Breast cancer is the most common one in women worldwide and doxorubicin (Dox) is one of the most commonly used and effective drugs for breast cancer treatment. Unfortunately, Dox-based chemotherapy faces irreversible cardiotoxicity and unsatisfactory therapy efficiency. It is desirable to devise Dox nanoformulations with less adverse effects and greater therapeutic efficacy for this cancer treatment. In this work, a multifunctional calcium phosphate nanoformulation (ICG-Dox/DNA@CaP) was developed by co-loading Dox/DNA complexes and indocyanine green (ICG) molecules for photothermal therapy (PTT)-enhanced chemotherapy. In this nanocomposite, using DNA as Dox carrier facilitated Dox loading into the CaP matrix, and significantly reduced Dox leakage as well as cytotoxicity in comparison with that of free Dox in physiological medium (pH 7.4). In specific, ICG-Dox/DNA@CaP only released Dox in a weakly acidic nuclease-containing environment, such as tumor microenvironment and endosome/lysosome. Moreover, Dox/DNA complexes exhibited synergistic interactions with ICG-based photothermal effect on tumor cell apoptosis in this ICG-Dox/DNA@CaP nanocomposite. This work has demonstrated a new strategy to combine FDA-approved therapeutics (Dox and ICG) in CaP-based nanomaterials for reduced cytotoxicity and enhanced therapeutic effect, and provided a new way to engineer CaP carriers as multifunctional delivery systems for clinical anti-cancer therapy.

乳腺癌是全世界女性中最常见的一种，阿霉素（Dox）是治疗乳腺癌最常用和有效的药物之一。不幸的是，基于Dox的化学疗法面临不可逆的心脏毒性和令人满意的治疗效率。期望设计出对于这种癌症治疗具有更少的副作用和更大的治疗功效的Dox纳米制剂。在这项工作中，通过共同装载Dox / DNA复合物和吲哚菁绿（ICG）分子开发了多功能磷酸钙纳米制剂（ICG-Dox / DNA @ CaP），用于光热疗法（PTT）增强化疗。在这种纳米复合材料中，与自由Dox在生理介质中（pH 7.4）相比，使用DNA作为Dox载体可促进Dox加载到CaP基质中，并显着减少Dox泄漏和细胞毒性。具体而言，ICG-Dox / DNA @ CaP仅在含有弱酸性核酸酶的环境（例如肿瘤微环境和内体/溶酶体）中释放Dox。而且，在该ICG-Dox / DNA @ CaP纳米复合物中，Dox / DNA复合物与基于ICG的光热效应对肿瘤细胞凋亡表现出协同相互作用。这项工作证明了将FDA批准的治疗剂（Dox和ICG）与基于CaP的纳米材料相结合的新策略，以减少细胞毒性并增强治疗效果，并提供了一种工程化CaP载体作为临床抗癌多功能递送系统的新方法。在这种ICG-Dox / DNA @ CaP纳米复合材料中，Dox / DNA复合物与基于ICG的光热效应对肿瘤细胞凋亡表现出协同相互作用。这项工作证明了将FDA批准的治疗剂（Dox和ICG）与基于CaP的纳米材料相结合的新策略，以减少细胞毒性并增强治疗效果，并提供了一种工程化CaP载体作为临床抗癌多功能递送系统的新方法。在这种ICG-Dox / DNA @ CaP纳米复合材料中，Dox / DNA复合物与基于ICG的光热效应对肿瘤细胞凋亡表现出协同相互作用。这项工作证明了将FDA批准的治疗剂（Dox和ICG）与基于CaP的纳米材料相结合的新策略，以减少细胞毒性并增强治疗效果，并提供了一种工程化CaP载体作为临床抗癌多功能递送系统的新方法。