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载姜黄素 B 的叶酸偶联聚合物胶束用于卵巢癌的腹腔靶向给药：体内外研究。

Hypocrellin B-loaded, folate-conjugated polymeric micelle for intraperitoneal targeting of ovarian cancer in vitro and in vivo.

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.

Gynecology Oncology Key Laboratory, Qilu Hospital, Shandong University, Jinan, China.

出版信息

Cancer Sci. 2018 Jun;109(6):1958-1969. doi: 10.1111/cas.13605. Epub 2018 May 7.

DOI:10.1111/cas.13605
PMID:29617063
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5989858/
Abstract

Photodynamic therapy (PDT) is considered an innovative and attractive modality to treat ovarian cancer. In the present study, a biodegradable polymer poly (ethylene glycol) (PEG)-poly (lactic acid)(PLA)-folate (FA-PEG-PLA) was prepared in order to synthesize an active-targeting, water-soluble and pharmacomodulated photosensitizer nanocarrier. Drug-loading content, encapsulation efficiency, in vitro and in vivo release were characterized, in which hypocrellin B (HB)/FA-PEG-PLA micelles had a high encapsulation efficiency and much slower control release for drugs compared to free drugs (P < .05). To evaluate the targeting ability of the HB/FA-PEG-PLA micelles, a cellular uptake study in vitro was carried out, which showed significantly enhanced uptake of HB/FA-PEG-PLA micelles in SKOV3 (FR+) compared to A2780 cancer cells (FR-). The enhanced uptake of HB/FA-PEG-PLA micelles to cancer cells resulted in a more effective post-PDT killing of SKOV3 cells compared to plain micelles and free drugs. Binding and uptake of HB/FA-PEG-PLA micelles by SKOV3 cells were also observed in vivo after ip injection of folate-targeted micelles in tumor-bearing ascitic ovarian cancer animals. Drug levels in ascitic tumor tissues were increased 20-fold (P < .001), which underscored the effect of a regional therapy approach with folate targeting. Furthermore, the HB-loaded micelles were mainly distributed in kidney and liver (the main clearance organs) in biodistribution. These results showed that our newly developed PDT photosensitizer HB/FA-PEG-PLA micelles have a high drug-loading capacity, good biocompatibility, controlled drug release, and enhanced targeting and antitumor effect, which is a potential approach to future targeting ovarian cancer therapy.

摘要

光动力疗法（PDT）被认为是治疗卵巢癌的一种创新且有吸引力的方法。在本研究中，制备了一种可生物降解的聚合物聚乙二醇（PEG）-聚乳酸（PLA）-叶酸（FA-PEG-PLA），以合成一种主动靶向、水溶性和药物调节的光敏剂纳米载体。对载药含量、包封效率、体外和体内释放进行了表征，其中竹红菌素 B（HB）/FA-PEG-PLA 胶束具有较高的载药效率和比游离药物慢得多的药物控制释放（P<.05）。为了评估 HB/FA-PEG-PLA 胶束的靶向能力，进行了体外细胞摄取研究，结果表明 HB/FA-PEG-PLA 胶束在 SKOV3（FR+）中的摄取明显高于 A2780 癌细胞（FR-）。HB/FA-PEG-PLA 胶束对癌细胞的摄取增强导致 SKOV3 细胞的 PDT 后杀伤效果比普通胶束和游离药物更有效。在荷瘤腹水卵巢癌动物中腹腔注射叶酸靶向胶束后，也观察到 HB/FA-PEG-PLA 胶束在 SKOV3 细胞中的结合和摄取。腹水肿瘤组织中的药物水平增加了 20 倍（P<.001），这突显了叶酸靶向区域治疗方法的效果。此外，载药胶束主要分布在肾脏和肝脏（主要清除器官）中。这些结果表明，我们新开发的 PDT 光敏剂 HB/FA-PEG-PLA 胶束具有高载药能力、良好的生物相容性、药物控制释放以及增强的靶向和抗肿瘤效果，是未来靶向卵巢癌治疗的一种潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/44054f9a60d6/CAS-109-1958-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/71109141e016/CAS-109-1958-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/00064997b495/CAS-109-1958-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/e533c2714084/CAS-109-1958-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/9db22e748c91/CAS-109-1958-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/c6ee409a1ad5/CAS-109-1958-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/b80e0339827c/CAS-109-1958-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/44054f9a60d6/CAS-109-1958-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/71109141e016/CAS-109-1958-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/00064997b495/CAS-109-1958-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/e533c2714084/CAS-109-1958-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/9db22e748c91/CAS-109-1958-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/c6ee409a1ad5/CAS-109-1958-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/b80e0339827c/CAS-109-1958-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5b2/5989858/44054f9a60d6/CAS-109-1958-g007.jpg

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