title: Highly efficient nuclear delivery of anti-cancer drugs using a bio-functionalized reduced graphene oxide.
abstract: Targeted drug delivery has become important, attractive and challenging in biomedical science and applications. Anti-HER2 antibody-conjugated poly-l-lysine functionalized reduced graphene oxide (anti-HER2-rGO-PLL) nanocarriers were prepared to efficiently deliver doxorubicin targeting at the nucleus of HER2 over-expressing cancer cells. The polycationic PLL was first covalently grafted to graphene oxide (GO) nanosheets followed by reduction to obtain rGO-PLL with high drug loading and good colloidal stability. The anti-HER2 antibodies were subsequently conjugated to the amino groups of PLL to achieve excellent cell uptake capability. Cellular uptake of anti-HER2-rGO-PLL into MCF7/HER2 cells is significantly higher than that of rGO-PLL due to the specific targeting of anti-HER2 to HER2 overexpressing breast cancer cells. Additionally the anti-HER2-rGO-PLL enables a fast accumulation of DOX inside the nucleus, its subcellular site of action. In vitro cytotoxicity measurements clearly reveal a seven fold improvement in the anticancer efficacy for anti-HER2-rGO-PLL/DOX in comparison to rGO-PLL/DOX. The enhanced anticancer efficacy could be ascribed to the different intracellular DOX distributions resulted from the different internalization routes that are energy-dependent macropinocytosis and energy-independent direct penetration by anti-HER2-rGO-PLL and rGO-PLL, respectively. The results demonstrate that anti-HER2 conjugated rGO-PLL developed is a promising vehicle for efficient nuclear delivery of chemotherapeutic agents to HER2 over-expressing tumours.
authors.affiliation: Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, Chongqing 400715, China; Faculty of Materials and Energy, Southwest University, Chongqing 400715, China; Institute for Clean Energy & Advanced Materials, Southwest University, Chongqing 400715, China.
authors.forename: Xin Ting
authors.initials: XT
authors.lastname: Zheng
authors.affiliation: Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, Chongqing 400715, China; Faculty of Materials and Energy, Southwest University, Chongqing 400715, China; Institute for Clean Energy & Advanced Materials, Southwest University, Chongqing 400715, China.
authors.forename: Xiao Qing
authors.initials: XQ
authors.lastname: Ma
authors.affiliation: Institute of Material Science and Devices, Suzhou University of Science and Technology, Suzhou 215011, China; Chongqing Key Laboratory for Advanced Materials and Technologies of Clean Energies, Chongqing 400715, China; Faculty of Materials and Energy, Southwest University, Chongqing 400715, China; Institute for Clean Energy & Advanced Materials, Southwest University, Chongqing 400715, China. Electronic address: ecmli@swu.edu.cn.
authors.forename: Chang Ming
authors.initials: CM
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D061986:MCF-7 Cells; D010084:Oxidation-Reduction; D010087:Oxides / Q000737:chemistry*; D010316:Particle Size; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010087:Oxides; D006108:Graphite
keywords: Anti-cancer drugs; Breast cancer; Drug delivery; Endocytosis; Poly-l-lysine; Reduced graphene oxide