Magnetic Resonance/Infrared Dual-Modal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy Nanoplatform Based on Cu1.96S-Gd@FA for Precision Cancer Theranostics

Lixin Cheng; Dongmiao Sang; Fangyu Zhao; Lili Yang; Zhilin Guo; Xinfeng Zhang; Qiaoqiao Yang; Wenju Qiao; Xiaohong Sun; Xiaohong Guan; Haoyu Wang; Jiannan Wang; Hongyan Zou; Xiu'e Li; Fang Fang; Yang Li; Shujun Zhang; Lina Wu; Huiming Lin; Xilin Sun; Kai Wang

doi:10.1016/j.jcis.2022.01.099

Magnetic Resonance/Infrared Dual-Modal Imaging-Guided Synergistic Photothermal/Photodynamic Therapy Nanoplatform Based on Cu_1.96S-Gd@FA for Precision Cancer Theranostics

J Colloid Interface Sci. 2022 Jun:615:95-109. doi: 10.1016/j.jcis.2022.01.099. Epub 2022 Jan 20.

Authors

Lixin Cheng¹, Dongmiao Sang², Fangyu Zhao², Lili Yang³, Zhilin Guo², Xinfeng Zhang³, Qiaoqiao Yang³, Wenju Qiao³, Xiaohong Sun³, Xiaohong Guan³, Haoyu Wang³, Jiannan Wang², Hongyan Zou², Xiu'e Li², Fang Fang³, Yang Li⁴, Shujun Zhang⁵, Lina Wu³, Huiming Lin⁶, Xilin Sun⁷, Kai Wang⁸

Affiliations

¹ NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin,150028, China; Health Management Center, the Fourth Hospital of Harbin Medical University, Harbin,150028, China.
² NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin,150028, China.
³ NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin,150028, China; Department of Nuclear Medicine, the Fourth Hospital of Harbin Medical University, Harbin,150028, China.
⁴ Department of Cardiology, the Fourth Hospital of Harbin Medical University, Harbin,150000, China.
⁵ Department of Pathology, the Fourth Hospital of Harbin Medical University, Harbin,150000, China.
⁶ Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, Heilongjiang Province and College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin, 150025, China. Electronic address: linhuiming@hrbnu.edu.cn.
⁷ NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin,150028, China; Department of Nuclear Medicine, the Fourth Hospital of Harbin Medical University, Harbin,150028, China. Electronic address: sunxl@ems.hrbmu.edu.cn.
⁸ NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin,150028, China; Department of Nuclear Medicine, the Fourth Hospital of Harbin Medical University, Harbin,150028, China. Electronic address: wangkai@hrbmu.edu.cn.

PMID: 35124510
DOI: 10.1016/j.jcis.2022.01.099

Abstract

Developing new nanoplatforms for dynamically and quantitatively visualizing drug accumulation and targeting within tumors is crucial for precision cancer theranostic. However, achieving efficient tumor therapy via synergistic photothermal/photodynamic therapy (PTT/PDT) using a single excitation light source, remains a challenge. In this work, we designed Gd-surface functionalized copper sulfide nanoparticles that were modified with folic acid (FA) (Cu_1.96S-Gd@FA) to overcome the above limitations and promote PTT/PDT therapeutics. Here, Cu_1.96S-Gd nanoparticles were synthesized via a coprecipitation method. All samples exhibited high longitudinal relaxivity (up to 12.9 mM^-1 s^-1) and strong photothermal conversion efficiency (50.6%). Furthermore, the Gd ions promoted electron-hole segregation, inducing the Cu_1.96S-Gd nanoparticles to generate more reactive oxygen species (ROS) than pure Cu_1.96S nanoparticles. The Cu_1.96S-Gd@FA enabled the targeting of folate receptor (FR) and promoted cellular uptake, consequently enhancing oncotherapy efficacy. Compared to non-targeted Cu_1.96S-Gd, a higher signal enhancement for magnetic resonance (MR) imaging in vivo by Cu_1.96S-Gd@FA was recorded. Given photothermal ability, the nanoparticles also could be visualized in infrared (IR) imaging. Furthermore, the nanoparticles exhibited biodegradation behavior and achieved good drug elimination performance via renal clearance. Our strategy, integrating Cu_1.96S-Gd@FA nanoparticles, MR/IR dual-modal imaging, and PTT/PDT into one nanoplatform, demonstrated great potential for anti-breast cancer therapy by effectively targeting FR overexpressed breast cancer cells.

Keywords: Breast Cancer; Copper Sulfide (Cu(1.96)S) Nanoplatform; Drug Elimination; Folate Receptor (FR); Magnetic Resonance/Infrared (MR/IR) Imaging; Oncotherapy; Photothermal/Photodynamic Therapy (PTT/PDT); Precision Cancer Theranostics.

MeSH terms

Breast Neoplasms* / diagnostic imaging
Breast Neoplasms* / drug therapy
Cell Line, Tumor
Female
Folic Acid / metabolism
Humans
Magnetic Resonance Imaging
Magnetic Resonance Spectroscopy
Nanoparticles*
Photochemotherapy* / methods
Phototherapy
Precision Medicine

Substances

Folic Acid