Department of Pharmaceutics, Daqing Campus, Harbin Medical University, Key Laboratory of Research and Development of Natural Products at Harbin Medical University, 39 Xin Yang Road, Daqing 163319, China.
Department of Pharmaceutical Engineering, China Pharmaceutical University, 639 Longmian Rd, Nanjing 211198, China.
Eur J Pharm Biopharm. 2022 Oct;179:206-220. doi: 10.1016/j.ejpb.2022.09.012. Epub 2022 Sep 21.
Hepatocellular carcinoma (HCC) is a most common primary liver cancer among the most deadly malignancies. Selectively killing the cancer cells within the liver urgently requires the novel treatment strategies. The combination of sonodynamic therapy (SDT) and chemotherapy based on the nanotechnology have achieved some achievements in the HCC treatments. However, off-targeting drug delivery to healthy cells and the hypoxic microenvironment in the solid tumors frustrate the efforts to the combined strategy. The hypoxic microenvironment restrains the generation of ROS, leading to the decreased effects of SDT. To improve the clinical outcomes of chemo/SDT strategy, we created a novel oxygen self-enriched active targeted nanovesicle (ICG-DOX NPs/PFH@SP94-Lip). SP94 peptide could enhance the selectivity of the nanovesicles to liver tumor cells rather than normal liver cells. Besides, an oxygen carrier, perfluorohexanes (PFH), was co-loaded into liposomes to increase the oxygen level in tumor tissue, thus improving the effects of SDT. The in vivo studies showed that the ICG-DOX NPs/PFH@SP94-Lip combined with the external US stimulation significantly inhibited effects on tumor growth. Therefore, this novel oxygen self-enriched chemo/SDT nanocomposites represents a proof-of-concept liver tumor treatment strategy.
肝细胞癌（HCC）是最常见的原发性肝癌，也是最致命的恶性肿瘤之一。迫切需要新的治疗策略来选择性地杀死肝脏内的癌细胞。基于纳米技术的声动力学疗法（SDT）和化疗的联合已经在 HCC 治疗中取得了一些成果。然而，药物靶向非肿瘤细胞和实体瘤中的缺氧微环境阻碍了联合策略的发展。缺氧微环境抑制了 ROS 的产生，导致 SDT 效果降低。为了提高化疗/SDT 策略的临床效果，我们构建了一种新型的氧自富活性靶向纳米囊泡（ICG-DOX NPs/PFH@SP94-Lip）。SP94 肽可以增强纳米囊泡对肝癌细胞的选择性，而不是正常肝细胞。此外，载氧剂全氟己烷（PFH）被共载入脂质体中，以增加肿瘤组织中的氧水平，从而提高 SDT 的效果。体内研究表明，ICG-DOX NPs/PFH@SP94-Lip 联合外部超声刺激显著抑制了肿瘤生长。因此，这种新型的氧自富化疗/SDT 纳米复合材料代表了一种肝癌治疗的概念验证策略。
