A generic self-assembly approach towards phototheranostics for NIR-II fluorescence imaging and phototherapy

Cao Cui; Chenlu Wang; Qinrui Fu; Jibin Song; Jianhua Zou; Ling Li; Jianwei Zhu; Wei Huang; Lin Li; Zhen Yang; Xiaoyuan Chen

doi:10.1016/j.actbio.2021.11.023

A generic self-assembly approach towards phototheranostics for NIR-II fluorescence imaging and phototherapy

Acta Biomater. 2022 Mar 1:140:601-609. doi: 10.1016/j.actbio.2021.11.023. Epub 2021 Nov 20.

Authors

Cao Cui¹, Chenlu Wang², Qinrui Fu², Jibin Song², Jianhua Zou³, Ling Li³, Jianwei Zhu⁴, Wei Huang⁵, Lin Li⁶, Zhen Yang⁷, Xiaoyuan Chen⁸

Affiliations

¹ Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Hubei 441021, China.
² MOE key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou 350108, China.
³ Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, 119074, Singapore; Clinical Imaging Research Center, Center for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117599, Singapore; Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.
⁴ School of Pharmaceutical Sciences, Nanjing Tech University, 30 South Puzhu Road, Nanjing 211816, China. Electronic address: jianweizhu@njtech.edu.cn.
⁵ Fujian Cross Strait Institute of Flexible Electronics (Future Technologies), Fujian Normal University, Fuzhou 350117, China; Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials and Engineering, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, PR China.
⁶ Frontiers Science Center for Flexible Electronics, Xi'an Institute of Flexible Electronics (IFE) and Xi'an Institute of Biomedical Materials and Engineering, Northwestern Polytechnical University, 127 West Youyi Road, Xi'an 710072, PR China. Electronic address: iamlli@nwpu.edu.cn.
⁷ Fujian Cross Strait Institute of Flexible Electronics (Future Technologies), Fujian Normal University, Fuzhou 350117, China. Electronic address: ifezhyang@fjnu.edu.cn.
⁸ Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, 119074, Singapore; Clinical Imaging Research Center, Center for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 117599, Singapore; Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore. Electronic address: chen.shawn@nus.edu.sg.

PMID: 34808416
DOI: 10.1016/j.actbio.2021.11.023

Abstract

Controllable self-assembly of photonic molecules for precise biomedicine is highly desirable but challenging to prepare multifunctional nano-phototheranostics. Herein, we developed a generic self-assembly approach to design nano-phototheranostics that provides NIR-II fluorescence imaging and phototherapy. We first designed and synthesized two amphiphilic photonic molecules, PEG₂₀₀₀-IR806 and BODIPY. Then, we prepared the co-self-assembled phototheranostic agents, PEG₂₀₀₀-IR806/BODIPY nanoparticles (PIBY NPs). The morphology of the PIBY NPs is controllable by adjusting the ratio of PEG₂₀₀₀-IR806 and BODIPY during self-assembly. The NIR-II fluorescence properties and phototherapy capability of the PIBY NPs were demonstrated in vitro and in vivo. By tuning the ratio of PEG₂₀₀₀-IR806 and BODIPY, the PIBY NPs showed various morphologies (e.g. spherical nanoparticles, nanovesicles and rod-like nanoparticles). The PEG₂₀₀₀-IR806 plays two roles in the co-self-assemblies, one is second near-infrared (NIR-II, 1000-1700 nm) agent, the other is the surfactant for BODIPY encapsulation. The phototherapeutic PIBY NPs all show bright NIR-II fluorescence and effective phototherapeutic (photothermal and photodynamic) properties, which are attributed to IR806 and BODIPY, respectively. The driving force of the self-assembly can be attributed to the electrostatic interaction between NIR806 and BODIPY and their hydrophobicity. The rod-like PIBY NPs (rPIBY NPs) demonstrated a low half inhibitory concentration (IC₅₀) of 3.96 µg/mL on U87MG cells. The NIR-II imaging showed the accumulation of rPIBY NPs in the tumor region. After systemic injection of rPIBY NPs at low dose (0.5 mg/kg), the tumor growth was greatly inhibited upon laser irradiation without noticeable side effects. This study provides a generic self-assembly approach to fabricate NIR-II imaging and phototherapeutic platform for cancer phototheranostics. STATEMENT OF SIGNIFICANCE: Nanophototheranostics providing NIR-II fluorescence imaging and phototherapy are expected to play a critical role in modern precision medicine. Controllable self-assembly of optical molecules for the fabrication of efficient nanophototheranostics is highly desirable but challenging. This work reports for the first time the co-assembly of a NIR-II imaging contrast agent and a phototherapeutic agent to yield nanophototheranostics with various morphologies. The design of molecular co-assembly with complementary optical functions can be a generic method for future the development of phototheranostics.

Keywords: NIR-II fluorescence imaging; Photodynamic therapy; Phototheranostics; Photothermal therapy; Self-assembly.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Humans
Nanoparticles* / therapeutic use
Neoplasms*
Optical Imaging
Phototherapy
Precision Medicine
Theranostic Nanomedicine / methods