Theranostics 2020; 10(25):11607-11621. doi:10.7150/thno.46228 This issue Cite

Research Paper

Hemoglobin-mediated biomimetic synthesis of paramagnetic O2-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor

Xiudong Shi1,2#, Weitao Yang3#, Qiong Ma1, Yang Lu1, Yan Xu3, Kexin Bian3, Fengjun Liu1,4, Chunzi Shi1, Han Wang2✉, Yuxin Shi1,4✉, Bingbo Zhang3✉

1. Department of Radiology, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
2. Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
3. The Institute for Translational Nanomedicine, Shanghai East Hospital; The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai 200092, China.
4. Translational Medicine Center, Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
#These authors contributed equally to this study.

Citation:
Shi X, Yang W, Ma Q, Lu Y, Xu Y, Bian K, Liu F, Shi C, Wang H, Shi Y, Zhang B. Hemoglobin-mediated biomimetic synthesis of paramagnetic O2-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor. Theranostics 2020; 10(25):11607-11621. doi:10.7150/thno.46228. https://www.thno.org/v10p11607.htm
Other styles

File import instruction

Abstract

Graphic abstract

The hypoxic microenvironment in solid tumors severely limits the efficacy of photodynamic therapy (PDT). Therefore, the development of nanocarriers co-loaded with photosensitizers and oxygen, together with imaging guidance ability, is of great significance in cancer therapy. However, previously reported synthetic methods for these multi-functional probes are complicated, and the raw materials used are toxic.

Methods: Herein, the human endogenous protein, hemoglobin (Hb), was used for the simultaneous biomimetic synthesis of Gd-based nanostructures and co-loading of Chlorine e6 (Ce6) and oxygen for alleviating the hypoxic environment of tumors and accomplishing magnetic resonance imaging (MRI)-guided enhanced PDT. The Gd@HbCe6-PEG nanoprobes were synthesized via a green and protein biomimetic approach. The physicochemical properties, including relaxivity, oxygen-carrying/release capability, and PDT efficacy of Gd@HbCe6-PEG, were measured in vitro and in vivo on tumor-bearing mice after intravenous injection. Morphologic and functional MRI were carried out to evaluate the efficacy of PDT.

Results: The results demonstrated the successful synthesis of compact Gd@HbCe6-PEG nanostructures with desired multi-functionalities. Following treatment with the nanoparticles, the embedded MR moiety was effective in lighting tumor lesions and guiding therapy. The oxygen-carrying capability of Hb after biomimetic synthesis was confirmed by spectroscopic analysis and oxygen detector in vitro. Further, tumor oxygenation for alleviating tumor hypoxia in vivo after intravenous injection of Gd@HbCe6-PEG was verified by photoacoustic imaging and immunofluorescence staining. The potent treatment efficacy of PDT on early-stage was observed by the morphologic and functional MR imaging. Importantly, rapid renal clearance of the particles was observed after treatment.

Conclusion: In this study, by using a human endogenous protein, we demonstrated the biomimetic synthesis of multi-functional nanoprobes for simultaneous tumor oxygenation and imaging-guided enhanced PDT. The therapeutic efficacy could be quantitatively confirmed at 6 h post PDT with diffusion-weighted imaging (DWI).

Keywords: biomimetic synthesis, MR imaging, tumor hypoxia, photodynamic therapy, endogenous protein


Citation styles

APA
Shi, X., Yang, W., Ma, Q., Lu, Y., Xu, Y., Bian, K., Liu, F., Shi, C., Wang, H., Shi, Y., Zhang, B. (2020). Hemoglobin-mediated biomimetic synthesis of paramagnetic O2-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor. Theranostics, 10(25), 11607-11621. https://doi.org/10.7150/thno.46228.

ACS
Shi, X.; Yang, W.; Ma, Q.; Lu, Y.; Xu, Y.; Bian, K.; Liu, F.; Shi, C.; Wang, H.; Shi, Y.; Zhang, B. Hemoglobin-mediated biomimetic synthesis of paramagnetic O2-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor. Theranostics 2020, 10 (25), 11607-11621. DOI: 10.7150/thno.46228.

NLM
Shi X, Yang W, Ma Q, Lu Y, Xu Y, Bian K, Liu F, Shi C, Wang H, Shi Y, Zhang B. Hemoglobin-mediated biomimetic synthesis of paramagnetic O2-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor. Theranostics 2020; 10(25):11607-11621. doi:10.7150/thno.46228. https://www.thno.org/v10p11607.htm

CSE
Shi X, Yang W, Ma Q, Lu Y, Xu Y, Bian K, Liu F, Shi C, Wang H, Shi Y, Zhang B. 2020. Hemoglobin-mediated biomimetic synthesis of paramagnetic O2-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor. Theranostics. 10(25):11607-11621.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Popup Image