School of Clinical Dentistry, Unit of Oral & Maxillofacial Medicine & Surgery, University of Sheffield, Sheffield, UK.
Nanomedicine (Lond). 2010 Sep;5(7):1025-36. doi: 10.2217/nnm.10.97.
The prognosis for oral squamous cell carcinoma (OSCC) is not improving despite advances in surgical treatment. As with many cancers, there is a need to deliver therapeutic agents with greater efficiency into OSCC to improve treatment and patient outcome. The development of polymersomes offers a novel way to deliver therapy directly into tumor cells. Here we examined the internalization and biodistribution of two different fluorescently labeled polymersome formulations; polyethylene oxide (PEO)-poly 2-(diisopropylamino)ethyl methacrylate (PDPA) and poly 2-(methacryloyloxy)ethyl phosphorylcholine (PMPC)-PDPA, into SCC4 OSCC cells in vitro and in vivo. In vitro SCC4 monolayers internalized PMPC-PDPA and PEO-PDPA at similar rates. However, in vivo PMPC-PDPA polymersomes penetrated deeper and were more widely dispersed in SCC4 tumors than PEO-PDPA polymersomes. In the liver and spleen PMPC-PDPA mainly accumulated in tissue macrophages. However, in tumors PMPC-PDPA was found extensively in the nucleus and cytoplasm of tumor cells as well as in tumor-associated macrophages. Use of PMPC-PDPA polymersomes may enhance polymersome-mediated antitumor therapy.
口腔鳞状细胞癌 (OSCC) 的预后尽管在手术治疗方面取得了进展,但仍未得到改善。与许多癌症一样,需要更有效地将治疗剂递送到 OSCC 中,以改善治疗效果和患者预后。聚合物囊泡的开发为直接将治疗剂递送到肿瘤细胞提供了一种新方法。在这里,我们研究了两种不同荧光标记聚合物囊泡制剂;聚环氧乙烷 (PEO)-聚 2-(二异丙基氨基)乙基甲基丙烯酸酯 (PDPA) 和聚 2-(甲基丙烯酰氧基)乙基磷酸胆碱 (PMPC)-PDPA,在体外和体内进入 SCC4 OSCC 细胞的内化和体内分布。在体外 SCC4 单层细胞以相似的速度内化 PMPC-PDPA 和 PEO-PDPA。然而,在体内,PMPC-PDPA 聚合物囊泡比 PEO-PDPA 聚合物囊泡渗透得更深,在 SCC4 肿瘤中的分布也更广。在肝脏和脾脏中,PMPC-PDPA 主要积聚在组织巨噬细胞中。然而,在肿瘤中,PMPC-PDPA 广泛存在于肿瘤细胞的核和细胞质以及肿瘤相关巨噬细胞中。使用 PMPC-PDPA 聚合物囊泡可能会增强聚合物囊泡介导的抗肿瘤治疗。