Novel therapy modalities combining photodynamic therapy and liposomal cisplatin for pancreatic cancer treatments

Jia-Haur Chen , John Vincent Lim , Yih-Chih Hsu
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Abstract

Combination therapy is the mainstream cancer treatment to achieve the best clinical benefits for patients. Photodynamic therapy (PDT) can improve vascular permeability and enhance nanoparticle uptake in tumors with drug delivery permeability and retention effects. PDT can also minimize tissue damage compared with traditional chemotherapy. Therefore, it is beneficial to use PDT with chemotherapeutic administrations to obtain these benefits. Cisplatin (CDDP) is a widely used chemotherapeutic drug with strong toxic side effects such as nephrotoxicity and neurotoxicity. Our novel study is the first original study to investigate PDT with novel lipid-platinum chloride (LPC) nanoparticles to prove the results of greater efficacy and minimal side effects. In the in vitro study, CDDP and LPC nanoparticles enhanced higher amounts of cell death as the concentration increased. The treatment effects of PDT+LPC NPs using pancreatic MIAPaCa-2 and PANC-1 tumor models revealed that PDT+LPC significantly inhibited tumor growth. The body weight of all animals increased with animals showing no side effects. IHC assays for Ki-67, CD31, and cleaved caspase-3, TUNEL assays and western blot assays showed consistent results. Collectively, the combined PDT with LPC nanoparticles showed significant therapeutic outcomes with promising potential for clinical applications.

Abstract Image

结合光动力疗法和顺铂脂质体治疗胰腺癌的新疗法
联合治疗是使患者获得最佳临床效益的主流癌症治疗方法。光动力疗法(PDT)可以改善肿瘤血管通透性,增强纳米颗粒的摄取,具有药物传递的通透性和滞留作用。与传统化疗相比,PDT还可以将组织损伤降到最低。因此,将PDT与化疗一起使用是有益的,以获得这些益处。顺铂(Cisplatin, CDDP)是一种应用广泛的化疗药物,具有肾毒性和神经毒性等强烈毒副作用。我们的新研究是第一个用新型脂质-氯化铂(LPC)纳米颗粒研究PDT的原始研究,以证明更大的疗效和最小的副作用。在体外研究中,随着CDDP和LPC纳米颗粒浓度的增加,细胞死亡的数量增加。PDT+LPC NPs对胰腺MIAPaCa-2和PANC-1肿瘤模型的治疗效果显示,PDT+LPC显著抑制肿瘤生长。所有动物的体重都增加了,而且没有出现任何副作用。Ki-67、CD31和cleaved caspase-3的IHC检测、TUNEL检测和western blot检测结果一致。总的来说,PDT联合LPC纳米颗粒显示出显著的治疗效果,具有良好的临床应用潜力。
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