Wang Dali, Tu Chunlai, Su Yue, Zhang Chuan, Greiser Udo, Zhu Xinyuan, Yan Deyue, Wang Wenxin
School of Chemistry and Chemical Engineering , State Key Laboratory of Metal Matrix Composites , Shanghai Jiao Tong University , 800 Dongchuan Road , Shanghai 200240 , People's Republic of China . Email:
Charles Institute of Dermatology , School of Medicine and Medical Science , University College Dublin , Belfield , Dublin 4 , Ireland . Email:
Chem Sci. 2015 Jul 1;6(7):3775-3787. doi: 10.1039/c5sc01188d. Epub 2015 May 12.
Despite of great advances of phospholipids and liposomes in clinical therapy, very limited success has been achieved in the preparation of smart phospholipids and controlled-release liposomes for drug delivery and clinical trials. Here we report a supramolecular approach to synthesize novel supramolecularly engineered phospholipids based on complementary hydrogen bonding of nucleosides, which greatly reduces the need of tedious chemical synthesis, including reducing the strict requirements for multistep chemical reactions, and the purification of the intermediates and the amount of waste generated relative more traditional approaches. These upgraded phospholipids self-assemble into liposome-like bilayer structures in aqueous solution, exhibiting fast stimuli-responsive ability due to the hydrogen bonding connection. and evaluations show the resulted supramolecular liposomes from nucleoside phospholipids could effectively transport drug into tumor tissue, rapidly enter tumor cells, and controllably release their payload in response to an intracellular acidic environment, thus resulting in a much higher antitumor activity than conventional liposomes. The present supramolecularly engineered phospholipids represent an important evolution in comparison to conventional covalent-bonded phospholipid systems.
尽管磷脂和脂质体在临床治疗方面取得了巨大进展，但在制备用于药物递送和临床试验的智能磷脂和控释脂质体方面，取得的成功非常有限。在此，我们报告一种超分子方法，基于核苷的互补氢键作用合成新型超分子工程磷脂，这大大减少了繁琐化学合成的需求，包括降低了对多步化学反应的严格要求、中间体的纯化以及相对于传统方法产生的废物量。这些升级后的磷脂在水溶液中自组装成脂质体样双层结构，由于氢键连接而表现出快速的刺激响应能力。评估表明，由核苷磷脂产生的超分子脂质体可以有效地将药物输送到肿瘤组织中，迅速进入肿瘤细胞，并响应细胞内酸性环境可控地释放其负载物，从而产生比传统脂质体更高的抗肿瘤活性。与传统的共价键合磷脂系统相比，目前的超分子工程磷脂代表了一个重要的进展。
