Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide

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.

Automated summary

Nanoparticles have been effective carriers for delivering anticancer drugs to the brain, with liposomal temozolomide being a preferred choice for treating brain tumors. However, the therapeutic benefit of liposomal TMZ is often suboptimal due to inefficient tumor penetration. Recent research has shown that the protein corona surrounding NPs after exposure to human plasma plays a crucial role in determining their anticancer efficacy by facilitating interactions with specific receptors of target cells. By coating liposomal TMZ with a protein corona made of human plasma proteins, researchers were able to increase drug penetration in a 3D brain cancer model and inhibit tumor growth. Fine-tuning the composition of the corona also showed varying effects on tumor growth, clarifying that certain protein corona fingerprints enable favored interactions with specific receptors of brain cancer cells. These findings suggest the potential of developing corona-coated liposomal drugs with enhanced tumor penetration and antitumor efficacy.