Laboratory of Molecular Imaging and Nanomedicine (LOMIN) , National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH) , Bethesda , Maryland 20892 , United States.
Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM) , Nanjing University of Posts & Telecommunications , Nanjing 210023 , China.
ACS Nano. 2018 Mar 27;12(3):2610-2622. doi: 10.1021/acsnano.7b08628. Epub 2018 Feb 21.
Combination of photoacoustic (PA) and ultrasound (US) imaging offers high spatial resolution images with deep tissue penetration, which shows great potential in applications in medical imaging. Development of PA/US dual-contrast agents with high contrast and excellent biocompatibility is of great interest. Herein, an organic semiconducting photoacoustic nanodroplet, PS-PDI-PAnD, is developed by stabilizing low-boiling-point perfluorocarbon (PFC) droplet with a photoabsorber and photoacoustic agent of perylene diimide (PDI) molecules and coencapsulating the droplet with photosensitizers of ZnFPc molecules. Upon irradiation, the PDI acts as an efficient photoabsorber to trigger the liquid-to-gas phase transition of the PFC, resulting in dual-modal PA/US imaging contrast as well as photothermal heating. On the other hand, PFC can serve as an O reservoir to overcome the hypoxia-associated resistance in cancer therapies, especially in photodynamic therapy. The encapsulated photosensitizers will benefit from the sustained oxygen release from the PFC, leading to promoted photodynamic efficacy regardless of pre-existing hypoxia in the tumors. When intravenously injected into tumor-bearing mice, the PS-PDI-PAnDs show a high tumor accumulation via EPR effect. With a single 671 nm laser irradiation, the PS-PDI-PAnDs exhibit a dual-modal PA/US imaging-guided synergistic photothermal and oxygen self-enriched photodynamic treatment, resulting in complete tumor eradication and minimal side effects. The PS-PDI-PAnDs represents a type of PFC nanodroplets for synergistic PDT/PTT treatment upon a single laser irradiation, which is expected to hold great potential in the clinical translation in dual-modal PA/US imaging-guided combinational cancer therapy.
光声（PA）和超声（US）成像的组合提供了具有深层组织穿透能力的高空间分辨率图像，在医学成像应用中显示出巨大的潜力。开发具有高对比度和优异生物相容性的 PA/US 双对比剂非常有趣。本文通过用苝二酰亚胺（PDI）分子的光吸收剂和光声剂稳定低沸点全氟碳（PFC）液滴，并将液滴与 ZnFPc 分子的光敏剂共包封，开发了一种有机半导体光声纳米液滴 PS-PDI-PAnD。光照后，PDI 作为一种高效的光吸收剂触发 PFC 的液-气相转变，从而产生双模态 PA/US 成像对比以及光热加热。另一方面，PFC 可以作为 O 储库，克服癌症治疗中与缺氧相关的耐药性，特别是在光动力治疗中。包封的光敏剂将受益于 PFC 持续释放的氧气，从而促进光动力疗效，而与肿瘤中预先存在的缺氧无关。当静脉注射到荷瘤小鼠体内时，PS-PDI-PAnDs 通过 EPR 效应表现出高肿瘤积累。单次 671nm 激光照射下，PS-PDI-PAnDs 表现出双模态 PA/US 成像引导的协同光热和氧气自富光动力治疗，导致完全肿瘤消除和最小的副作用。PS-PDI-PAnDs 代表了一种用于协同 PDT/PTT 治疗的 PFC 纳米液滴，有望在双模态 PA/US 成像引导的联合癌症治疗的临床转化中具有巨大潜力。
