Abstract

It is important to enhance penetration depth of nanomedicine and realise rapid drug release simultaneously at targeted tumour for improving anti-tumour efficiency of chemotherapeutic drugs. This project employed sodium alginate (Alg) as matrix material, to establish tumour-responsive nanogels with particle size conversion and drug controlled release functions. Specifically, tumour-targeting peptide CRGDK was conjugated with Alg first (CRGDK-Alg). Then, doxorubicin (DOX) was efficiently encapsulated in CRGDK-FeAlg nanogel during the cross-linking process (CRGDK-FeAlg/DOX). This system was closed during circulation. Once reaching tumour, the particle size of nanogels was reduced to ∼25 nm, which facilitated deep penetration of DOX in tumour tissues. After entering tumour cells, the size of nanogels was further reduced to ∼10 nm and DOX was released simultaneously. Meanwhile, FeAlg efficiently catalysed H₂O₂ to produce •OH by Fenton reaction, achieving local chemodynamic therapy without O₂ mediation. Results showed CRGDK-FeAlg/DOX significantly inhibited tumour proliferation in vivo with V/V0 of 1.13 after treatment, significantly lower than that of control group with V/V0 of 4.79.

摘要

提高纳米药物的渗透深度，同时实现靶向肿瘤的快速药物释放，对于提高化疗药物的抗肿瘤效率具有重要意义。本项目以海藻酸钠（Alg）为基质材料，构建具有粒径转换和药物控释功能的肿瘤响应纳米凝胶。具体而言，肿瘤靶向肽 CRGDK 首先与 Alg 偶联（CRGDK-Alg）。然后，在交联过程（CRGDK-FeAlg/DOX）中，阿霉素（DOX）被有效地封装在 CRGDK-FeAlg 纳米凝胶中。该系统在流通过程中是关闭的。一旦到达肿瘤，纳米凝胶的粒径就会减小到 25 nm，这有助于 DOX 在肿瘤组织中的深度渗透。进入肿瘤细胞后，纳米凝胶的尺寸进一步减小到约 10 nm，同时释放 DOX。同时，FeAlg 有效地催化了 H₂ O ₂通过芬顿反应生成•OH，实现无O ₂介导的局部化学动力学治疗。结果表明CRGDK-FeAlg / DOX显著抑制肿瘤增殖的体内与V / V的1.13 0处理后，比与对照组的显著降低V / V的4.79 0。