Although charge-converting nanoparticles (NPs) potentially penetrate tumours deeply, conventional charge conversion strategies possess limitations, including low selectivity and slow, inconsistent conversion rate within the tumour microenvironment. In this study, we synthesized a zwitterionic near-infrared cyclodextrin derivative of heptamethine cyanine and complexed it with pheophorbide-conjugated ferrocene to produce multifunctional theranostic nanotherapeutics. Our NPs demonstrated enhanced tumour-targeting ability, enabling the highly specific imaging of rectal tumours, with tumour-to-rectum signal ratios reaching up to 7.8. The zwitterionic surface charge of the NPs was rapidly converted to a cationic charge within the tumours on 880 nm near-infrared laser irradiation, promoting the tumoural penetration of NPs via transcytosis. After penetration, photodynamic/chemodynamic therapy was initiated using a 660 nm laser. Our NPs eradicated clinically relevant-sized heterotopic tumours (~250 mm³) and orthotopic rectal tumours, displaying their potential as theranostic nanoplatforms for targeting rectal cancer.

尽管电荷转换纳米颗粒 （NPs） 可能会深入肿瘤，但传统的电荷转换策略具有局限性，包括低选择性和肿瘤微环境中缓慢、不一致的转化率。在这项研究中，我们合成了七甲嘧啶花青的两性离子近红外环糊精衍生物，并将其与萦戊比共轭二茂铁复合，生产多功能治疗诊断纳米治疗药物。我们的 NPs 表现出增强的肿瘤靶向能力，能够对直肠肿瘤进行高度特异性成像，肿瘤与直肠信号比高达 7.8。NPs 的两性离子表面电荷在 880 nm 近红外激光照射下迅速转化为肿瘤内的阳离子电荷，促进 NPs 通过转胞吞作用渗透到肿瘤中。穿透后，使用 660 nm 激光开始光动力/化学动力学治疗。我们的 NPs 根除了临床相关大小的异位肿瘤 （~250 mm³） 和原位直肠肿瘤，显示出它们作为靶向直肠癌的治疗诊断纳米平台的潜力。