Liver Disease Center , The First Affiliated Hospital of Fujian Medical University , Fuzhou 350005 , P. R. China.
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province , Mengchao Hepatobiliary Hospital of Fujian Medical University , Fuzhou 350025 , P. R. China.
ACS Appl Mater Interfaces. 2019 Mar 13;11(10):9804-9813. doi: 10.1021/acsami.8b21820. Epub 2019 Feb 27.
Recently reported black phosphorus quantum dots (BPQDs) possess unique photocatalysis activities. However, the environmental instability accompanied by a hypoxic tumor microenvironment (TME) seriously hindered the bioapplications of BPQDs, especially in oxygen-dependent photodynamic therapy (PDT). Here, we construct a hepatocellular carcinoma (HCC)-specific targeting aptamer "TLS11a"-decorated BPQDs-hybridized nanocatalyst, which can specifically target HCC tumor cells and self-compensate oxygen (O) into hypoxic TME for enhancing PDT efficiency. The BPQD-hybridized mesoporous silica framework (BMSF) with in situ synthesized Pt nanoparticles (PtNPs) in the BMSF is simply prepared. After being decorated by TLS11a aptamer/Mal-PEG-NHS, the resultant nanosystem (refer as Apt-BMSF@Pt) exhibits excellent environmental stability, active targeting ability to HCC cells, and self-compensation ability of oxygen. Compared with the PEG-BMSF@Pt without HO incubation, the PEG-BMSF@Pt nanocatalyst exhibits 4.2-folds O and 1.6-folds O generation ability in a mimetic closed-system in the presence of both HO and near-infrared laser. In a mouse model, the Apt-BMSF@Pt can effectively accumulate into tumor sites, and the core of BMSF subsequently can act as a photosensitizer to generate reactive oxygen species, while the PtNPs can serve as a catalyst to convert HO into O for enhancing PDT through self-compensation mechanisms in hypoxic TME. By comparison of the tumor volume/weight, H&E, and immunohistochemical analysis, the excellent antitumor effects with minimized side effects of our Apt-BMSF@Pt could be demonstrated in vivo. Taken together, the current study suggests that our Apt-BMSF@Pt could act as an active targeting nanocatalyst for programmable killing of cancer cells in hypoxic TME.
最近报道的黑磷量子点（BPQDs）具有独特的光催化活性。然而，伴随缺氧肿瘤微环境（TME）的不稳定性严重阻碍了 BPQDs 的生物应用，特别是在依赖氧的光动力疗法（PDT）中。在这里，我们构建了一种肝细胞癌（HCC）特异性靶向适体“TLS11a”修饰的 BPQDs-杂交纳米催化剂，它可以特异性靶向 HCC 肿瘤细胞，并自我补偿缺氧 TME 中的氧气（O），以提高 PDT 效率。通过在介孔硅骨架（BMSF）中原位合成 Pt 纳米颗粒（PtNPs），简单制备了 BPQD 杂交的介孔硅骨架（BMSF）。经 TLS11a 适体/Mal-PEG-NHS 修饰后，所得纳米系统（命名为 Apt-BMSF@Pt）表现出优异的环境稳定性、对 HCC 细胞的主动靶向能力和对氧气的自我补偿能力。与未经 HO 孵育的 PEG-BMSF@Pt 相比，在含有 HO 和近红外激光的模拟封闭系统中，PEG-BMSF@Pt 纳米催化剂的 O 生成能力提高了 4.2 倍，O 生成能力提高了 1.6 倍。在小鼠模型中，Apt-BMSF@Pt 可以有效地聚集到肿瘤部位，BMSF 的核心随后可以作为光敏剂产生活性氧，而 PtNPs 可以作为催化剂通过缺氧 TME 中的自我补偿机制将 HO 转化为 O 以增强 PDT。通过肿瘤体积/重量、H&E 和免疫组织化学分析，体内实验证明了我们的 Apt-BMSF@Pt 具有优异的抗肿瘤效果和最小的副作用。综上所述，本研究表明，我们的 Apt-BMSF@Pt 可以作为一种主动靶向纳米催化剂，用于在缺氧 TME 中可编程杀伤癌细胞。
