State Key Laboratory of Advanced Technology for Materials Synthesis and Processing, Wuhan University of Technology, Wuhan, 430070, China.
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China.
Nanoscale. 2022 May 26;14(20):7473-7479. doi: 10.1039/d2nr01175a.
Highly efficient delivery of nanoagents to the tumor region remains the primary challenge for cancer nanomedicine. Herein, we propose a NO-mediated tumor microenvironment (TME) remodeling strategy for the high-efficient delivery of nanoagents into tumor. Quantum dots (QDs) with bright fluorescence in the near-infrared IIb (NIR-IIb, 1500-1700 nm) window and high photothermal conversion efficiency were encapsulated into liposomes for the imaging-guided photothermal therapy (PTT) of tumor. The fabrication of PEG and arginine-glycine-aspartate (RGD) peptide on liposomes ensured the prolonged circulation and active targeting to tumor. Moreover, the loading of a natural NO generator L-arginine in liposomes realized the continuous generation of NO in the acidic TME. By co-localization fluorescence imaging and western blot of tumor tissue, we confirmed that the release of NO activated the expression of metalloproteinases in TME and further degraded Collagen I in the peripheral region of the tumor, thus removing the barrier for the permeation of liposomes. Attributed to the enhanced accumulation of liposomes inside the tumor, NIR IIb imaging-guided PTT was achieved with remarkable therapeutic efficacy.
高效地将纳米制剂递送到肿瘤区域仍然是癌症纳米医学的主要挑战。在此，我们提出了一种通过 NO 介导的肿瘤微环境 (TME) 重塑策略，以实现高效递送到肿瘤的纳米制剂。将具有在近红外二区（NIR-IIb，1500-1700nm）窗口中具有明亮荧光和高光热转换效率的量子点（QDs）封装到脂质体中，用于肿瘤的成像引导光热治疗（PTT）。在脂质体上修饰聚乙二醇（PEG）和精氨酸-甘氨酸-天冬氨酸（RGD）肽，以确保延长循环时间和主动靶向肿瘤。此外，在脂质体中负载天然一氧化氮供体 L-精氨酸实现了在酸性 TME 中持续产生 NO。通过肿瘤组织的共定位荧光成像和 Western blot，我们证实了 NO 的释放激活了 TME 中金属蛋白酶的表达，并进一步降解了肿瘤周边区域的胶原 I，从而消除了脂质体渗透的屏障。由于肿瘤内部脂质体的积累增强，实现了近红外二区成像引导的 PTT，并具有显著的治疗效果。
