Biomimetic nanosystems for pancreatic cancer therapy: A review

Pancreatic cancer (PC) is a highly lethal and aggressive malignancy, currently one of the leading causes of cancer-related deaths worldwide, in both women and men. PC is highly resistant to standard chemotherapy (CT) because its immunosuppressive and hypoxic tumor microenvironment and a dense desmoplastic stroma compartment extensively limit drug accessibility and perfusion. Although CT is one of the main therapeutic strategies for PC management contributing to tumor eradication through a cytotoxic effect, CT is associated with a poor pharmacokinetic profile and provokes deleterious systemic toxicity. This low efficacy-poor safety scenario urgently calls for innovative and highly specific therapeutic strategies to counteract this urgent clinical challenge. Nanotechnology-based precision materials for cancer may help improve drug stability and minimize the systemic cytotoxic effects by increasing drug tumor accumulation and also enabling controlled release, but several drawbacks still persist, such as the poor targeting efficiency. In the last few years increased attention has been paid to bioinspired nanosystems that can mimic either partially or totally biological systems, including lipid layers as suitable stealth coatings resembling the composition of cell membranes, lipoprotein- and blood protein-based nanosystems, and cell membrane-derived systems, such as extracellular vesicles, cell membrane nanovesicles and cell membrane-coated nanosystems, which display intrinsic cancer-targeting abilities, enhanced biocompatibility, decreased immunogenicity, and prolonged blood circulation profile. This review covers the recent breakthroughs on advanced biomimetic PC-targeted nanosystems, focusing on their design, properties and applications as innovative, multifunctional and versatile tools paving the way to improved PC diagnosis and treatment.