Chang Ji-Eun, Cho Hyun-Jong, Jheon Sanghoon
Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital.
College of Pharmacy, Kangwon National University.
J Vis Exp. 2016 Dec 1(118):54865. doi: 10.3791/54865.
Photodynamic therapy (PDT) is a non-invasive and non-surgical method representing an attractive alternative choice for lung cancer treatment. Photosensitizers selectively accumulate in tumor tissue and lead to tumor cell death in the presence of oxygen and the proper wavelength of light. To increase the therapeutic effect of PDT, we developed both photosensitizer- and anticancer agent-loaded lung cancer-targeted nanoparticles. Both enhanced permeability and retention (EPR) effect-based passive targeting and hyaluronic-acid-CD44 interaction-based active targeting were applied. CD44 is a well-known hyaluronic acid receptor that is often introduced as a biomarker of non-small cell lung cancer. In addition, a combination of PDT and chemotherapy is adopted in the present study. This combination concept may increase anticancer therapeutic effects and reduce adverse reactions. We chose hypocrellin B (HB) as a novel photosensitizer in this study. It has been reported that HB causes higher anticancer efficacy of PDT compared to hematoporphyrin derivatives. Paclitaxel was selected as the anticancer drug since it has proven to be a potential treatment for lung cancer. The antitumor efficacies of photosensitizer (HB) solution, photosensitizer encapsulated hyaluronic acid-ceramide nanoparticles (HB-NPs), and both photosensitizer- and anticancer agent (paclitaxel)-encapsulated hyaluronic acid-ceramide nanoparticles (HB-P-NPs) after PDT were compared both in vitro and in vivo. The in vitro phototoxicity in A549 (human lung adenocarcinoma) cells and the in vivo antitumor efficacy in A549 tumor-bearing mice were evaluated. The HB-P-NP treatment group showed the most effective anticancer effect after PDT. In conclusion, the HB-P-NPs prepared in the present study represent a potential and novel photosensitizer delivery system in treating lung cancer with PDT.
光动力疗法（PDT）是一种非侵入性和非手术方法，是肺癌治疗的一种有吸引力的替代选择。光敏剂在肿瘤组织中选择性积聚，并在有氧气和适当波长的光存在的情况下导致肿瘤细胞死亡。为了提高PDT的治疗效果，我们开发了负载光敏剂和抗癌剂的肺癌靶向纳米颗粒。同时应用了基于增强渗透和滞留（EPR）效应的被动靶向和基于透明质酸-CD44相互作用的主动靶向。CD44是一种著名的透明质酸受体，常被用作非小细胞肺癌的生物标志物。此外，本研究采用了PDT与化疗相结合的方法。这种联合概念可能会提高抗癌治疗效果并减少不良反应。在本研究中，我们选择竹红菌素B（HB）作为新型光敏剂。据报道，与血卟啉衍生物相比，HB在PDT中具有更高的抗癌疗效。由于紫杉醇已被证明是肺癌的一种潜在治疗药物，因此被选为抗癌药物。比较了光敏剂（HB）溶液、包载光敏剂的透明质酸-神经酰胺纳米颗粒（HB-NPs）以及同时包载光敏剂和抗癌剂（紫杉醇）的透明质酸-神经酰胺纳米颗粒（HB-P-NPs）在PDT后的体外和体内抗肿瘤疗效。评估了A549（人肺腺癌）细胞的体外光毒性和A549荷瘤小鼠的体内抗肿瘤疗效。HB-P-NP治疗组在PDT后显示出最有效的抗癌效果。总之，本研究制备的HB-P-NPs是一种在PDT治疗肺癌中具有潜力的新型光敏剂递送系统。
