Perini Giordano, Giulimondi Francesca, Palmieri Valentina, Augello Alberto, Digiacomo Luca, Quagliarini Erica, Pozzi Daniela, Papi Massimiliano, Caracciolo Giulio
Dipartimento di Neuroscienze, Università Cattolica del Sacro Cuore, Largo Francesco Vito 1, 00168 Rome, Italy.
Fondazione Policlinico Universitario A. Gemelli IRCSS, 00168 Rome, Italy.
Pharmaceutics. 2021 Mar 12;13(3):378. doi: 10.3390/pharmaceutics13030378.
Nanoparticles (NPs) have emerged as an effective means to deliver anticancer drugs into the brain. Among various forms of NPs, liposomal temozolomide (TMZ) is the drug-of-choice for the treatment and management of brain tumours, but its therapeutic benefit is suboptimal. Although many possible reasons may account for the compromised therapeutic efficacy, the inefficient tumour penetration of liposomal TMZ can be a vital obstacle. Recently, the protein corona, i.e., the layer of plasma proteins that surround NPs after exposure to human plasma, has emerged as an endogenous trigger that mostly controls their anticancer efficacy. Exposition of particular biomolecules from the corona referred to as protein corona fingerprints (PCFs) may facilitate interactions with specific receptors of target cells, thus, promoting efficient internalization. In this work, we have synthesized a set of four TMZ-encapsulating nanomedicines made of four cationic liposome (CL) formulations with systematic changes in lipid composition and physical-chemical properties. We have demonstrated that precoating liposomal TMZ with a protein corona made of human plasma proteins can increase drug penetration in a 3D brain cancer model derived from U87 human glioblastoma multiforme cell line leading to marked inhibition of tumour growth. On the other side, by fine-tuning corona composition we have also provided experimental evidence of a non-unique effect of the corona on the tumour growth for all the complexes investigated, thus, clarifying that certain PCFs (i.e., APO-B and APO-E) enable favoured interactions with specific receptors of brain cancer cells. Reported results open new perspectives into the development of corona-coated liposomal drugs with enhanced tumour penetration and antitumour efficacy.
纳米颗粒（NPs）已成为将抗癌药物输送到大脑的有效手段。在各种形式的纳米颗粒中，脂质体替莫唑胺（TMZ）是治疗和管理脑肿瘤的首选药物，但其治疗效果并不理想。尽管许多可能的原因可以解释治疗效果受损，但脂质体替莫唑胺在肿瘤中的渗透效率低下可能是一个关键障碍。最近，蛋白质冠层，即纳米颗粒在暴露于人体血浆后周围形成的一层血浆蛋白，已成为一种主要控制其抗癌功效的内源性触发因素。来自蛋白质冠层的特定生物分子（称为蛋白质冠层指纹图谱，PCFs）的暴露可能促进与靶细胞特定受体的相互作用，从而促进有效的内化。在这项工作中，我们合成了一组由四种阳离子脂质体（CL）制剂制成的包裹替莫唑胺的纳米药物，这些制剂在脂质组成和物理化学性质上有系统的变化。我们已经证明，用人血浆蛋白制成的蛋白质冠层预包被脂质体替莫唑胺，可以增加其在源自U87人多形性胶质母细胞瘤细胞系的三维脑癌模型中的药物渗透，从而显著抑制肿瘤生长。另一方面，通过微调冠层组成，我们还为所有研究的复合物提供了蛋白质冠层对肿瘤生长具有非唯一作用的实验证据，从而阐明某些PCFs（即载脂蛋白B和载脂蛋白E）能够促进与脑癌细胞特定受体的相互作用。报道的结果为开发具有增强肿瘤渗透和抗肿瘤功效的冠层包被脂质体药物开辟了新的前景。
