A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite†,Chemical Science

当前位置： X-MOL 学术 › Chem. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite†
Chemical Science ( IF 7.6 ) Pub Date : 2018-03-05 00:00:00 , DOI: 10.1039/c8sc00098k
Zhengze Yu ₁ , Yegang Ge ₁ , Qiaoqiao Sun ₁ , Wei Pan ₁ , Xiuyan Wan ₁ , Na Li ₁ , Bo Tang ₁

Affiliation

Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen (¹O₂) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.

中文翻译：

利用可切换 DNA/上转换纳米复合材料实现精确肿瘤靶向和高效光动力治疗的预保护策略†

基于叶酸（FA）的肿瘤特异性靶向是癌症治疗中最常见和最重要的方法之一。然而，叶酸受体（FR）在正常组织中的表达会导致意想不到的靶向性和不理想的治疗效果。为了解决这个问题，我们开发了一种预保护策略，使用可切换的 DNA/上转换纳米复合材料来实现精确的肿瘤靶向和高效的光动力治疗 (PDT)，该复合材料可以在酸性肿瘤微环境中触发。DNA/上转换纳米复合材料由聚丙烯酸（PAA）涂覆的上转换纳米粒子（UCNP）组成，其表面使用不同长度的FA和二氢卟酚e6（Ce6）功能化的DNA序列进行修饰。最初，较短 DNA 上的 FA 受到较长 DNA 的保护，以防止与正常细胞上的 FR 结合。一旦到达酸性肿瘤微环境，富含C碱基的较长DNA形成C四联体，导致FA基团暴露，FA和FR结合在癌细胞膜上，实现精准靶向。同时，光敏剂二氢卟酚e6（Ce6）接近UCNPs表面，通过福斯特共振能量转移（FRET）在近红外光下激发Ce6产生单线态氧（¹ O _{2 ）。}体内实验表明，通过预保护策略实现了更高的肿瘤靶向效率，并极大地抑制了肿瘤的生长。

更新日期：2018-03-05

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11