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首页> 美国卫生研究院文献>Theranostics >Self-Luminescing Theranostic Nanoreactors with Intraparticle Relayed Energy Transfer for Tumor Microenvironment Activated Imaging and Photodynamic Therapy
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Self-Luminescing Theranostic Nanoreactors with Intraparticle Relayed Energy Transfer for Tumor Microenvironment Activated Imaging and Photodynamic Therapy

机译：具有粒子内中继能量转移的自发光治疗用纳米反应器用于肿瘤微环境激活的成像和光动力疗法

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The low tissue penetration depth of external excitation light severely hinders the sensitivity of fluorescence imaging (FL) and the efficacy of photodynamic therapy (PDT) in vivo; thus, rational theranostic platforms that overcome the light penetration depth limit are urgently needed. To overcome this crucial problem, we designed a self-luminescing nanosystem (denoted POCL) with near-infrared (NIR) light emission and singlet oxygen (1O2) generation abilities utilizing an intraparticle relayed resonance energy transfer strategy.>Methods: Bis[3,4,6-trichloro-2-(pentyloxycarbonyl) phenyl] oxalate (CPPO) as a chemical energy source with high reactivity toward H2O2, poly[(9,9'-dioctyl-2,7-divinylene-fluorenylene)-alt-2-methoxy- 5-(2-ethyl-hexyloxy)-1,4-phenylene] (PFPV) as a highly efficient chemiluminescence converter, and tetraphenylporphyrin (TPP) as a photosensitizer with NIR emission and 1O2 generation abilities were coencapsulated by self-assembly with poly(ethyleneglycol)-co-poly(caprolactone) (PEG-PCL) and folate-PEG-cholesterol to form the POCL nanoreactor, with folate as the targeting group. A series of in vitro and in vivo analyses, including physical and chemical characterizations, tumor targeting ability, tumor microenvironment activated imaging and photodynamic therapy, as well as biosafety, were systematically investigated to characterize the POCL.>Results: The POCL displayed excellent NIR luminescence and 1O2 generation abilities in response to H2O2. Therefore, it could serve as a specific H2O2 probe to identify tumors through chemiluminescence imaging and as a chemiluminescence-driven PDT agent for inducing tumor cell apoptosis to inhibit tumor growth due to the abnormal overproduction of H2O2 in the tumor microenvironment. Moreover, the folate ligand on the POCL surface can further improve the accumulation at the tumor site via a receptor-mediated mechanism, thus enhancing tumor imaging and the therapeutic effects both in vitro and in vivo but without any observable systemic toxicity.>Conclusion: The nanosystem reported here might serve as a targeted, smart, precise, and noninvasive strategy triggered by the tumor microenvironment rather than by an outside light source for cancer NIR imaging and PDT treatment without limitations on penetration depth.
机译：外部激发光的低组织穿透深度严重阻碍了体内荧光成像（FL）的敏感性和光动力疗法（PDT）的功效；因此，迫切需要克服光穿透深度极限的合理的治疗台。为了克服这个关键问题，我们设计了一种自发光纳米系统（表示为POCL），该系统具有近红外（NIR）发光和单线态氧（ 1 O2）产生能力，采用粒子内中继共振能量转移策略。>方法：草酸双[3,4,6-三氯-2-（戊氧基羰基）苯基]草酸酯（CPPO）作为对H2O2具有高反应活性的化学能源，聚[（9,9'-二辛基-2,7-二亚乙烯基-亚芴基）-alt-2-甲氧基-5-（2-乙基-己氧基）-1,4-亚苯基]（PFPV）作为高效的化学发光转换器，四苯基卟啉（TPP）作为高效的化学发光转换器通过自组装与聚乙二醇-共聚己内酯（PEG-PCL）和叶酸-PEG-胆固醇自组装共封装具有近红外发射和 1 O2生成能力的光敏剂，形成POCL纳米反应器，以叶酸作为定位组。系统研究了一系列的体外和体内分析，包括理化性质，肿瘤靶向能力，肿瘤微环境激活的成像和光动力疗法以及生物安全性。>结果： POCL表现出出色的近红外发光和响应H2O2的 1 O2生成能力。因此，它可以作为一种特异性的H2O2探针，通过化学发光成像来鉴定肿瘤，并且可以用作化学发光驱动的PDT试剂，以诱导肿瘤细胞凋亡，从而抑制由于肿瘤微环境中H2O2异常过量产生而导致的肿瘤生长。此外，POCL表面的叶酸配体可以通过受体介导的机制进一步改善肿瘤部位的蓄积，从而增强了体内外的肿瘤成像和治疗效果，但没有任何可观察到的全身毒性。>结论：此处报道的纳米系统可以作为一种目标，智能，精确且无创的策略，由肿瘤微环境触发，而不是由外部光源触发，用于癌症NIR成像和PDT治疗，而对穿透深度没有限制。

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