Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models
Cell-Membrane Coated Nanoparticles for Tumor Delineation and Qualitative Estimation of Cancer Biomarkers at Single Wavelength Excitation in Murine and Phantom Models
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DOI：
10.1021/acsnano.3c00578
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发表时间：
2023-04-26
期刊：
影响因子：
17.1
通讯作者：
Gruev，Viktor
中科院分区：
文献类型：
--
作者：
Srivastava，Indrajit;Lew，Benjamin;Gruev，Viktor
通过荧光成像的实时指导改善了肿瘤切除的手术结果，减少了留下阳性边缘的机会。由于肿瘤是异质性的，因此必须以高灵敏度和特异性询问多种过表达的癌症生物标志物以改善手术结果。然而，为了准确的肿瘤描绘和肿瘤生物标志物的比率检测，当前的方法需要多个激发波长来对多个生物标志物成像，这在临床环境中是不切实际的。在这里，我们开发了一种仿生平台，包括具有红细胞膜（RBC）涂层的近红外荧光半导体聚合物纳米颗粒（SPN），能够在手术干预期间使用单一激发波长靶向两种代表性细胞表面生物标志物（叶酸、α β3整联蛋白）用于肿瘤描绘。我们在玻璃体肿瘤细胞、离体肿瘤模拟模型和小鼠异种移植肿瘤模型中评估了我们的单激发比率纳米颗粒。有利的生物学特性（改善的生物相容性、延长的血液循环、减少的肝脏摄取）由上级光谱特征补充：（i）在体内样品中具有高肿瘤与正常组织（T/NT）比率的肿瘤区域中的特异性荧光增强和（ii）用单波长激发估计细胞表面肿瘤生物标志物，提供关于癌症进展（转移）的见解。我们的单激励双输出方法有可能区分肿瘤和健康区域，同时提供癌症进展的定性指标，从而指导手术室的外科医生进行切除手术。
Real-time guidance through fluorescence imaging improves the surgical outcomes of tumor resections, reducing the chances of leaving positive margins behind. As tumors are heterogeneous, it is imperative to interrogate multiple overexpressed cancer biomarkers with high sensitivity and specificity to improve surgical outcomes. However, for accurate tumor delineation and ratiometric detection of tumor biomarkers, current methods require multiple excitation wavelengths to image multiple biomarkers, which is impractical in a clinical setting. Here, we have developed a biomimetic platform comprising near-infrared fluorescent semiconducting polymer nanoparticles (SPNs) with red blood cell membrane (RBC) coating, capable of targeting two representative cell-surface biomarkers (folate, αυβ3 integrins) using a single excitation wavelength for tumor delineation during surgical interventions. We evaluate our single excitation ratiometric nanoparticles inin vitrotumor cells,ex vivotumor-mimicking phantoms, andin vivomouse xenograft tumor models. Favorable biological properties (improved biocompatibility, prolonged blood circulation, reduced liver uptake) are complemented by superior spectral features: (i) specific fluorescence enhancement in tumor regions with high tumor-to-normal tissue (T/NT) ratios inex vivosamples and (ii) estimation of cell-surface tumor biomarkers with single wavelength excitation providing insights about cancer progression (metastases). Our single excitation, dual output approach has the potential to differentiate between the tumor and healthy regions and simultaneously provide a qualitative indicator of cancer progression, thereby guiding surgeons in the operating room with the resection process.