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ACS Appl Mater Interfaces:发现新一代肿瘤靶向药物载体

2019-02-13 郝俊 中山大学

近日,中山大学附属口腔医院生物医疗团队汪华教授和生命科学学院张雁教授合作,在美国化学学会期刊ACS Appl. Mater. Interfaces上发表题为“New Cell-Penetrating Peptide (KRP) with Multiple Physicochemical Properties Endows Doxorubicin with Tumor Targeting and I

近日,中山大学附属口腔医院生物医疗团队汪华教授和生命科学学院张雁教授合作,在美国化学学会期刊ACS Appl. Mater. Interfaces上发表题为“New Cell-Penetrating Peptide (KRP) with Multiple Physicochemical Properties Endows Doxorubicin with Tumor Targeting and Improves Its Therapeutic Index”的论文,他们发现了一种新型细胞渗透肽KRP,可引导化疗药物精准靶标肿瘤组织,有效改善抗癌效率。

研制具有像导弹一样有精准靶向能力的抗癌药物是药物开发的终极目标,目前常用的研发策略是抗体-细胞毒轭合药。自2000年吉妥珠单抗药批准以来,已经有六十多个抗体-细胞毒轭合药进入临床研究阶段。近年来,渗透肽作为新一代药物载体备受国内外关注,但是因其缺乏肿瘤靶向性,并容易被溶酶体水解而很少进入临床研究。


肿瘤靶向药物载体以KRP-DOX复合物形式运送阿霉素进入肿瘤细胞和对照阿霉素被动扩散过程

该研究发现的新型细胞渗透肽KRP,可通过稳定的共价键结合细胞毒性抗癌药物阿霉素(DOX), 形成复合体KRP-DOX。在血液循环中,带有较多正电荷的KRP能与肿瘤细胞膜负电荷发生静电结合,有利于肿瘤细胞摄取KRP,从而携带DOX定向运送并蓄积到肿瘤组织中,进入肿瘤细胞质和细胞核,达到杀伤肿瘤细胞的目的。同时,KRP-DOX很少被细胞内溶酶体破坏。肿瘤负荷的动物实验显示,KRP-DOX显着改善了肿瘤治疗效率,明显减少了对心脏等正常组织细胞的损伤,且毒副作用低。此外,与抗体策略相比,KRP分子量小(6.4道尔顿),不需要动物即可规模化生产,质量容易控制,制造成本低,而且无异种蛋白的免疫反应风险,因此具有较好的开发和应用前景。

该研究工作得到国家”863计划”,广东省重大科技计划和国家自然科学基金的大力支持。

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    2019-10-09 shanyongle
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    2020-01-27 mei539
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    2019-02-15 yaanren
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