ABSTRACT

Optimised drug delivery systems with low toxicity and high efficacy for suppressing cancer cells are urgently needed. In this study, a quinolone derivative-based organoplatinum(II) supramolecular coordination complex (SCC) was synthesised by [2 + 2] coordination-driven self-assembly. Using this molecular design, synergistic chemotherapeutic effects were achieved by combining the anticancer agent platinum acceptor and quinolone derivative at a fixed ratio. Importantly, the well-defined rhomboidal shape and size of the SCC metallacycle self-assembled into nanoparticles with an average diameter of 38 nm in aqueous solution, conferring improved passive targeting and internalisation abilities towards tumour cells via the enhanced permeability and retention effect. In vitro evaluation with HepG2 cells showed that integration of the quinolone derivative and organoplatinum(II) acceptor improved antitumor activity compared with each independent component. These properties reveal the potential of Pt(II)-based SCCs for use in antitumor applications as a supramolecular chemotherapy self-delivery platform.

A Pt(II) metallacycle-based supramolecular self-delivery nanocarrier platform through coordination-driven self-assembly of a dipyridine-functionalised quinolone derivative donor (QD) and 60° Pt (II) acceptor (PhenPt) was successfully constructed. This nanocarrier considerably enhanced the internalisation and anticancer efficacy, as shown by in vitro studies.

摘要

迫切需要具有低毒性和高效抑制癌细胞作用的优化药物输送系统。在这项研究中，通过[2 + 2]配位驱动的自组装合成了基于喹诺酮衍生物的有机铂（II）超分子配位化合物（SCC）。使用这种分子设计，通过以固定比例组合抗癌药铂受体和喹诺酮衍生物，可获得协同的化学治疗效果。重要的是，明确定义的SCC金属环的菱形形状和大小可自组装成水溶液中平均直径为38 nm的纳米粒子，从而通过增强的渗透性和保留作用赋予肿瘤细胞更高的被动靶向和内化能力。体外用HepG2细胞进行的评估显示，与每个独立组分相比，喹诺酮衍生物和有机铂（II）受体的整合改善了抗肿瘤活性。这些特性揭示了基于Pt（II）的SCC作为超分子化学自传递平台在抗肿瘤应用中的潜力。

通过二吡啶功能化的喹诺酮衍生物供体（QD）和60°Pt（II）受体（PhenPt）的配位驱动自组装，成功构建了基于Pt（II）金属环的超分子自传递纳米载体平台。如体外研究所示，这种纳米载体大大增强了内在化和抗癌功效。