School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA.
Department of Pathology, Louisiana State University Health Sciences Center, 1501 Kings Hwy, Shreveport, LA 71103, USA.
Int J Pharm. 2022 Jan 25;612:121364. doi: 10.1016/j.ijpharm.2021.121364. Epub 2021 Dec 9.
Cancer treatment faces the challenge of selective delivery of the cytotoxic drug to the desired site of action to minimize undesired side effects. The liposomal formulation containing targeting ligand conjugated cytotoxic drug can be an effective approach to specifically deliver chemotherapeutic drugs to cancer cells that overexpress a particular cell surface receptor. This research focuses on the in vitro and in vivo studies of a peptidomimetic ligand attached doxorubicin for the HER2 positive lung and breast cancer cells transported by a pH-dependent liposomal formulation system for the enhancement of targeted anticancer treatment. The selected pH-sensitive liposome formulation showed effective pH-dependent delivery of peptidomimetic-doxorubicin conjugate at lower pH conditions mimicking tumor microenvironment (pH-6.5) compared to normal physiological conditions (pH 7.4), leading to the improvement of cell uptake. In vivo results revealed the site-specific delivery of the formulation and enhanced antitumor activity with reduced toxicity compared to the free doxorubicin (Free Dox). The results suggested that the targeting ligand conjugated cytotoxic drug with the pH-sensitive liposomal formulation is a promising approach to chemotherapy.
癌症治疗面临的挑战是将细胞毒性药物选择性地递送到所需的作用部位，以最小化不良反应。含有靶向配体连接的细胞毒性药物的脂质体制剂可以是一种将化疗药物特异性递送到过表达特定细胞表面受体的癌细胞的有效方法。这项研究集中于通过 pH 依赖性脂质体制剂系统对 HER2 阳性肺癌和乳腺癌细胞进行转导的肽模拟配体连接阿霉素的体外和体内研究，以增强靶向抗癌治疗。与正常生理条件（pH7.4）相比，所选 pH 敏感脂质体制剂在模拟肿瘤微环境（pH6.5）的较低 pH 条件下显示出肽模拟物-阿霉素缀合物的有效 pH 依赖性递药，从而提高了细胞摄取。体内结果表明，与游离阿霉素（Free Dox）相比，该制剂具有更好的肿瘤靶向性和抗肿瘤活性，同时降低了毒性。结果表明，靶向配体连接的细胞毒性药物与 pH 敏感脂质体制剂是一种有前途的化疗方法。
