Nanosonosensitizers for Highly Efficient Sonodynamic Cancer Theranostics
Nanosonosensitizers for Highly Efficient Sonodynamic Cancer Theranostics
复制标题
用于高效声动力癌症治疗的纳米声敏剂
DOI：
10.7150/thno.29569
复制
发表时间：
2018-01-01
期刊：
影响因子：
12.4
通讯作者：
Li, Pan
中科院分区：
文献类型：
--
作者：
Huang, Ju;Liu, Fengqiu;Li, Pan
背景：具有诊断成像和靶向治疗功能的多功能纳米平台在精密纳米医学领域引起了极大的兴趣。新兴的声动力疗法(SDT)与光声成像(PA)引导下的声敏剂相结合，有望准确清除癌细胞/组织。方法：将核/壳结构的FA-HMME-MNPs-PLGA纳米粒子(FHMP NPs，FA：叶酸，HMME：血卟啉单甲醚，MNPs：黑色素纳米粒，PLGA：聚(乳酸-羟基乙酸)酸)整合到核/壳结构的FA-HMME-MNPs-PLGA纳米粒子中，用于增强PA显像引导的SDT，并用肿瘤靶向配体FA进一步功能化。PA成像引导的SDT在体外和体内都得到了系统和成功的验证。并对FHMP纳米粒的高生物安全性进行了系统评价。结果：合成的FHMP纳米粒子具有广泛的光吸收，不仅具有较高的PA成像对比度增强能力，而且具有显着的SDT效率。重要的是，这种基于PLGA的纳米平台改善了HMME的光稳定性，增强了声动力学性能，并促进了MNPs向肿瘤区域的输送。同时，还发现并验证了HMME与MNPs之间的联合作用。此外，超声辐射辅助的超声增敏剂可产生ROS介导的对肿瘤细胞/组织的细胞毒作用。对荷瘤小鼠的体外细胞水平和体内系统移植实验表明，FHMP纳米粒辅助ROS对肿瘤细胞的选择性杀伤作用，对肿瘤生长具有积极的抑制作用，且具有较高的生物安全性。结论：成功构建了透气纳米平台，实现了PA影像引导下的乳腺癌细胞/组织立体定向放射治疗。更重要的是，证明了MNPs和HMME在一个平台上具有增强PA成像的综合效果。这种独特的具有多种功能的治疗纳米平台，通过合理利用，为个性化医疗铺平了一条新的道路。
Background: Multifunctional nanoplatforms with diagnostic-imaging and targeted therapeutic functionality (theranostics) are of great interest in the field of precision nanomedicine. The emerging sonodynamic therapy (SDT) combined with sonosensitizers under the guidance of photoacoustic (PA) imaging is highly expected to accurately eliminate cancer cells/tissue. Methods: Unique core/shell-structured theranostic FA-HMME-MNPs-PLGA nanoparticles (FHMP NPs, FA: folate, HMME: hematoporphyrin monomethyl ether, MNPs: melanin nanoparticles, PLGA: poly (lactic-co-glycolic) acid) were constructed by the integration of MNPs (for PA imaging) in the core and HMME in the shell for enhanced PA imaging-guided SDT, which were further functionalized with a tumor-targeting ligand, FA. The PA imaging-guided SDT was systematically and successfully demonstrated both in vitro and in vivo. The high biosafety of FHMP NPs was also systematically evaluated. Results: The synthesized FHMP NPs with a broad optical absorption not only possess high PA-imaging contrast enhancement capability but also exhibit significant SDT efficiency. Importantly, such a PLGA based nanoplatform improved light stability of HMME, enhancing sonodynamic performance and facilitated delivery of MNPs to the tumor region. Meanwhile, a combined effect between HMME and MNPs was discovered and verified. Furthermore, a sonosensitizer assisted by ultrasound irradiation engenders reactive oxygen species (ROS)-mediated cytotoxicity toward tumor cells/tissue. Both in vitro cell-level and systematic in vivo xenograft evaluations on tumor-bearing mice demonstrated that the selective killing effect of ROS on tumor cells was assisted by FHMP NPs, which played an active role in the suppression of tumor growth with high biosafety. Conclusion: A theranostic nanoplatform was successfully constructed, achieving PA imaging-guided SDT against breast cancer cells/tissue. More importantly, MNPs and HMME in one platform with combined effect for enhancing PA imaging was demonstrated. This unique theranostic nanoplatform with multiple capabilities paves a new way toward personalized medicine by rational utilization.