Cancer Institute, Longhua Hospital Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, China.
Cancer Institute, Longhua Hospital Shanghai University of Traditional Chinese Medicine, 725 Wanping South Road, Shanghai, 200032, China.
Colloids Surf B Biointerfaces. 2019 Oct 1;182:110325. doi: 10.1016/j.colsurfb.2019.06.055. Epub 2019 Jul 2.
Targeting modifications and smart responsiveness of nanomedicines can enable anticancer drugs to be selectively delivered to and controllably released in tumour cells or tissues, which can reduce the treatment's toxicity and side effects. Good biocompatibility is crucial for the clinical application of any nanomedicine. In this study, a double-targeting molecule, an RGD peptide- and 4-(2-aminoethyl) morpholine-modified, doxorubicin (DOX)-loaded bovine serum albumin (BSA) nanomedicine, that can be controllably released by the high levels of autophagic lysosomes in tumour cells was developed. The size of the spherical BSA nanoparticles is approximately 60 nm. In vitro experiments indicated that the RGD peptide- and 4-(2-aminoethyl) morpholine-modified, DOX-loaded BSA nanomedicine has a better therapeutic effect than free DOX. In vivo experiments suggested that the BSA nanomedicine can successfully suppress the progression of PC9 xenograft tumours. This phenomenon may be attributable to the endocytosis of a relatively large amount of nanomedicine and the effective release of the loaded chemotherapeutic agent, as induced by high levels of autolysosomes. Collectively, the results of this study provide a smart approach for increasing therapeutic efficacy using a double-targeting molecule-modified BSA nanomedicine.
靶向修饰和智能响应的纳米药物可以使抗癌药物选择性地递送到肿瘤细胞或组织中，并进行可控释放，从而降低治疗的毒性和副作用。任何纳米药物的临床应用都需要良好的生物相容性。在本研究中，开发了一种双靶向分子，即 RGD 肽和 4-(2-氨基乙基)吗啉修饰的、载多柔比星（DOX）的牛血清白蛋白（BSA）纳米药物，它可以通过肿瘤细胞中高水平的自噬溶酶体进行可控释放。球形 BSA 纳米颗粒的大小约为 60nm。体外实验表明，RGD 肽和 4-(2-氨基乙基)吗啉修饰的、载 DOX 的 BSA 纳米药物比游离 DOX 具有更好的治疗效果。体内实验表明，BSA 纳米药物可以成功抑制 PC9 异种移植瘤的进展。这种现象可能归因于大量纳米药物的内吞作用和有效释放负载的化疗药物，这是由高水平的自溶酶体诱导的。总的来说，本研究的结果为使用双靶向分子修饰的 BSA 纳米药物提高治疗效果提供了一种智能方法。
