Preclinical Evaluation and Monitoring of the Therapeutic Response of a Dual Targeted Hyaluronic Acid Nanodrug.

Preclinical Evaluation and Monitoring of the Therapeutic Response of a Dual Targeted Hyaluronic Acid Nanodrug.
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双靶向透明质酸纳米药物的临床前评估和治疗反应监测

DOI:
10.1155/2017/4972701
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发表时间:
2017
影响因子:
--
通讯作者:
Gao S
Gao S
中科院分区:
医学4区
文献类型:
--
作者:
Chen M;Zhang W;Yuan K;Bo M;Chen B;Li L;Ma Q;Zhu L;Gao S

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化疗是一种有效的癌症治疗方法,但生物相容性差,缺乏肿瘤靶向。在这里,我们通过将10-羟基喜树碱(HCPT)封装到透明质酸纳米颗粒(HANP)中来开发用于靶向癌症治疗的CD 44靶向聚合物纳米复合物。在体外,与游离HCPT相比,HANP/HCPT显示出对五种癌细胞系(包括HT 29、A549、MDA-MB-231、HepG 2和MDA-MB-435)的改善的细胞毒性。在MDA-MB-231乳腺癌异种移植物中全身给药后,相对于未给药组,HANP/HCPT给药组中的肿瘤生长被显著抑制5.25 ± 0.21倍。此外,还通过18 F-氟-2-脱氧-D-葡萄糖([18 F] FDG)正电子发射断层扫描(PET)评估并确认了治疗反应。MDA-MB-231肿瘤在首次治疗后7天对HANP/HCPT有反应,这有利于治疗策略的调整和个性化。在用HANP/HCPT处理的小鼠中未观察到明显的全身毒性作用。总之,HANPs作为癌症化疗的靶向药物载体具有很大的前景。我们的HANP平台还可以提供其他疏水性化疗药物。
Chemotherapy is a powerful cancer treatment but suffers from poor biocompatibility and a lack of tumor targeting. Here, we developed a CD44-targeted polymeric nanocomplex by encapsulating 10-hydroxycamptothecin (HCPT) into hyaluronic acid nanoparticles (HANP) for targeted cancer therapy. In vitro, the HANP/HCPT showed improved cytotoxicity to five cancer cell lines including HT29, A549, MDA-MB-231, HepG2, and MDA-MB-435 versus free HCPT. After systemic administration into MDA-MB-231 breast cancer xenograft, tumor growth was significantly inhibited 5.25 ± 0.21 times in the HANP/HCPT treated group relative to the nontreated group. In addition, the treatment response was also accessed and confirmed by 18F-fluoro-2-deoxy-D-glucose ([18F] FDG) positron emission tomography (PET). The MDA-MB-231 tumors responded to HANP/HCPT 7 days after the first treatment, which benefits treatment strategy adjustment and personalization. No apparent systemic toxic effects were seen in mice treated with HANP/HCPT. In summary, the HANPs have great promise as a targeted drug carrier for cancer chemotherapy. Our HANP platform can also deliver other hydrophobic chemotherapy agents.
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