Large-size-induced long-term retention in the body has hampered the translational applications of many reported nanomedicines. Herein, we reported a multifunctional theranostic agent composed of ultrasmall poly(acrylic acid)-functionalized Ni_0.85Se nanoparticles (PAA–Ni_0.85Se NPs), which were successfully obtained through a facile ambient aqueous precipitation strategy. Without exhibiting any noticeable toxicity, the as-prepared PAA–Ni_0.85Se NPs (average diameter of 6.40 ± 1.89 nm) showed considerable absorption in near-infrared (NIR) region and high photothermal conversion efficiency of 54.06%, which could induce remarkable photoacoustic signals for tumor imaging and heat for localized ablation of cancerous cells upon exposure to NIR light. Notably, the ultrasmall PAA–Ni_0.85Se NPs, unlike conventional nanomaterials with larger sizes, showed reasonable body clearance within 8 h after intravenous injection. Furthermore, ascribed to protonation process of amino groups in DOX molecules and carboxyl groups in PAA molecules in an acidic microenvironment, the drug-loaded (doxorubicin hydrochloride, DOX·HCl) PAA–Ni_0.85Se NPs (PAA–Ni_0.85Se–DOX NPs) revealed promoted drug release at acidic pH, which could be useful for acidic tumor microenvironment responsive drug delivery. Evident from the results of cell-killing assay in vitro and tumor treatment study in vivo, PAA–Ni_0.85Se–DOX NPs exhibited evident synergistic effects on killing 4T1 breast cancer cells. Thus, this study presents a multifunctional theranostic agent composed of ultrasmall PAA–Ni_0.85Se NPs for potential cancer treatment without long-term toxicity concerns.

中文翻译：

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无水光声成像和光热化学联合疗法的超小型Ni _0.85 Se纳米粒子的环境水合成

大尺寸诱导的在体内的长期保留阻碍了许多报道的纳米药物的翻译应用。在本文中，我们报道了一种由超小型聚丙烯酸官能化的Ni _0.85 Se纳米粒子（PAA–Ni _0.85 Se NPs）组成的多功能治疗剂，它是通过一种简便的环境水沉淀策略成功获得的。制备的PAA–Ni _0.85不会表现出任何明显的毒性。Se NPs（平均直径为6.40±1.89 nm）在近红外（NIR）区域显示出相当大的吸收率，并具有5​​4.06％的高光热转换效率，可在暴露时诱导显着的光声信号用于肿瘤成像并产生热，从而局部消融癌细胞近红外灯。值得注意的是，与较大尺寸的常规纳米材料不同，超小PAA–Ni _0.85 Se NPs在静脉注射后8 h内显示出合理的体内清除率。此外，归因于酸性微环境中DOX分子中的氨基和PAA分子中的羧基的质子化过程，载药量（盐酸阿霉素，DOX·HCl）为PAA-Ni _0.85 Se NPs（PAA-Ni _0.85Se–DOX NPs）显示在酸性pH下药物释放促进，这可能对酸性肿瘤微环境响应型药物的输送有用。从体外细胞杀伤试验结果和体内肿瘤治疗研究结果可以看出，PAA-Ni _0.85 Se-DOX NP在杀死4T1乳腺癌细胞方面表现出明显的协同作用。因此，本研究提出了一种由超小型PAA-Ni _0.85 Se NPs组成的多功能治疗剂，可用于潜在的癌症治疗，而无需长期毒性。