Multifunctional chitosan magnetic-graphene (CMG) nanoparticles: a theranostic platform for tumor-targeted co-delivery of drugs, genes and MRI contrast agents

Abstract

Combining chemotherapy with gene therapy has been one of the most promising strategies for the treatment of cancer. Noninvasive MRI with superparamagnetic iron oxide (SPIO) as a contrast agent is one of the most effective techniques for evaluating antitumor therapy. However, constructing a single system that can deliver efficiently gene, drug and SPIO to the cancer site remains a challenge. Herein, we report a chitosan functionalized magnetic graphene (CMG) nanoparticle platform for simultaneous gene/drug and SPIO delivery to tumor. The phantom and ex vivo MRI suggest CMG as a strong T₂ contrast-enhancing agent. CMGs are biocompatible as evaluated by the WST assay and predominantly accumulate in tumors as shown by biodistribution studies and MRI. The anticancer drug doxorubicin (DOX) loaded CMGs (DOX–CMGs) release DOX faster at pH 5.1 than at pH 7.4, and are more effective (IC₅₀ = 2 μM) in killing A549 lung cancer cells than free DOX (IC₅₀ = 4 μM). CMGs efficiently deliver plasmid DNA into A549 lung cancer cells and C42b prostate cancer cells. In addition, i.v. administration of plasmid DNA encoding green fluorescent protein (GFP) encapsulated within DOX–CMGs into tumor-bearing mice has shown both GFP expression and DOX accumulation at the tumor site at 24 and 48 h after administration. These results indicate that CMGs provide a robust and safe theranostic platform, which integrates targeted delivery of both gene medicine and chemotherapeutic drug(s), and enhanced MR imaging of tumors. The integrated chemo- and gene-therapeutic and diagnostic design of CMG nanoparticles shows promise for simultaneous targeted imaging, drug delivery and real-time monitoring of therapeutic effects for cancer.