We reported dual-fluorescent hydroxyapatite–doxorubicin (DOX) (DDHAP) nanocomposites for tumor-targeted therapy. A newly designed fluorescent tumor-targeting group, DFA₁, is grafted onto the nanoparticle surface, which can enhance the cellular uptake of DDHAP by binding to γ-glutamyl transpeptidase (GGT), a cell surface-associated enzyme that is overexpressed on cancer cell membranes. This DFA₁ moiety could undergo fluorescence quenching after binding to GGT, and the whole nanocomposite collapsed under the cancerous pH condition, thereby releasing the free fluorescent DOX as an effective anticancer drug. Thus, ratiometric fluorescence tracking can be built up by measuring the DOX/DFA₁ fluorescence ratio. The dual fluorescence for ratiometric real-time tracking of the nanotherapeutic agents provides a new platform for better understanding the detailed process of their cellular uptake and intracellular dissociation. Moreover, as confirmed by in vivo studies, hydroxyapatite–DOX nanotheranostic agents demonstrate specific tumor-targeting, efficient tumor tissue penetrating and excellent tumor inhibiting effects. Nanotheranostic agents based on DDHAP show high potential for effective cancer treatment in future clinical settings.

中文翻译：

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实时监测羟基磷灰石-阿霉素纳米治疗剂对按需肿瘤靶向化疗的作用†

我们报道了用于肿瘤靶向治疗的双荧光羟基磷灰石-阿霉素（DOX）（DDHAP）纳米复合材料。一种新设计的荧光靶向肿瘤基团DFA ₁被移植到纳米颗粒表面，它可以通过与γ-谷氨酰转肽酶（GGT）结合来增强DDHAP的细胞摄取，GGT是一种在癌细胞上过度表达的与细胞表面相关的酶膜。该DFA ₁部分在与GGT结合后可能会发生荧光猝灭，并且整个纳米复合物在癌性pH条件下会折叠，从而释放出游离的荧光DOX作为有效的抗癌药物。因此，可以通过测量DOX / DFA ₁建立比例荧光跟踪荧光比。用于比例实时跟踪纳米治疗剂的双重荧光提供了一个新平台，可以更好地了解其细胞摄取和细胞内解离的详细过程。此外，正如体内研究所证实的那样，羟基磷灰石– DOX纳米热能剂具有特异性靶向肿瘤，有效穿透肿瘤组织和出色的抑瘤作用。基于DDHAP的纳米治疗剂在未来的临床环境中显示出有效治疗癌症的巨大潜力。