Tan Baojin, Zhao Chao, Wang Jing, Tiemuer Aliya, Zhang Yuanyuan, Yu Hui, Liu Yi
Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, PR China.
Department of Biomedical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 211198, PR China.
Acta Biomater. 2023 Jan 1;155:554-563. doi: 10.1016/j.actbio.2022.08.078. Epub 2022 Sep 8.
The development of effective and safe tumor photothermal therapeutic strategies has attracted considerable attention. Herein, we synthesized tumor microenvironment (TME)-activatable self-assembling organic nanotheranostics (NRhD-PEG-X NPs (X = 1, 2, 3, and 4)) for precise tumor targeting and upconversion image-guided photothermal therapy (PTT). The amphiphilic polymer NRhD-PEG-X consisted of upconversion luminescent probes (NRhD) modified with polyethylene glycol (PEG) of various lengths. The continuous external irradiation-free photothermal NRhD-PEG-4 NPs with pKa 6.70 displayed high sensitivity and selectivity to protons, resulting in the turn-on upconversion luminescence and enhanced photothermal properties in the acidic TME without asynchronous therapy and side effects. This nanotheranostic offers acidic activatability, tumor targetability, and PTT enhancement, thus allowing autofluorescence-free upconversion luminescent imaging-guided precision PTT. Our strategy affords a paradigm to develop activatable theranostic nanoplatforms for precision medicine. STATEMENT OF SIGNIFICANCE: As a hyperthermia-based treatment, activatable photothermal therapy (PTT) is highly significant in tumor treatment. Herein, we develop acidic tumor microenvironment-activatable nanotheranostics for upconversion luminescent imaging-guided diagnosis and precision tumor-targeted PTT. PEGylation of upconversion dyes not only could self-assemble to yield organic nanoparticles in water, but it could also significantly improve biocompatibility, stability, and circulation time and tune significantly the pKa value of nanoparticles. In an acidic tumor microenvironment, NRhD-PEG-4 NPs with pKa 6.70 show high sensitivity to release NRhDH-PEG-4 NPs, which exhibit good upconversion luminescence and enhanced photothermal effect. Therefore, upconversion luminescence imaging-guided precision PTT has high potential to enhance cancer diagnostic and therapeutic efficiency.
有效且安全的肿瘤光热治疗策略的发展已引起了广泛关注。在此，我们合成了肿瘤微环境（TME）可激活的自组装有机纳米诊疗剂（NRhD-PEG-X纳米粒子（X = 1、2、3和4）），用于精确的肿瘤靶向和上转换成像引导的光热治疗（PTT）。两亲性聚合物NRhD-PEG-X由用不同长度的聚乙二醇（PEG）修饰的上转换发光探针（NRhD）组成。具有6.70的pKa值的连续无外部照射的光热NRhD-PEG-4纳米粒子对质子表现出高灵敏度和选择性，从而在酸性TME中产生开启式上转换发光并增强光热性能，而不会产生异步治疗和副作用。这种纳米诊疗剂具有酸性可激活性、肿瘤靶向性和PTT增强作用，从而实现无自发荧光的上转换发光成像引导的精确PTT。我们的策略为开发用于精准医学的可激活诊疗纳米平台提供了范例。意义声明：作为一种基于热疗的治疗方法，可激活光热治疗（PTT）在肿瘤治疗中具有重要意义。在此，我们开发了酸性肿瘤微环境可激活的纳米诊疗剂，用于上转换发光成像引导的诊断和精确的肿瘤靶向PTT。上转换染料的聚乙二醇化不仅可以在水中自组装产生有机纳米粒子，还可以显著提高生物相容性、稳定性和循环时间，并显著调节纳米粒子的pKa值。在酸性肿瘤微环境中，具有6.70的pKa值的NRhD-PEG-4纳米粒子对释放NRhDH-PEG-4纳米粒子表现出高灵敏度，后者表现出良好的上转换发光和增强的光热效应。因此，上转换发光成像引导的精确PTT具有提高癌症诊断和治疗效率的巨大潜力。
