Abstract：
Stimulating the release of small nanoparticles (NPs) from a larger NP via the application of an exogenous stimulus offers the potential to address the different size requirements for circulation versus penetration that hinder chemotherapeutic drug delivery. Herein, we report a size-switching nanoassembly-based drug delivery system comprised of ultrasmall starch nanoparticles (SNPs, ∼20-50 nm major size fraction) encapsulated in a poly(oligo(ethylene glycol) methyl ether methacrylate) nanogel (POEGMA, ∼150 nm major size fraction) cross-linked via supramolecular PEG/α-cyclodextrin (α-CD) interactions. Upon heating the nanogel using a non-invasive, high-intensity focused ultrasound (HIFU) trigger, the thermoresponsive POEGMA-CD nanoassemblies are locally de-cross-linked, inducing in situ release of the highly penetrative drug-loaded SNPs. HIFU triggering increased the release of nanoassembly-loaded DOX from 17 to 37% after 3 h, a result correlated with significantly more effective tumor killing relative to nanoassemblies in the absence of HIFU or drug alone. Furthermore, 1.5× more total fluorescence was observed inside a tumor spheroid when nanoassemblies prepared with fluorophore-labeled SNPs were triggered with HIFU relative to the absence of HIFU. We anticipate this strategy holds promise for delivering tunable doses of chemotherapeutic drugs both at and within a tumor site using a non-invasive triggering approach.
摘要：
通过施加外源刺激刺激从较大NP释放小纳米颗粒(NP)提供了解决阻碍化疗药物递送的循环与渗透的不同尺寸要求的潜力。在这里，我们报告了一种基于尺寸转换纳米组装的药物递送系统，该系统由超小淀粉纳米颗粒(SNP，~20-50纳米主要尺寸部分)封装在聚(低聚(乙二醇)甲基醚甲基丙烯酸酯)纳米凝胶(POEGMA，~150nm主要尺寸分数)通过超分子PEG/α-环糊精(α-CD)相互作用交联。在使用非侵入性加热纳米凝胶时，高强度聚焦超声（HIFU）触发器，热响应POEGMA-CD纳米组装体是局部去交联的，诱导高渗透性载药SNP的原位释放。3小时后，HIFU触发将纳米组装体加载的DOX的释放从17％增加到37％，与不存在HIFU或单独药物的纳米组装体相比,结果与显著更有效的肿瘤杀伤相关。此外，当相对于不存在HIFU,用HIFU触发用荧光团标记的SNP制备的纳米组件时,在肿瘤球状体内观察到1.5倍以上的总荧光。我们预计该策略有望使用非侵入性触发方法在肿瘤部位和肿瘤部位内提供可调剂量的化疗药物。
