Abstract：
Tumor starvation therapy utilizing glucose oxidase (GOx), has gained traction due to its non-invasive and bio-safe attributes. However, its effectiveness is often hampered by severe hypoxia in the tumor microenvironment (TME), limiting GOx\'s catalytic activity. To address this issue, a multifunctional nanosystem based on mesoporous polydopamine nanoparticles (MPDA NPs) was developled to alleviate TME hypoxia. This nanosystem integrated GOx modification and oxygenated perfluoropentane (PFP) encapsulation to address hypoxia-related challenges in the TME. Under NIR laser irradiation, the MPDA NPs exhibit significant photothermal conversion efficacy, activating targeted tumor photothermal therapy (PTT), while also serving as proficient photoacoustic (PA) imaging agents. The ensuing temperature rise facilitates oxygen (O2) release and induces liquid-gas conversion of PFP, generating microbubbles for enhanced ultrasound (US) imaging signals. The supplied oxygen alleviates local hypoxia, thereby enhancing GOx-mediated endogenous glucose consumption for tumor starvation. Overall, the integration of ultrasound/photoacoustic dual imaging-guided PTT and starvation therapy within MPDA-GOx@PFP@O2 nanoparticles (MGPO NPs) presents a promising platform for enhancing the efficacay of tumor treatment by overcoming the complexities of the TME. STATEMENT OF SIGNIFICANCE: A multifunctional MPDA-based theranostic nanoagent was developed for US/PAI imaging-guided PTT and starvation therapy against tumor hypoxia by direct O2 delivery. The incorporation of oxygenated perfluoropentane (PFP) within the mesoporous structure of MGPO not only enables efficient US imaging but also helps in alleviating tumor hypoxia. Moreover, the strong near-infrared (NIR) absorption of MGPO NPs promote the generation of PFP microbubbles and release of oxygen, thereby enhancing US imaging and GOx-mediated starvation therapy. Such a multifunctional nanosystem leverages synergistic effects to enhance therapeutic efficacy while incorporating US/PA imaging for precise visualization of the tumor.
摘要：
利用葡萄糖氧化酶（GOx）的肿瘤饥饿治疗，由于其非侵入性和生物安全属性，获得了牵引力。然而,它的有效性往往受到肿瘤微环境（TME）严重缺氧的阻碍，限制GOx的催化活性。为了解决这个问题，开发了一种基于介孔聚多巴胺纳米颗粒（MPDANPs）的多功能纳米系统，以缓解TME缺氧。该纳米系统集成了GOx修饰和含氧全氟戊烷（PFP）和氧气（O2）的负载，以解决TME中与缺氧相关的挑战。在近红外激光照射下，MPDANP表现出显著的光热转换效率，激活靶向肿瘤光热治疗（PTT），同时也用作熟练的光声（PA）成像剂。随后的温度升高促进O2释放并诱导PFP的液-气转化，生成用于增强超声(US)成像信号的微泡。供应的氧气缓解了局部缺氧，从而增强用于肿瘤饥饿的GOx介导的内源性葡萄糖消耗。总的来说,超声/光声双重成像引导下的PTT和饥饿治疗在MPDA-GOx@PFP@O2纳米颗粒(MGPONPs)中的整合为通过克服TME的复杂性提高肿瘤治疗效果提供了一个有前景的平台.重要声明：开发了一种基于MPDA的多功能治疗纳米药物，用于US/PAI成像指导的PTT和通过直接O2递送对抗肿瘤缺氧的饥饿治疗。在MGPO的介孔结构中掺入含氧全氟戊烷（PFP）不仅可以进行有效的US成像，而且还有助于减轻肿瘤缺氧。此外，MGPONP的强近红外(NIR)吸收促进了PFP微泡的生成和氧气的释放,从而增强US成像和GOx介导的饥饿治疗。这种多功能纳米系统利用协同作用来增强治疗功效,同时结合US/PA成像以精确观察肿瘤。
