Biomimetic camouflaged nanoparticle-based folfirinox platform for optimizing clinical pancreatic cancer treatment

The most effective treatment of pancreatic cancer (PC) is known as mFOLFIRINOX scheme. However, this regimen has relatively severe toxic effects and are commonly restricted to patients with sound physique, which is poor in drug-selectivity, non-specific causing serious toxicity, greatly limits clinical application. Safer and more effective strategy seamlessly and synchronously is needed as advanced treatments for pancreatic cancer in future. In this report, we exploit a biomimetic nanoparticle-based platform for optimizing mFOLFIRINOX regimen. By coating pancreatic cancer cell membrane (PCCM) onto the surface of polymeric cores that loaded with mFOLFIRINOX, we prepare PCCM-cloaked nanoparticles, namely CNP@folfirinox, which inherit the antigenic exterior structure and associated functions of PC cells. The resulting CNP@folfirinox displays a core-shell nanostructure, which consisting of polymeric core and cancer cell membrane shell with suitable size and surface charge. Particularly, owing to inheriting the inherent membrane protein expressions profile, CNP@folfirinox exhibits prominent advantages in homologous homing to tumor tissue and deep penetration. It also shows lower side effects compared to extensive mFOLFIRINOX i.v. administration with no appreciable toxicity in other organs outside the tumor in vivo. Meanwhile, CNP@folfirinox is endowed with the "Don't eat me" privilege, hard for the immune system to recognize and less reticuloendothelial system uptake, with prolonged blood circulation, therefore improving delivery efficiency of drug after intravenous administration. Thus, this work reshapes a promising paradigm for more safe and more effective mFOLFIRINOX strategy for further clinical pancreatic cancer treatment.