多功能^(19)F磁共振/CT成像及光热/化学联合治疗纳米平台用于肿瘤诊疗

Multifunctional ^(19)FMR/CT Imaging and Combined Photothermo-/Chemo-therapy Nanoplatform for Tumor Diagnosis and Treatment

开发具有多种成像模式指导的高效诊疗一体化纳米平台对于肿瘤精准诊断治疗和疗效评估具有广阔的应用前景,同时也面临着巨大挑战。光热疗法(PTT)是一种特异性强、副作用小的非侵入性癌症治疗方法,通过将Au与Cu_(7)S_(4)耦合制备而成的Cu_(7)S_(4)/Au异质结可以将吸收调节至808 nm的近红外窗口,使其具有优良的近红外光热效应,这有效避免了生物背景干扰,增大了组织穿透能力和深度,也减少了对正常组织的损伤。同时引入X射线衰减能力强的金赋予了异质结良好的CT成像功能。随后,利用油胺修饰的聚琥珀酰亚胺两亲高分子(PSI_(OAm))通过超声乳化实现对全氟冠醚(PFCE,作为氟源)、紫杉醇(PTX)以及Cu_(7)S_(4)/Au异质结纳米颗粒进行包封组装获得Cu_(7)S_(4)/Au-^(19)F-PTX@PSI纳米复合探针,因而将^(19)F磁共振(^(19)FMR)/CT成像和光热/化学药物联合治疗整合于一个纳米平台。^(19)FMRI、CT及PTT模式相互匹配,均有利并奏效于深部肿瘤成像或治疗。体外和小鼠活体实验结果表明,该纳米探针具有良好的生物相容性和出色的^(19)FMRI/CT及近红外光热成像能力,光热与化疗联合治疗显著抑制了实体肿瘤的生长。研究所展示的多功能诊疗一体化纳米平台为构建新型高效纳米诊疗试剂提供了有益的设计思路和合成策略,有望在将来癌症诊断和治疗中发挥潜力。

The development of multimodal imaging-guided integrated diagnosis and treatment nanoplatforms has broad application prospects for accurate tumor diagnosis,treatment and efficacy evaluations,but also faces great challenges.Photothermal therapy(PTT)is a non-invasive cancer treatment with strong specificity and less side effects.In this study,the Cu_(7)S_(4)/Au heterojunction prepared by coupling Au with Cu_(7)S_(4) can adjust the absorption to a near-infrared window of 808 nm,thus exhibiting excellent near-infrared photothermal effect,which effectively avoids biological background interference,increases tissue penetration ability and depth,and reduces damage to normal tissues.Meanwhile,the introduction of Au with strong X-ray attenuation ability endowed the heterojunction with desired CT imaging function.Subsequently,the oleamine-modified polysuccinimide amphiphilic molecule(PSI_(OAm))was used to encapsulate and assemble perfluorocarboxane(PFCE,as the fluorine source),paclitaxel(PTX)and Cu 7S 4/Au heterojunction nanoparticles into Cu_(7)S_(4)/Au-^(19)F-PTX@PSI nanocomposite probes,thus integrating ^(19)F magnetic resonance(^(19)FMR)/CT imaging and combined photothermo-/chemo-therapy into a nanoplatform.^(19)FMRI,CT and PTT modalities matched each other and were all beneficial and effective in deep-seated tumor imaging of treatment.In vitro and in vivo mouse experimental results showed that the nanoprobe had good biocompatibility and remarkable ^(19)FMRI/CT and near-infrared photothermal imaging capabilities,and the combination of photothermo-/chemo-therapy significantly inhibited the growth of solid tumors.The multifunctional integrated nanoplatform demonstrated in this study will provide novel design and synthetic strategies for the construction of new and efficient diagnostic and therapeutic nanoreagents,which are expected to play a potential role in cancer diagnosis and treatment in the future.