction formed between K+ and the curcumin unitin the Cπ-TMSDC. In acidic tumor microenvironment, the cation-π interactionsmartly dissociates, facilitating the quick release of Pt-COOK outsideCπ-TMSDMs to rapidly infiltrate the outer cellular layers by passive diffusion.Meanwhile, the dissociated Ru-Cur from the core layer of the Cπ-TMSDMsform secondary self-assemblies to deeply penetrate inside the solid tumor.Therefore, this strategy results in an efficient tumor drug delivery platformwith enhanced deep intratumoral penetration, improved therapeutic effects,and reduced systemic toxicity to normal organs.