ICG-Loaded PEG-Modified Black Phosphorus Nanosheets for Fluorescence Imaging-Guided Breast Cancer Therapy

Wanwan Pan; Weijian Chen; Yuanzeng Min; Jing Wang; Zhenye Yang; Tian Xu; Fazhi Yu; Guodong Shen; Yuan Hu; Xiaopeng Ma

doi:10.1021/acsomega.1c04909

ICG-Loaded PEG-Modified Black Phosphorus Nanosheets for Fluorescence Imaging-Guided Breast Cancer Therapy

ACS Omega. 2021 Dec 15;6(51):35505-35513. doi: 10.1021/acsomega.1c04909. eCollection 2021 Dec 28.

Authors

Wanwan Pan¹, Weijian Chen², Yuanzeng Min³, Jing Wang¹, Zhenye Yang⁴, Tian Xu⁴, Fazhi Yu⁴, Guodong Shen⁵, Yuan Hu², Xiaopeng Ma¹

Affiliations

¹ Department of Thyroid and Breast Surgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230036, Anhui, P. R. China.
² State Key Laboratory of Fire Science, University of Science and Technology of China, Hefei 230026, Anhui, P. R. China.
³ CAS Key Laboratory of Soft Matter Chemistry, Department of Chemistry, Department of Bio-X Interdisciplinary Science at Hefei National Laboratory (HFNL) for Physical Science at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, P. R. China.
⁴ Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, Anhui, P. R. China.
⁵ Department of Geriatrics, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230036, Anhui, P. R. China.

Abstract

Indocyanine green (ICG) has been used in various surgical navigation systems and plays an important role in intraoperative imaging diagnosis. However, the poor photostability and unsatisfactory tumor-targeting ability have limited its broad application prospects. In the decades, the construction of a nanodrug delivery system for tumor-targeting diagnosis and therapy has become a research hotspot. Black phosphorus nanosheets (BPNS), as a new kind of biodegradable nanomaterials, have the advantages of high loading capacity, good biocompatibility, tumor targeting, and photothermal effect over other two-dimensional (2D) reported nanomaterials. Herein, ICG-loaded poly(ethylene glycol) (PEG)-modified BPNS (ICG@BPNS-PEG) nanocomposites are constructed to improve the tumor-targeting capacity and guide photothermal therapy through real-time fluorescence imaging. In this study, ICG@BPNS-PEG nanocomposites with a suitable size (240 ± 28 nm) have been successfully constructed. The photostability of ICG@BPNS-PEG nanocomposites surpassed that of free ICG after four on-off cycles of near laser irradiation (NIR). Moreover, ICG@BPNS-PEG nanocomposites have enhanced photothermal conversion ability. The cellular uptake result through flow cytometry showed that ICG@BPNS-PEG nanocomposites could be swallowed easily owing to the suitable size and passive cellular uptake. In addition, the cytotoxicity evaluation of MCF-7, 4T1 breast cancer cells, and healthy RPE cells through the MTT assay demonstrated that ICG@BPNS-PEG nanocomposites have lower cytotoxicity and good cellular compatibility without irradiation. However, the cytotoxicity and live/dead staining proved that ICG@BPNS-PEG nanocomposites have satisfactory photothermal therapeutic effects when irradiated. In the 4T1-bearing mice model, the fluorescence imaging after intravenous injection of nanocomposites showed that ICG@BPNS-PEG nanocomposites have superior passive tumor targeting accumulation through the enhanced permeability and retention (EPR) effect compared with that of free ICG. Also, changes in tumor volume showed a remarkable tumor growth inhibition effect compared with other groups. Moreover, the results of hematoxylin-eosin (H&E) staining of major organs in 4T1-bearing mice also demonstrated that the nanocomposites have good biocompatibility. Therefore, the constructed ICG@BPNS-PEG nanocomposites have substantial potential in breast cancer therapy.