Cho Hyunah, Cho Clifford S, Indig Guilherme L, Lavasanifar Afsaneh, Vakili Mohammad Reza, Kwon Glen S
Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, Wisconsin, United States of America.
Section of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, Wisconsin, United States of America.
PLoS One. 2014 Feb 26;9(2):e89968. doi: 10.1371/journal.pone.0089968. eCollection 2014.
In a two-step strategy, an intraperitoneal (IP) injection of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) micelles containing paclitaxel (PTX), cyclopamine (CYP), and gossypol (GSP) at 30, 30, and 30 mg/kg, respectively, debulked tumor tissues by 1.3-fold, based on loss of bioluminescence with <10% body weight change, and induced apoptosis in peritoneal tumors when used as neoadjuvant chemotherapy (NACT) in an ES-2-luc-bearing xenograft model for ovarian cancer. In a second step, a single intravenous (i.v.) injection of apoptosis-targeting GFNFRLKAGAKIRFGS-PEG-b-PCL micelles containing a near-infrared (NIR) fluorescence probe, DiR (1,1'-dioctadecyltetramethyl indotricarbocyanine iodide), resulted in increased peritoneal DiR accumulation in apoptosis-induced ES-2-luc tumor tissues (ex vivo) by 1.5-fold compared with DiR molecules delivered by methoxy PEG-b-PCL micelles (non-targeted) at 48 h after i.v. injection in a second step. As a result, a tandem of PEG-b-PCL micelles enabled high-resolution detection of ca. 1 mm diameter tumors, resulting in resection of approximately 90% of tumors, and a low peritoneal cancer index (PCI) of ca. 7. Thus, a tandem of PEG-b-PCL micelles used for NCAT and NIR fluorescence imaging of therapy-induced apoptosis for intraoperative surgical guidance may be a promising treatment strategy for metastatic ovarian cancer.
在两步策略中，腹腔内（IP）注射分别含有紫杉醇（PTX）、环杷明（CYP）和棉酚（GSP）的聚（乙二醇）-嵌段-聚（ε-己内酯）（PEG-b-PCL）胶束，剂量分别为30、30和30mg/kg，基于生物发光损失且体重变化<10%，肿瘤组织体积缩小了1.3倍，并且在用于卵巢癌ES-2-luc荷瘤异种移植模型的新辅助化疗（NACT）时，可诱导腹膜肿瘤细胞凋亡。第二步，单次静脉内（i.v.）注射含有近红外（NIR）荧光探针DiR（1,1'-二辛基四甲基吲哚三碳菁碘化物）的靶向凋亡GFNFRLKAGAKIRFGS-PEG-b-PCL胶束，与静脉注射第二步48小时后由甲氧基PEG-b-PCL胶束（非靶向）递送的DiR分子相比，凋亡诱导的ES-2-luc肿瘤组织（体外）中的腹膜DiR积累增加了1.5倍。结果，串联的PEG-b-PCL胶束能够对直径约1mm的肿瘤进行高分辨率检测，从而切除约90%的肿瘤，且腹膜癌指数（PCI）约为7。因此，用于新辅助化疗和近红外荧光成像以术中指导治疗诱导凋亡的串联PEG-b-PCL胶束可能是转移性卵巢癌的一种有前景的治疗策略。
