RESUMO
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.
Assuntos
Membrana Celular , Doxorrubicina , Sistemas de Liberação de Medicamentos , Lipossomos , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Lipossomos/química , Animais , Humanos , Camundongos , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/química , Oligopeptídeos/química , Camundongos Endogâmicos BALB C , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem , Linhagem Celular Tumoral , Camundongos Nus , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Distribuição Tecidual , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Based on the immune escape and homologous adhesion ability of cancer cells, a drug delivery system (DDS) could overcome the dilemma of immune clearance and non-specific binding by coating the cancer cell membrane (CCM). In this study, a biomimetic DDS based on CCM and poly lactic acid-glycolic acid (PLGA) nanoparticles was successfully constructed for tumor active and homologous targeting therapy. The doped CCM on the surface of the nanoparticle enabled the DDS to achieve immune escape and had an affinity for tumor tissues. The cellular uptake and in vivo distribution tests showed a superior cellular affinity of CCM coated PLGA nanoparticles (CCMNPs) than that of PLGA nanoparticles (PLGANPs). All of those results proved that CCMNPs endowed with drug-loaded nanoparticles had the abilities of immune escape and homologous targeting through the biological functional proteins retained on the coated CCM. In addition, the tumor inhibition rate of CCMNPs in tumor-bearing nude mice was 1.3 and 2.0-fold compared to PLGANPs and PTX injection, which showed the capacity to efficiently and accurately deliver drugs to cancer sites improved the therapeutic effect of tumor and achieved accurately targeted therapy.