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制剂工作者利用肿瘤微环境h?/span>pH?/span>?/span>H2O2和高表达的特异性受体等特征Q构?/span>pH/H2O2敏感和针?/span>?/span>表达肿瘤特异性受体的多功能纳c物递送^収ͼ旨在药物有效靶向递送到肿瘤l织或细?yu)，实现肿瘤的靶向治疗。手性介孔硅U米是介孔无机材?/span>Q?/span>除具有无机硅材料的刚性骨架、较大的比较面积和孔体积、可调节的介孔孔道和表面丰富的硅醇基{优点外Q还拥有手性特异性和状形貌的拓扑学优势Q经必要的化学修饰后Q可以实现肿瘤的靶向递送ƈ用于肿瘤的治疗?/span>


q日Q?/span>沈阳药科大学药学院李三鸣教授Nl和中国ȝ大学李鹤然课题组在?/span>ACS Applied Materials & Interfaces》期刊上发表了题?/span>?/span>pH/H2O2 Dual-Responsive Chiral Mesoporous Silica Nanorods Coated with a Biocompatible Active Targeting Ligand for Cancer Therapy?span style="font-family:宋体;">的研I性论文。文中构建的递药pȝ是在表面易于功能化的状介孔纳c粒的基上，苯酸频哪醇酯嫁接到棒状介孔硅U米_表面，赋予介孔纳cx的手性和?/span>H2O2的敏感性，再将抗癌药阿霉素载入U米_子的孔道中Q然后在_子表面包裹了透明质酸-环糊_օ聚物作ؓ?/span>分子开?/span>?/span>Q即可防止阿霉素q早释放又能可赋予粒子主动靶向性。该pȝ是一U安全、有效的pH/H2O2 双重敏感状手性介孔硅U米递送^収ͼhd靶向?/span>pH/H2O2双重敏感的多重抗癌优ѝ研I结果证明，载体中的阉K素在?/span>pH肿瘤微环境下原位释药Q同时能够提高肿瘤微环境?/span>H2O2度Q提高粒子在肿瘤部位H2O2的敏感特性，发挥高效抗癌的作用。该研究从系l构建、评价到l胞(yu)和整体动物层面的pd药理药效研究l果Q证明这是利用肿瘤微环境特异性构建的多功能无机硅U米药物递送^台的一个成功案例，瘤靶向递药pȝ的设计与构徏提供了一个新思\?/span>



C意?/span>1. Q?/span>AQ?/span>pH/H2O2 双重敏感?/span>HA-CD/DOX-PCMSRs的合成\径；Q?/span>BQ通过CD44受体介导肿瘤l胞(yu)内化HA-CD/DOX-PCMSRs?/span>该粒?/span>?/span>pH/H2O2双重刺激因子作用下释放药物的机制?/span>


本文要点



?/span>1. HA-CD/DOX-PCMSRs的表征。（AQ?/span>BQ?/span>IR谱图Q（C-EQ?/span>XPS光电(sh)子能谱；Q?/span>FQ?/span>BET{温U；Q?/span>GQ孔径分布；Q?/span>HQ?/span>SAXS谱图Q（IQ?/span>TGA曲线?/span>


?/span>2. 载体典型?/span>TEM照片Q?/span>A-CQ和_径分布Q?/span>DQ?/span>


?/span>3. Q?/span>AQ在H2O2度分别?/span>0?/span>1.0?/span>2.0?/span>10 mM?/span>pH 7.4酸盐缓冲液?/span>DOX-PCMSRs的体外释放曲U；Q?/span>BQ在H2O2度分别?/span>0?/span>1.0?/span>2.0?/span>10 mM?/span>pH 7.4酸盐缓冲液或含?/span>10 mM H2O2 ?/span>pH 5.0酸盐缓冲液?/span>HA-CD/DOX-PCMSRs的体外释放曲U；Q?/span>CQ在pH 5.0Q?/span>pH 6.5 ?/span>pH 7.4的磷酸盐~冲液中HA-CD/DOX-PCMSRs的体外释放曲U；Q?/span>DQ与DOX?/span>PCMSRs?/span>DOX-PCMSRs?/span>HA-CD/DOX-PCMSR共孵育的3T3l胞(yu)?/span>4T1l胞(yu)?/span>H2O2的相?/span>表达?/span>


?/span>4. HA?/span>Cy5.5-HA-CD/DOX-PCMSRs的竞争性抑制研I?/span>4T1l胞(yu)Q先?/span>HA共孵?/span>2 hQ?/span>AQ和NIH/3T3l胞(yu) Q?/span>BQ与Cy5.5标记?HA-CD/DOX-PCMSRs 共孵?/span>2 h?/span>4 h后的CLSM?/span>片?/span>4T1l胞(yu)Q?/span>?/span>?/span>HA共孵?/span>2 hQ?/span>CQ和NIH/3T3l胞(yu)Q?/span>DQ与Cy5.5-标记?/span>HA-CD/DOX-PCMSRs 共孵?/span>2 h?/span>4 h后的式l果?/span>


?/span>5. Q?/span>AQ?/span>BQ?/span>NIH/3T3?/span>4T1l胞(yu)?/span>DOXQ?/span>DOX-PCMSRs?/span>HA-CD/DOX-PCMSRs 共孵?/span> 24?48?72 h后的体外l胞(yu)毒性；Q?/span>CQ?/span>4T1l胞(yu)?/span>DOX, DOX-PCMSRs?HA-CD/DOX-PCMSRs共孵?/span>24 h后的z?/span>/ȝ?yu)图片；Q?/span>DQ?/span>4T1l胞(yu)?/span>DOX, DOX-PCMSRs?HA-CD/DOX-PCMSRs共孵?/span>24 h后的l胞(yu)凋亡l果?/span>


?/span>6. HA-CD/DiR-PCMSRs的生物分布和肿瘤靶向性。（AQ静脉注?/span>DiR-PCMSRs?/span>HA-CD/DiR-PCMSRs后，4T1肿瘤l胞(yu)L鼠在不同时间点的体内成像照片；Q?/span>BQ静脉注?/span>DiR-PCMSRs?/span>HA-CD/DiR-PCMSRs 24 h后，M器官和肿瘤的zM成像照片Q（CQ静脉注?/span>DiR-PCMSRs?/span>HA-CD/DiR-PCMSRs 24 h后，主要脏器和离体瘤块中DiR-PCMSRs?/span>HA-CD/DiR-PCMSRs的半定量荧光强度?/span>


?/span>7. HA-CD/DOX-PCMSRs?/span>4T1l胞(yu)L鼠的抗癌作用和生物安全性评估。（AQ治疗方案；Q?/span>BQ整个治疗过E的肿瘤生长曲线Q（CQ治疗期间荷瘤小鼠体重的动态变化；Q?/span>DQ在21天治疗过E你Q离体肿瘤和q_肿瘤重量的典型图片；Q?/span>FQ不同治疗组肿瘤l织?/span>H&E?/span>TUNEL染色?/span>


沈阳药科大学药学院博士生研究?/span>王玉?/span>论文W一作者，研究得到国家自然U学基金Q?/span>No. 81773672 ?/span>No. 81903550Q?/span>资助?/span>


相关链接

https://doi.org/10.1021/acsami.1c08532

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