Wuya College of Innovation, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
Int J Pharm. 2019 May 1;562:313-320. doi: 10.1016/j.ijpharm.2019.03.037. Epub 2019 Mar 18.
Photosensitizer-based photodynamic therapy (PDT) has attracted great attention in cancer treatment. However, achieving efficient delivery of photosensitizers is still a great challenge for their clinical applications. The photosensitizer-encapsulating delivery nanosystem usually suffers from poor stability, complex preparation process and low drug loading. Herein, we utilize a surfactant-like chemotherapeutic agent, mitoxantrone (MTX), as a nanocarrier to deliver a photosensitizer pyropheophorbide a (PPa) for antitumor therapy. MTX consists of aromatic rings (hydrophobic part) and two amino-groups and two hydroxyl-groups (hydrophilic part) with planar structure, which could interact with PPa via π-π stacking, hydrophobic interactions, intermolecular hydrogen bonding and electrostatic interactions. This system (PPa@MTX) spontaneously forms near-spherical nanostructures (∼150 nm), has a high loading capacity for PPa (56.5%) and exhibits a pH-responsive drug release manner in vitro. In vivo antitumor efficacy evaluations show that the pegylated PPa@MTX nanosystem has increased accumulation in tumor tissues and enhanced antitumor efficacy in female BALB/c mice bearing murine mammary carcinoma (4T1) tumor cells, compared to free PPa. Employing the surfactant-like drug as nanocarriers, our results show that the "drug-delivering-drug" strategy is a good foundation for the development of novel PDT-based drug delivery system against cancer.
基于光敏剂的光动力疗法（PDT）在癌症治疗中引起了极大的关注。然而，实现光敏剂的高效递送仍然是其临床应用的一大挑战。封装光敏剂的递送纳米系统通常存在稳定性差、制备过程复杂和载药量低等问题。在这里，我们利用一种类似表面活性剂的化疗药物米托蒽醌（MTX）作为纳米载体来递送光敏剂原卟啉 IX（PPa）进行抗肿瘤治疗。MTX 由芳香环（疏水部分）和两个氨基及两个羟基（亲水部分）组成，具有平面结构，可通过π-π 堆积、疏水相互作用、分子间氢键和静电相互作用与 PPa 相互作用。该系统（PPa@MTX）自发形成近球形纳米结构（∼150nm），对 PPa 具有高载药能力（56.5%），并在体外表现出 pH 响应性药物释放方式。体内抗肿瘤疗效评价表明，与游离 PPa 相比，聚乙二醇化的 PPa@MTX 纳米系统在荷有 4T1 肿瘤细胞的雌性 BALB/c 小鼠肿瘤组织中的积累增加，抗肿瘤疗效增强。利用类似表面活性剂的药物作为纳米载体，我们的结果表明，“载药-药物”策略为开发新型基于 PDT 的抗癌药物递送系统奠定了良好的基础。
