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.

Theranostic Probes for Targeting Tumor Microenvironment: An Overview

“…Zheng et al conducted a study to explore the efficiency of graphene NPs in both drug delivery as well as imaging probe. They inferred that these NPs have greater surface area which increases the amount of drug loaded on a single NP [48]. These nanocarriers efficiently deliver the doxorubicin to the cancer nucleus in order to overexpress the HPR2 antibodies which in turn would make high internalization with the cancer nucleus.…”

Theranostic Probes for Targeting Tumor Microenvironment: An Overview

“…Zheng et al conducted a study to explore the efficiency of graphene NPs in both drug delivery as well as imaging probe. They inferred that these NPs have greater surface area which increases the amount of drug that can be loaded on a single NP [129]. …”

Graphene‐Oxide‐Decorated Microporous Polyetheretherketone with Superior Antibacterial Capability and In Vitro Osteogenesis for Orthopedic Implant

“…Furthermore, GO nanosheets display apparent antimicrobial capabilities for Gram‐negative and Gram‐positive bacteria . Hence, GO has been widely applied in various biotechnologies and biomedical applications such as biosensor, cellular imaging, nanoprobe, drug delivery, and tissue engineering . Nevertheless, the nanotoxic danger has raised a live issue discussion.…”