Dual targetable drug delivery system based on cell membrane camouflaged liposome for enhanced tumor targeting and improved anti-tumor efficiency

Abstract

Receptor and ligand binding mediated targeted drug delivery systems (DDS) sometimes fail to target to tumor sites, and cancer cell membrane (CCM) coating can overcome the dilemma of immune clearance and nonspecific binding of DDS in vivo. In order to enhance the targeting ability and improve the anti-tumor effect, a dual targeting DDS was established based on U87MG CCM mediated homologous targeting and cyclic peptide RGD mediated active targeting. The DDS was prepared by coating RGD doped CCM onto doxorubicin (DOX) loaded liposomes. The homologous and active dual targeting ability endowed the DDS (RGD-CCM-LP-DOX) exhibited superior cancer cell affinity, improved tissue distribution and enhanced anti-tumor effects. In vivo pharmacodynamic studies revealed that RGD-CCM-LP-DOX exhibited superior therapeutic effect compared with homologous targeting CCM-LP-DOX and non-targetable LP-DOX injection. H&E staining, Ki 67 staining and TUNEL staining confirmed that RGD-CCM-LP-DOX not only increased anti-tumor efficacy, but also reduced tissue toxicity by changing the distribution in vivo. The experimental results showed that the RGD doped CCM camouflaged liposome DDS is a better choice for chemotherapeutics delivery.