通过调节细胞外 Ca2+ 浓度来增强肿瘤细胞粘附具有高度挑战性，并且有望实现抗转移。在此，开发了一种pH响应性共轭聚合物-钙复合纳米颗粒（PFV/CaCO3/PDA@PEG），用于基于钙介导的细胞粘附增强的抗转移和活性氧（ROS）触发的钙超载和光动力疗法（PDT）肿瘤的协同治疗。 PFV/CaCO3/PDA@PEG主要配备共轭聚芴-亚乙烯基(PFV-COOH)复合CaCO3纳米粒子，在肿瘤酸性微环境下可快速分解，有效释放Ca2+和光敏剂PFV-COOH 。高细胞外Ca2+浓度有利于两个相邻钙粘蛋白胞外域之间生成二聚体，从而大大增强细胞与细胞的粘附并抑制肿瘤转移。对高转移性肿瘤细胞4T1和MCF-7的抑制率分别为97%和87%。这种精心设计的纳米颗粒还有助于实现PDT、线粒体功能障碍和ROS触发的Ca2超载协同治疗。此外，PFV/CaCO3/PDA@PEG 对 4T1 肿瘤生长表现出优异的体内抑制作用，并通过静脉注射和瘤内注射模式显示出显着的抗转移作用。因此，这项研究为钙介导的肿瘤转移抑制提供了一种强有力的策略。

Strengthening tumor cellular adhesion through regulating the concentration of extracellular Ca2+ is highly challenging and promising for antimetastasis. Herein, a pH-responsive conjugated polymer-calcium composite nanoparticle (PFV/CaCO3/PDA@PEG) is developed for calcium-mediated cell adhesion enhancement-based antimetastasis and reactive oxygen species (ROS)-triggered calcium overload and photodynamic therapy (PDT) synergistic tumor treatment. PFV/CaCO3/PDA@PEG is mainly equipped with conjugated poly(fluorene-co-vinylene) (PFV-COOH)-composited CaCO3 nanoparticles, which can be rapidly decomposed under the tumor acidic microenvironment, effectively releasing Ca2+ and the photosensitizer PFV-COOH. The high extracellular Ca2+ concentration facilitates the generation of dimers between two adjacent cadherin ectodomains, which greatly enhances cell-cell adhesion and suppresses tumor metastasis. The inhibition rates are 97 and 87% for highly metastatic tumor cells 4T1 and MCF-7, respectively. Such a well-designed nanoparticle also contributes to realizing PDT, mitochondrial dysfunction, and ROS-triggered Ca2+ overload synergistic therapy. Furthermore, PFV/CaCO3/PDA@PEG displayed superior in vivo inhibition of 4T1 tumor growth and demonstrated a marked antimetastatic effect by both intravenous and intratumoral injection modes. Thus, this study provides a powerful strategy for calcium-mediated metastasis inhibition for tumor therapy.