Surface functionalisations substantially influence the performance of drug delivery vehicles by improving their biocompatibility, selectivity and circulation in bloodstream. Herein, we present the study of in vitro and in vivo behaviour of a highly potent cytostatic alkaloid ellipticine (Elli) encapsulated in internal cavity of ferritin (FRT)-based nanocarrier (hereinafter referred to as FRTElli). In addition, FRTElli surface was functionalised with three different molecular coatings: two types of protective PAS peptides (10- or 20-residues lengths) with sequences comprising amino acids proline (P), alanine (A) and serine (S) (to form PAS-10-FRTElli or PAS-20-FRTElli, respectively), or polyethylene glycol (PEG-FRTElli). All three surface modifications of FRT disposed sufficient encapsulation efficiency of Elli with no premature cumulative release of cargo. Noteworthy, all tested surface modifications displayed beneficial effects on the in vitro biocompatibility. PAS-10-FRTElli exhibited markedly reduced uptake by macrophages compared to PAS-20-FRTElli, PEG-FRTElli or unmodified FRTElli. The exceptional properties of PAS-10-FRTElli were validated by an array of in vitro analyses including formation of protein corona, uptake efficiency or screenings of selectivity of cytotoxicity. In murine preclinical model bearing triple-negative breast cancer (MDA-MB-231) xenograft, compared to free Elli or FRTElli, PAS-10-FRTElli displayed enhanced accumulation of Elli within tumour tissue, while hampering the uptake of Elli into off-target tissues. Noteworthy, PAS-10-FRTElli led to decreased in vivo complement (C3) activation and protein corona formation. Taken together, presented in vivo results indicate that PAS-10-FRTElli represents a promising stealth platform for translation into clinical settings.

表面功能化通过改善其生物相容性，选择性和血液循环来极大地影响药物递送载体的性能。在这里，我们提出体外和体内的研究封装在基于铁蛋白（FRT）的纳米载体（以下简称FRTE1li）内腔中的高效细胞生长抑制生物碱玫瑰树碱（Elli）的行为。此外，FRTEIli表面还用三种不同的分子涂层进行功能化：两种类型的保护性PAS肽（长度为10或20个残基），其序列包含氨基酸脯氨酸（P），丙氨酸（A）和丝氨酸（S）（形成PAS-10-FRTElli或PAS-20-FRTElli）或聚乙二醇（PEG-FRTElli）。FRT的所有三个表面修饰都具有足够的Elli封装效率，并且不会过早地累积货物。值得注意的是，所有测试过的表面改性都对体外产生了有益的影响。生物相容性。与PAS-20-FRTElli，PEG-FRTElli或未修饰的FRTElli相比，PAS-10-FRTElli表现出的巨噬细胞摄取显着降低。通过一系列体外分析，包括蛋白电晕的形成，吸收效率或细胞毒性选择性筛选，验证了PAS-10-FRTElli的优异性能。在携带三阴性乳腺癌（MDA-MB-231）异种移植物的小鼠临床前模型中，与游离Elli或FRTElli相比，PAS-10-FRTElli显示出Elli在肿瘤组织中的积累增强，同时阻碍了Elli对脱靶的摄取。组织。值得注意的是，PAS-10-FRTElli导致体内补体（C3）活化和蛋白质电晕形成减少。两者合计，呈现在体内 结果表明，PAS-10-FRTElli代表了一个有前途的隐形平台，可用于翻译为临床环境。