Multi-functionalized single-walled carbon nanotubes as delivery carriers: promote the targeting uptake and antitumor efficacy of doxorubicin

Abstract

As one of carbon-based nanomaterials, single-walled carbon nanotubes (SWCNTs) are widely regarded as potentially potent drug delivery carriers on account of their prominent properties. Nevertheless, their biomedical application, particularly in the drug delivery field has been seriously restricted by some inherent defects. In this study, SWCNTs materials were functionalized by covalent and non-covalent approaches, respectively. In short, the pristine SWCNTs were first purified with strong oxidizing acids (H₂SO₄/HNO₃), and the resulting carboxylated ones (CNTs) were attached sequentially by different modification agents, including polyethylene glycol (PEG), polyethyleneimine (PEI), folic acid (FA) and chitosan (CS). Various nanocarriers were then systematically characterized and comparatively evaluated. The results illustrated that all CNTs samples could act as drug delivery carriers since they had high drug loading efficiency, good biocompatibility and responsive drug release. In comparison with other CNTs, multi-functionalized ones (CNTs-PPFC) exhibited more excellent performance, such as rapid drug release at low pH condition, higher cell internalization efficiency, and enhanced antitumor activity toward MCF-7 cells. These advantages should be attributed to their better dispersion state and comparably higher affinity with tumor cells, which favor the more efficient selective cellular uptake and subsequent drug accumulation. Moreover, further pharmacological mechanism analysis also revealed that CNTs-PPFC/DOX could induce the apoptosis of MCF-7 cells most effectively, by triggering ROS overproduction and affecting cell cycle distribution. In conclusion, the multi-functionalized CNTs-PPFC can be utilized as promising nanocarriers, and the findings will contribute to the rational design of novel delivery vehicles for anticancer drugs.