Site-specific delivery of a natural chemotherapeutic agent to human lung cancer cells using biotinylated 2D rGO nanocarriers

Highlights

• We developed non-immunogenic, biocompatible biotin-adorned PBA-coated GA-loaded rGONC (BPBA@GA-rGONC).

• Method-2 was able to load high amount of GA and also safe from enzymatic degradation and phagocytosis process shielded by PBA.

• GA (green route) reduced rGONC was non-toxic and demonstrated superior dispersity as well as stability in an aqueous medium.

• BPBA@GA-rGONC was responsible to direct high concentration of GA on cancer cells.

• GA was released in high amount in endosomes-pH compared to blood-pH.

Abstract

Chemotherapy has remained one of the most commonly employed treatment modalities for cancer. Despite the clinical availability of a large number of chemotherapeutic agents, the uncontrolled systemic distribution and the associated harmful side effects of chemotherapeutic agents pose major challenges demanding concerted efforts to enhance their cancer targetability. The layered structure of two-dimensional (2D) materials offers new opportunities by increasing the drug pay-load influencing the drug-release kinetics in a cancer micro-environment and facilitating targetability through the large accessible surface area. To investigate such potential benefits of 2D materials, we have developed a biocompatible targeted 2D drug delivery system using graphene oxide (GO) as a model nanocarrier (NC) that could hold a high concentration of gallic acid (GA), a natural chemotherapeutic agent found in green tea. Interestingly, the antioxidant nature of GA also reduced GO to a high-quality few-layered thin reduced-graphene oxide (rGO) during drug loading while forming rGO nanocarrier (rGONC). The biotinylated rGONC further improved their targetability to A549 human lung carcinoma cells and they enhanced cellular internalization efficiency. From these targeted 2D NCs, the drug could release only slowly at the physiological pH but liberated rapidly at lower pH encountered by the tumor microenvironment resulting in significant toxicity toward the lung carcinoma cells. As such, this work opens up new possibilities for employing 2D materials for targeted chemotherapeutic applications.