Transferrin-modified nanostructured lipid carriers as multifunctional nanomedicine for codelivery of DNA and doxorubicin

Yiqun Han,^1,† Ying Zhang,^2,† Danni Li,³ Yuanyuan Chen,¹ Jiping Sun,¹ Fansheng Kong<sup>4

1</sup>Department of Respiratory Medicine, General Hospital of Ji’nan Command, PLA, ²Center of Interventional Therapy, Ji’nan Infectious Disease Hospital, ³Department of Internal Neurology, Ji’nan Central Hospital Affiliated to Shandong University, ⁴Department of Hematology, General Hospital of Ji’nan Command, PLA, Ji’nan, People’s Republic of China

^†These two authors contributed equally to this work

Background: Nanostructured lipid carriers (NLC), composed of solid and liquid lipids, and surfactants are potentially good colloidal drug carriers. The aim of this study was to develop surface-modified NLC as multifunctional nanomedicine for codelivery of enhanced green fluorescence protein plasmid (pEGFP) and doxorubicin (DOX).
Methods: Two different nanocarriers: pEGFP- and DOX-loaded NLC, and solid lipid nanoparticles (SLN) were prepared. Transferrin-containing ligands were used for the surface coating of the vectors. Their average size, zeta potential, and drug encapsulation capacity were evaluated. In vitro transfection efficiency of the modified vectors was evaluated in human alveolar adenocarcinoma cell line (A549 cells), and in vivo transfection efficiency of the modified vectors was evaluated in a mouse bearing A549 cells model.
Results: Transferrin-modified DOX and pEGFP coencapsulated NLC (T-NLC) has a particle size of 198 nm and a +19 mV surface charge. The in vitro cell viabilities of the T-NLC formulations were over 80% compared with the control. T-NLC displayed remarkably greater gene transfection efficiency and enhanced antitumor activity than DOX- and pEGFP-coencapsulated SLN in vivo.
Conclusion: The results demonstrate that T-NLC noticeably enhanced antitumor activity through the combination of gene therapy with chemotherapy. Also coating of active transferrin improved the lung cancer cell-targeting of the carriers. In summary, the novel gene and drug delivery system offers a promising strategy for the treatment of lung cancer.

Keywords: multifunctional delivery system, active targeting, transferrin modification, solid lipid nanoparticles