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Microenvironment-activated nanoparticles for oxygen self-supplemented photodynamic cancer therapy

机译：微环境 - 激活的纳米粒子用于氧自补充光动力癌疗法

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摘要

Tumor hypoxia, as a hallmark of most solid tumors, poses a serious impediment to O-2-dependent anticancer therapies, such as photodynamic therapy (PDT). Although utilizing nanocarriers to load and transport O-2 to tumor tissues has been proved effective, the therapeutic outcomes have been impeded by the low O-2 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-2 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-2@(NPCe6+PFOB)-N-DA could even alleviate the pre-existing tumor hypoxia. After intravenous injection, O-2@(NPCe6+PFOB)-N-DA exhibited significant tumor accumulation and retention, and potent tumor growth inhibition compared to traditional PDT. Overall, the O-2@(NPCe6+PFOB)-N-DA mediated O-2 self-supplemented PDT with tumor acidic microenviornment-activated cell penetration provides a promising strategy in anticancer treatment.
机译：肿瘤缺氧作为大多数实体肿瘤的标志，对O-2依赖性抗癌治疗的严重障碍，例如光动力治疗（PDT）。虽然利用纳米载体来荷载和运输肿瘤组织，但已经证明有效，但纳米载体的低O-2容量和有限的肿瘤渗透已经阻碍了治疗结果。为了解决这些问题，我们将全氟辛基部分纳入纳米载体，通过含氟核相互作用改善全氟辛基溴的包封，导致纳米载体的升高的O-2容量。同时，为了增强肿瘤细胞穿透能力以及减少网状内皮系统识别，纳米载体进一步用细胞穿透肽装饰，其通过酸不稳定的酰胺键掩盖，延长循环时间和酸 - 活性细胞渗透。体外研究证明，除了在低剂量下显着提高氯化氯6（CE6）的光氧化，甚至可以缓解所列肿瘤缺氧的合理设计的O-2 @（NPCE6 + PFOB）-N-DA。静脉注射后，与传统PDT相比，O-2 @（NPCE6 + PFOB）-N-DA表现出显着的肿瘤积累和保留，并且有效的肿瘤生长抑制。总的来说，O-2 @（NPCE6 + PFOB）-N-DA介导的O-2具有肿瘤酸性微生物激活细胞渗透的自我补充的PDT为抗癌治疗提供了有希望的策略。

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  • 来源
    《Biomaterials Science》 |2020年第1期|共9页
  • 作者

    Liu Hang; Jiang Wei; Wang Qin; Xia Jinxing; Yu Wenhao; Wang Yucai; Wang Yanmei;

  • 作者单位

    Univ Sci &

    Technol China Dept Polymer Sci &

    Engn CAS Key Lab Soft Matter Chem Hefei 230026 Peoples R China;

    Univ Sci &

    Technol China Hefei Natl Lab Phys Sci Microscale CAS Key Lab Innate Immun &

    Chron Dis Div Mol Med Sch Life Sci Hefei 230027 Peoples R China;

    Univ Sci &

    Technol China Hefei Natl Lab Phys Sci Microscale CAS Key Lab Innate Immun &

    Chron Dis Div Mol Med Sch Life Sci Hefei 230027 Peoples R China;

    Anhui Med Univ Affiliated Hosp 1 Hefei 230022 Peoples R China;

    Univ Sci &

    Technol China Dept Polymer Sci &

    Engn CAS Key Lab Soft Matter Chem Hefei 230026 Peoples R China;

    Univ Sci &

    Technol China Hefei Natl Lab Phys Sci Microscale CAS Key Lab Innate Immun &

    Chron Dis Div Mol Med Sch Life Sci Hefei 230027 Peoples R China;

    Univ Sci &

    Technol China Dept Polymer Sci &

    Engn CAS Key Lab Soft Matter Chem Hefei 230026 Peoples R China;

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  • 正文语种 eng
  • 中图分类 分子生物学;
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