CAS Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, P. R. China.
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei 230027, P. R. China.
Biomater Sci. 2020 Jan 1;8(1):370-378. doi: 10.1039/c9bm01537j. Epub 2019 Nov 15.
Tumor hypoxia, as a hallmark of most solid tumors, poses a serious impediment to O-dependent anticancer therapies, such as photodynamic therapy (PDT). Although utilizing nanocarriers to load and transport O to tumor tissues has been proved effective, the therapeutic outcomes have been impeded by the low O capacity and limited tumor penetration of the nanocarriers. To address these problems, we incorporated perfluorooctyl moieties into nanocarriers to improve the encapsulation of perfluorooctyl bromide via fluorophilic interactions, leading to elevated O capacity of the nanocarriers. Meanwhile, to enhance the tumor cell penetrating ability as well as reduce reticuloendothelial system recognition, the nanocarrier was further decorated with a cell-penetrating peptide, which was masked with a protecting group via an acid-labile amide bond for prolonged circulation time and acid-activated cell penetration. The in vitro study demonstrated that, apart from remarkably boosting the photocytoxicity of chlorin 6 (Ce6) at a low dosage, the rationally designed O@NP could even alleviate the pre-existing tumor hypoxia. After intravenous injection, O@NP exhibited significant tumor accumulation and retention, and potent tumor growth inhibition compared to traditional PDT. Overall, the O@NP mediated O self-supplemented PDT with tumor acidic microenviornment-activated cell penetration provides a promising strategy in anticancer treatment.
肿瘤缺氧是大多数实体瘤的一个标志，严重阻碍了 O 依赖性的抗癌疗法，如光动力疗法（PDT）。尽管利用纳米载体将 O 载入并输送到肿瘤组织已被证明是有效的，但由于纳米载体的 O 容量低和有限的肿瘤穿透性，治疗效果受到了阻碍。为了解决这些问题，我们将全氟辛基部分引入纳米载体中，通过亲氟相互作用来提高全氟辛基溴的包封率，从而提高纳米载体的 O 容量。同时，为了增强肿瘤细胞穿透能力并减少网状内皮系统的识别，纳米载体进一步用穿透肽进行了修饰，穿透肽通过酸不稳定的酰胺键与保护基团结合，以延长循环时间和酸激活的细胞穿透。体外研究表明，除了在低剂量下显著提高氯己定（Ce6）的光细胞毒性外，合理设计的 O@NP 甚至可以减轻预先存在的肿瘤缺氧。静脉注射后，与传统 PDT 相比，O@NP 表现出显著的肿瘤积累和保留，以及强大的肿瘤生长抑制作用。总的来说，O@NP 介导的 O 自补充 PDT 具有肿瘤酸性微环境激活细胞穿透的特点，为癌症治疗提供了一种有前途的策略。
