Chlorin e6 Functionalized Theranostic Multistage Nanovectors Transported by Stem Cells for Effective Photodynamic Therapy.

Chlorin e6 Functionalized Theranostic Multistage Nanovectors Transported by Stem Cells for Effective Photodynamic Therapy.
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氯素E6通过干细胞运输的有效光动力疗法运输的功能化疗法多阶段纳米腔。

DOI:
10.1021/acsami.7b05766
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发表时间:
2017-07-19
影响因子:
9.5
通讯作者:
Tasciotti E
Tasciotti E
中科院分区:
材料科学2区
文献类型:
--
作者:
Näkki S;Martinez JO;Evangelopoulos M;Xu W;Lehto VP;Tasciotti E

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癌症治疗迫切需要实现特定部位和靶向递送的方法,以提供有效的解决方案来减少不良的、非靶向的副作用。在这里,我们使用类似特洛伊木马的策略来携带光敏剂氯化e6连接的多孔硅多阶段纳米载体和肿瘤归巢间充质干细胞,用于靶向光动力治疗和诊断。多阶段纳米载体固有的多功能性使光敏剂的结合能够在光动力疗法中实现精确的细胞死亡诱导(60%),同时保持负载各种有效载荷的能力,如抗肿瘤药物和诊断纳米颗粒。此外,内化多阶段纳米载体的间充质干细胞保留了它们的增殖模式和体外迁移和渗透乳腺癌细胞的亲和力。携带光敏剂结合的多阶段纳米载体的间充质干细胞体内给药证实了它们对肿瘤部位的趋向性,表现出与对照细胞相似的靶向动力学。此外,在活体光动力治疗后,这种方法导致局部肿瘤细胞活力下降了70%。综上所述,这些结果表明,通过干细胞运输的光敏剂结合的多阶段纳米载体如何针对肿瘤并用于有效的部位特异性癌症治疗,同时潜在地将潜在的负面副作用降至最低,这一概念得到了验证。
Approaches to achieve site-specific and targeted delivery that provide an effective solution to reduce adverse, off target side effects are urgently needed for cancer therapy. Here, we utilized a Trojan-horse-like strategy to carry photosensitizer Chlorin e6 conjugated porous silicon multistage nanovectors with tumor homing mesenchymal stem cells for targeted photodynamic therapy and diagnosis. The inherent versatility of multistage nanovectors permitted the conjugation of photosensitizers to enable precise cell death induction (60%) upon photodynamic therapy, while simultaneously retaining the loading capacity to load various payloads, such as antitumor drugs and diagnostic nanoparticles. Furthermore, the mesenchymal stem cells that internalized the multistage nanovectors conserved their proliferation patterns and in vitro affinity to migrate and infiltrate breast cancer cells. In vivo administration of the mesenchymal stem cells carrying photosensitizer-conjugated multistage nanovectors in mice bearing a primary breast tumor confirmed their tropism toward cancer sites exhibiting similar targeting kinetics to control cells. In addition, this approach yielded in a > 70% decrease in local tumor cell viability after in vivo photodynamic therapy. In summary, these results show the proof-of-concept of how photosensitizer conjugated multistage nanovectors transported by stem cells can target tumors and be used for effective site-specific cancer therapy while potentially minimizing potential negative side effects.
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