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Nucleus-Targeted Photosensitizer Nanoparticles for Photothermal and Photodynamic Therapy of Breast Carcinoma

Authors Liu J, Yin Y, Yang L, Lu B, Yang Z, Wang W, Li R

Received 29 September 2020

Accepted for publication 24 December 2020

Published 22 February 2021 Volume 2021:16 Pages 1473—1485


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster

Jing Liu,1,* Yaru Yin,1,* Luxun Yang,1 Binghui Lu,1 Zhangyou Yang,2 Weidong Wang,3 Rong Li1

1Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Military Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing, 400038, People’s Republic of China; 2Department of Pharmacy, Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 3Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, 610041, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Weidong Wang
Sichuan Cancer Hospital, Renmin South Road, Chengdu, 610041, Sichuan, People’s Republic of China
Rong Li
Army Medical University, No 30, Gaotanyan St., Chongqing, 400038, People’s Republic of China
Tel +86-13883996627
Fax +86023-68753127

Purpose: The near-infrared fluorescent dye indocyanine green (ICG) has shown great potential in the photodynamic therapy (PDT) and photothermal therapy (PTT) of cancer. However, its disadvantages of instability in aqueous solution, short half-life, and non-targeting accumulation limit the effectiveness of ICG PDT/PTT. To overcome the disadvantages of ICG in tumor treatment, we designed PEGylated-human serum albumin (PHSA)-ICG-TAT. In this nanoparticle, PEG4000, the HSA package, and nuclear targeting peptide TAT (human immunodeficiency virus 1 [HIV-1]-transactivator protein) were used to improve the water solubility of ICG, prolong the life span of ICG in vivo, and target the nuclei of tumor cells, respectively.
Methods: The PHSA-ICG-TAT was characterized in terms of morphology and size, ultraviolet spectrum, dispersion stability, singlet oxygen and cellular uptake, and colocalization using transmission electron microscopy and dynamic light scattering, and fluorescence assay, respectively. Subsequently, the anti-tumor effect of PHSA-ICG-TAT was investigated via in vitro and in vivo experiments, including cell viability, apoptosis, comet assays, histopathology, and inhibition curves.
Results: The designed ICG-loaded nanoparticle had a higher cell uptake rate and stronger PDT/PTT effect than free ICG. The metabolism of PHSA-ICG-TAT in normal mice revealed that there was no perceptible toxicity. In vivo imaging of mice showed that PHSA-ICG-TAT had a good targeting effect on tumors. PHSA-ICG-TAT was used for the phototherapy of tumors, and significantly suppressed the tumor growth. The tumor tissue sections showed that the cell gap and morphology of the tumor tissue had been obviously altered after treatment with PHSA-ICG-TAT.
Conclusion: These results indicate that the PHSA-ICG-TAT had a significant therapeutic effect against tumors.

Keywords: indocyanine green, human serum albumin, phototherapy, nuclear targeting

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