Boosting the Theranostic Effect of Liposomal Probes toward Prominin-1 through Optimized Dual-Site Targeting.

Ligand-targeting specific liposomal probes are increasingly used as imaging and delivery vehicles for in vivo diagnosis. Thereinto, the ligand variety and density profoundly affect the binding behaviors toward the target. The synergetic effect of different ligands could be achieved only when the optimized molecular-recognition configuration occurred. In this study, we construct a dual-peptides-targeting liposomal probe named BTLS that could synergistically bind two different sites of prominin-1, a cancer stem cell marker. At the distance of 11 Å between the two new peptides, ligands could insert into the hollow pocket of prominin-1 and BTLS could achieve the appropriate spatial structure, showing the strong binding affinity in both cellular and in vivo levels. It is indicated that the design of density-optimized peptide-targeted liposomes could be promising to maximize the multifunctional targeting effects on the cancer theranostics.

Synergetic estrogen receptor-targeting liposome nanocarriers with anti-phagocytic properties for enhanced tumor theranostics.

Multifunctional nanocarriers have been widely applied due to their enhanced effect on tumor therapeutics. Nevertheless, owing to the natural immune clearance mechanisms in living bodies, nanocarriers tend to be eliminated during blood circulation, thereby impeding their effective arrival at the tumor sites. Herein, we constructed a synergetic targeted liposome nanocarrier system named SELS functionalized with both a tumor identification ligand (anti-ER (Estrogen Receptor) antibody) and an immune targeting ligand (Self-Peptide (SP)). The anti-ER antibody could recognize and bind ER-positive breast cancer tissues in a specific way. SP could activate the CD47-SIRPα immune response, which reduced phagocytosis of the nanoparticles by macrophages. Both the enhanced targeting ability and anti-phagocytosis behavior could improve the tumor uptake of the nanocarriers and prevent their immune clearance in living systems. Therefore, drug-loaded SELS enabled improved tumor imaging and therapeutic performance in living systems.

Quantitative proteomic analysis to the first commercialized liposomal paclitaxel nano-platform Lipusu revealed the molecular mechanism of the enhanced anti-tumor effect.

The first nano-platform commercialized as a drug delivery system was a liposomal formulation. The application of liposome technology resolved the issues of paclitaxel (PTX) insolubility and eliminated the use of solvents causing toxic side-effects, which enabled to apply higher drug doses leading to an enhanced drug efficacy. The growth-inhibitory activity of liposome-encapsulated PTX was retained in vitro against a variety of tumor cell. To investigate the drug efficacy in the system biological level, quantitative proteomic analysis was employed to study the molecular mechanism of the anti-tumor effect of Lipusu® (lip) compared with PTX on lung cancer cell A549. The functions of the differential expressed proteins were correlated to the negative effect to cell proliferation due to regulation of hippo pathway and prolonged cell cycle, as well as inhibitory cell exocytosis, which would cause the aggregation of free PTX. This investigation focused on the direct biological effect of lip to cancer cells. It was different from pharmaceutical issues about drug exposure, delivery and distribution which were widely investigated in other traditional studies. It was the first study about the drug effect of lip from the global molecular biological aspect.