Improving Bioavailability of Hydrophobic Prodrugs through Supramolecular Nanocarriers Based on Recombinant Proteins for Osteosarcoma Treatment

Abstract

Supramolecular nanodrug assembly driven by supramolecular chemistry is becoming a powerful strategy for medication. The potential of engineered proteins as building blocks for nanoformulations is rarely investigated. Here, we developed a new generation of recombinant proteinbased nanodrug carriers, which is very efficient for loading and delivering the hydrophobic prodrug aldoxorubicin. Significantly enhanced anti-tumor effects in osteosarcoma (OS) models were observed. The half-life of the nanodrug reached almost two days and the corresponding bioavailability increased by 17-fold. This is significantly superior to other drug counterparts, empowering long-acting OS treatment scenarios. Importantly, off-target side effects of the prodrug, including cardiotoxicity and lung-metastasis, were greatly mitigated with our medication. Thus, our assembly strategy enables the customized design of advanced nanodelivery systems employing broader biomaterial building blocks for cancer therapy.

Bioengineered Protein‐based Adhesives for Biomedical Applications

“…As a typically disordered proteins, elastin-like polypeptides (ELPs) have been widely investigated over the decades. [37][38][39][40][41] It is known that ELPs consist of a repeat pentapeptide unit (VPGXG), where X can be replaced by other amino acids (Figure 2). These repeat units are derived from the alternating hydrophobic or hydrophilic domains of tropoelastin.…”

Enzyme-instructed morphology transformation of mitochondria-targeting peptide for the selective eradication of osteosarcoma

“…[8][9][10][11] Accordingly, mitochondria targeting supramolecular therapy can be envisaged as a promising method for the treatment of osteosarcoma. 12,13 In general, mitochondrion-targeting supramolecular therapy uses a nontoxic self-assembling small molecule (e.g., an amphiphilic peptide or the monomer of a polymer) to target the tumor. The self-assembly of this agent within the mitochondria leads to cell death via mitochondrial disruption and the consequent release of apoptotic bodies.…”