Theranostics 2018; 8(2):518-532. doi:10.7150/thno.21194
A Transferrin-Conjugated Hollow Nanoplatform for Redox-Controlled and Targeted Chemotherapy of Tumor with Reduced Inflammatory Reactions
1. School of Life Science, Chongqing University, Chongqing 400044, P. R. China;
2. Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371;
3. Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing University, Chongqing 400044, P. R. China;
4. Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;
5. School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798.
* These authors contributed equally to this work.
Purpose: In this study, we report the design, development and evaluation of a hollow drug delivery nanoplatform for cancer therapy in vitro and in vivo. This composite nanosystem was prepared by modifying hollow mesoporous silica nanoparticles (HMSNs) with transferrin (Tf) targeting moieties via redox-liable linkage, and was capable of delivering therapeutic cargos (doxorubicin) specifically to the tumor site and subsequently releasing them in an on-demand manner. Moreover, the Tf corona could simultaneously reduce the inflammatory response after intravenous administration in vivo.
Methods: Nanostructural morphology of the drug delivery system was observed by scanning electron microscope and transmission electron microscope. The preparation process was monitored primarily using Fourier-transform infrared spectroscopy, dynamic light scattering, nitrogen adsorption/desorption isotherm, and thermogravimetric analysis. The release profile in solution was monitored by fluorescence spectroscopy. In vitro drug delivery efficacy was evaluated on MDA-MB-231 breast cancer cell line using confocal laser scanning microscopy, MTT assay and flow cytometry. In vitro inflammatory response was evaluated on RAW264.7 macrophage cells. In vivo therapeutic experiments were carried out using in situ mouse breast cancer models.
Results: The experimental results evidently demonstrate that the developed nanocarrier could effectively deliver anticancer drugs to the tumor site in a targeted manner and release them in response to the elevated glutathione level inside tumor cells, resulting in improved anticancer efficacy both in vitro and in vivo. Moreover, the Tf conjugation significantly ameliorated the inflammatory reaction triggered by the administration of the nanocarrier.
Conclusions: This manuscript demonstrated that the Tf-conjugated HMSNs could enhance the delivery efficiency of anticancer drugs, while simultaneously alleviating the adverse side effects. The current study presents a promising integrated delivery system toward effective and safe cancer treatment.
Keywords: attenuation of inflammation, hollow mesoporous silica nanoparticles, redox-responsive release, targeted chemotherapy, transferrin conjugation.
Zhou J, Li M, Lim WQ, Luo Z, Phua SZF, Huo R, Li L, Li K, Dai L, Liu J, Cai K, Zhao Y. A Transferrin-Conjugated Hollow Nanoplatform for Redox-Controlled and Targeted Chemotherapy of Tumor with Reduced Inflammatory Reactions. Theranostics 2018; 8(2):518-532. doi:10.7150/thno.21194. Available from http://www.thno.org/v08p0518.htm