Self-assembled chitosan/rose bengal derivative nanoparticles for targeted sonodynamic therapy: preparation and tumor accumulation

Sonodynamic therapy (SDT) is expected to be a promising novel therapeutic strategy for non-invasive cancer treatment. Rose bengal (RB), which serves as a typical photosensitizer, can also be activated by ultrasound and has high potential to be a sonosensitizer for SDT. However, the fast elimination rate and poor tumor accumulation of RB greatly limit its in vivo applications. The aim of this work is to synthesize a rose bengal derivative (rose bengal u-carboxyheptyl ester, RBD), prepare chitosan (CS)/RBD complex nanoparticles (RBDCNs), and investigate the cellular uptake and tumor accumulation of RBDCNs in cancer cell lines and a transplanted colon cancer mouse model. CS and RBD could form complex nanoparticles with a particle size of 150-200 nm and positive surface charges (>+40 mV) at a mass ratio 1. The addition of CS conferred a remarkable decrease in the fluorescent intensity of RBD, suggesting the inclusion of dye within the complex nanoparticles. RBDCNs showed good stability in the medium containing salt ions with dye leakage of less than 20%, while the high concentration of serum could affect the interaction between CS and RBD, resulting in about 75% dye leakage under a 10% FBS condition. RBDCNs could achieve more efficient cellular uptake in HT29 and HepG2 cells than RB, RBD, or CS/RB complex nanoparticles (RBCNs). The high accumulation of RBDCNs in tumors was also observed when RBDCNs were intravenously injected into CT-26 colon cancer transplanted Balb/c mice. These results suggested that RBDCNs could be efficient and promising tumor targeting delivery systems.