A Transferrin-Conjugated Hollow Nanoplatform for Redox-Controlled and Targeted Chemotherapy of Tumor with Reduced Inflammatory Reactions
Authors: Liangliang Dai
Jun Zhou
Junjie Liu
Zhong Luo
Wei Qi Lim
Yanli Zhao
Soo Zeng Fiona Phua
Menghuan Li
Kaiyong Cai
Runlan Huo
Liqi Li
Ke Li
Journal: Theranostics (2018)
Discipline: CLINICAL MEDICINE
Keywords: attenuation of inflammation; hollow mesoporous silica nanoparticles; redox-responsive release; targeted chemotherapy; transferrin conjugation..
Affiliations: School of Life Science, Chongqing University, Chongqing 400044, P. R. China., Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371., Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China., Key Laboratory of Biorheological Science and Technology, Ministry of Education, Chongqing University, Chongqing 400044, P. R. China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 The images in Figure 3e1 and 3f appear to show overlapping fields of view, but seem to be described as being treated differently. ***  , 
 Two lung images in Figure 9 appear to overlap, but seem to be described differently. ***  , 
 #1 Thank you for bringing this issue to our attention. We have thoroughly checked the original data and found that the fluorescent imaging results regarding the uptake of HMSNs-S-S-Tf@FITC within MDA-MB-231 cell after incubation of 12 h (Figure 3f) and HMSNs@FITC at 24 h were erroneously duplicated when organizing the panels. The corrected version of Figure 3 is attached below.  #2 Thank you for bringing this issue to our attention. We have checked our work and found that inappropriate images were used for morphological analysis of major mouse organs after H E staining in Figure 9 due to our careless mistakes in panel numbering during figure assembly. The corrected image is shown here below:  The authors confirm that the corrections to these two figures do not affect the original conclusions and sincerely apologize for any inconvenience or misunderstanding that the errors may have caused. The authors have also contacted the journal and an erratum is underway. ,