Fabrication of an EGF modified nanodiamonds-based anti-cancer drug targeted delivery system and drug carrier uptake visualization by 3D Raman microscopy

Abstract

A nanodiamonds-based anti-cancer drug targeted delivery system, Epidermal Growth Factor (EGF)–nanodiamonds (NDs)–cisplatin (ENC) bioconjugate was developed. Due to the effect of the specific biorecognition process of EGF (a kind of targeting molecule), human liver hepatocellular carcinoma (HepG2) cells could be selectively killed by the ENC system, even in a lower concentration of the cisplatin (a kind of anti-cancer drug) comparing to the traditional drug therapy. The cytotoxicity of ENC could be blocked by EGFR antibody in cancer cells, revealing the specificity of its targeting ability. Because the morphological change of HepG2 cells treated by ENC was observed, from epithelial to mesenchymal-like shape, the related mechanism was evaluated. The results showed that E-cadherin expression declined after ENC treatment, while vimentin expression did not change. The decrease of E-cadherin expression means the loss of cell–cell adhesion. Loose cells provided more specific surface area for drug absorption. Based on these advantages, ENC delivery system would be a promising targeting drug delivery system. Moreover, we located the spatial distribution of ENC system in cells by using the NDs existing in ENC as Raman probe through 3-dimensional (3D) confocal Raman imaging, i.e., we were able to visualize the process of uptake of ENC into living cancer cells, which is helpful to observe the specific biorecognition process between EGF and its receptor (EGFR) in a physiology condition and the cellular uptake of ENC drug delivery system. The present study demonstrates that drug-loaded NDs have a potential as novel intravascular probes for both diagnostic (e.g., imaging) and therapeutic purposes (e.g., targeted drug delivery).