A multifunctional nanoplatform, which generally integrates biosensing, imaging diagnosis, and therapeutic functions into a single nanoconstruct, has great important significance for biomedicine and nanoscience. Here, we developed a core–shell–shell multifunctional polydopamine (PDA) modified upconversion nanoplatform for intracellular tumor-related mRNAs detection and near-infrared (NIR) light triggered photodynamic and photothermal synergistic therapy (PDT–PTT). The nanoplatform was constructed by loading a silica shell on the hydrophobic upconversion nanoparticles (UCNPs) with hydrophilic photosensitizer methylene blue (MB) entrapped in it, and then modifying PDA shells through an in situ self-polymerization process, thus yielding a core–shell–shell nanoconstruct UCNP@SiO₂–MB@PDA. By taking advantages of preferential binding properties of PDA for single-stranded DNA over double-stranded DNA and the excellent quenching property of PDA, a UCNP@SiO₂–MB@PDA–hairpin DNA (hpDNA) nanoprobe was developed through adsorption of fluorescently labeled hpDNA on PDA shells for sensing intracellular tumor-related mRNAs and discriminating cancer cells from normal cells. In addition, the fluorescence resonance energy transfer from the upconversion fluorescence (UCF) emission at 655 nm of the UCNPs to the photosensitizer MB molecules could be employed for PDT. Moreover, due to the strong NIR absorption and high photothermal conversion efficiency of PDA, the UCF emission at 800 nm of the UCNPs could be used for PTT. We demonstrated that the UCNP@SiO₂–MB@PDA irradiated with NIR light had considerable PDT–PTT effect. These results revealed that the developed multifunctional nanoplatform provided promising applications in future oncotherapy by integrating cancer diagnosis and synergistic therapy.

中文翻译：

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核-壳-壳多功能纳米平台用于细胞内肿瘤相关mRNA成像和近红外光触发的光动力-光热协同治疗

多功能纳米平台通常将生物传感，影像诊断和治疗功能集成到单个纳米结构中，对生物医学和纳米科学具有重要意义。在这里，我们开发了一种核-壳-壳多功能聚多巴胺（PDA）修饰的上转换纳米平台，用于细胞内肿瘤相关mRNA的检测和近红外（NIR）光触发的光动力和光热协同疗法（PDT-PTT）。纳米平台的结构是，将二氧化硅壳装入疏水性上转换纳米颗粒（UCNP）中，并在其中包裹亲水性光敏剂亚甲基蓝（MB），然后通过原位自聚合过程修饰PDA壳，从而得到核-壳-壳纳米结构UCNP @ SiO ₂–MB @ PDA。通过利用PDA对单链DNA的优先结合特性优于双链DNA以及PDA的出色猝灭特性，通过吸附荧光标记法开发了UCNP @ SiO ₂ –MB @ PDA–发夹DNA（hpDNA）纳米探针。 PDA外壳上的hpDNA可感应细胞内肿瘤相关mRNA，并区分癌细胞与正常细胞。另外，从在655 nm的UCNP的上转换荧光（UCF）发射到光敏剂MB分子的荧光共振能量转移可用于PDT。此外，由于PDA的强NIR吸收和高的光热转换效率，UCNP在800 nm处的UCF发射可用于PTT。我们证明了UCNP @ SiO ₂用近红外光照射–MB @ PDA具有相当大的PDT–PTT效果。这些结果表明，开发的多功能纳米平台通过整合癌症诊断和协同治疗，在未来的肿瘤治疗中提供了有希望的应用。