Nanoparticles have garnered widespread interest for both the imaging and treatment of cancer due to their unique and tunable pharmacokinetics and their ability to carry a high payload of diverse compounds. However, despite these favorable attributes, the extent of tumor accumulation can be severely restricted due to the dense stroma surrounding the often-permeable blood vessel wall and high intratumoral pressure. In this study, we investigated whether modifying the surface of pegylated gold nanoparticles (AuNPs) with collagenase could improve the accumulation of nanoparticles within a murine tumor xenograft. It was determined that collagenase remains active after surface conjugation and the presence of collagenase has no measureable effect on cell proliferation in vitro. Following intravenous injection, the largest fractions of collagenase-labeled AuNPs were found in the liver and spleen. Histological analysis revealed no signs of toxicity in either of these organs. Blood chemistry revealed normal levels of liver enzymes, but a slightly elevated level of total bilirubin. Within the tumor, AuNPs labeled with collagenase exhibited a 35% increase in accumulation compared with unlabeled AuNPs. Therefore, these studies provide preliminary evidence that the functionalization of nanoparticles with collagenase represent an effective and safe approach to improve tumor accumulation.

中文翻译：

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用胶原酶功能化的纳米颗粒在小鼠异种移植模型中表现出改善的肿瘤积累

纳米颗粒由于其独特且可调节的药代动力学以及携带多种化合物的高负载能力而在癌症成像和治疗方面引起了广泛关注。然而，尽管有这些有利的属性，但由于围绕通常可渗透的血管壁的致密基质和高肿瘤内压，肿瘤积聚的程度可能受到严重限制。在这项研究中，我们研究了用胶原酶修饰聚乙二醇化金纳米粒子 (AuNPs) 的表面是否可以改善纳米粒子在鼠肿瘤异种移植物中的积累。确定胶原酶在表面缀合后保持活性，并且胶原酶的存在对体外细胞增殖没有可测量的影响。静脉注射后，在肝脏和脾脏中发现了最大部分的胶原酶标记的 AuNP。组织学分析显示这些器官中的任何一个都没有毒性迹象。血液化学显示肝酶水平正常，但总胆红素水平略有升高。在肿瘤内，与未标记的 AuNPs 相比，用胶原酶标记的 AuNPs 的积累增加了 35%。因此，这些研究提供了初步证据，证明纳米颗粒与胶原酶的功能化代表了一种有效且安全的改善肿瘤积累的方法。与未标记的 AuNPs 相比，用胶原酶标记的 AuNPs 的积累增加了 35%。因此，这些研究提供了初步证据，证明纳米颗粒与胶原酶的功能化代表了一种有效且安全的改善肿瘤积累的方法。与未标记的 AuNPs 相比，用胶原酶标记的 AuNPs 的积累增加了 35%。因此，这些研究提供了初步证据，证明纳米颗粒与胶原酶的功能化代表了一种有效且安全的改善肿瘤积累的方法。