Tumor microenvironment-responsive nanohybrid for hypoxia amelioration with photodynamic and near-infrared II photothermal combination therapy

Pengli Zhang; Qinghe Wu; Jingxing Yang; Mengfei Hou; Benchao Zheng; Jia Xu; Yimin Chai; Liqin Xiong; Chunfu Zhang

doi:10.1016/j.actbio.2022.04.044

Tumor microenvironment-responsive nanohybrid for hypoxia amelioration with photodynamic and near-infrared II photothermal combination therapy

Acta Biomater. 2022 Jul 1:146:450-464. doi: 10.1016/j.actbio.2022.04.044. Epub 2022 May 6.

Authors

Pengli Zhang¹, Qinghe Wu¹, Jingxing Yang¹, Mengfei Hou¹, Benchao Zheng¹, Jia Xu¹, Yimin Chai¹, Liqin Xiong¹, Chunfu Zhang²

Affiliations

¹ Department of Orthopedics, Shanghai Jiao Tong University Affiliated 6th Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
² Department of Orthopedics, Shanghai Jiao Tong University Affiliated 6th Hospital, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: cfzhang@sjtu.edu.cn.

PMID: 35526739
DOI: 10.1016/j.actbio.2022.04.044

Abstract

Phototherapy, particularly photothermal therapy (PTT) and photodynamic therapy (PDT), has been widely investigated for tumor treatment. However, the limited tissue penetration depth of light in the near-infrared I (NIR-I) region and the hypoxic tumor microenvironment (TME) severely constrain their clinical applications. To address these challenges, in the present study, we developed a chlorin e6 (Ce6) and MnO₂-coloaded, hyaluronic acid (HA)-coated single-walled carbon nanohorns (SWNHs) nanohybrid (HA-Ce6-MnO₂@SWNHs) for PDT and PTT combination therapy of tumor. HA-Ce6-MnO₂@SWNHs responded to the mild acidic TME to ameliorate tumor hypoxia, thus enhancing tumor PDT. Moreover, HA-Ce6-MnO₂@SWNHs had a high photothermal conversion efficiency at 1064 nm (55.48%), which enabled deep tissue penetration (3.05 cm) and allowed for highly efficient tumor PTT in near-infrared II (NIR-II) window. PDT and PTT combination therapy with HA-Ce6-MnO₂@SWNHs achieved a good therapeutic efficacy on 4T1 tumor-bearing mice, eradicating the primary tumors and suppressing cancer recurrence. Our study provides a promising strategy for developing a hypoxia relief and deep tissue penetration phototherapy platform by using SWNHs for highly effective tumor PDT and NIR-II PTT combination therapy. STATEMENT OF SIGNIFICANCE: The hypoxic tumor microenvironment (TME) and the limited penetration of the NIR-I light in biological tissues compromise the efficacy of photothermal therapy (PTT) and photodynamic therapy (PDT) on tumors. Here, we developed a chlorin e6 (Ce6) and MnO₂-coloaded, hyaluronic acid (HA)-coated single-walled carbon nanohorns (SWNHs) nanohybrid (HA-Ce6-MnO₂@SWNHs) for PDT and PTT combination therapy of tumors. The nanohybrid could efficiently accumulate in tumors through CD44-mediated active targeting. The sequential MnO₂-enhanced PDT and efficient NIR-II PTT had a remarkable therapeutic effect by eliminating the primary tumor and simultaneously inhibiting tumor recurrence.

Keywords: Combined phototherapy; Near-infrared II window; Photodynamic therapy; Photothermal therapy; Tumor hypoxia.

Publication types

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

MeSH terms

Animals
Carbon
Cell Line, Tumor
Hyaluronic Acid / pharmacology
Hypoxia / therapy
Manganese Compounds / pharmacology
Mice
Nanoparticles*
Neoplasms* / drug therapy
Oxides / pharmacology
Photochemotherapy*
Photosensitizing Agents / pharmacology
Photosensitizing Agents / therapeutic use
Photothermal Therapy
Tumor Microenvironment

Substances

Manganese Compounds
Oxides
Photosensitizing Agents
Carbon
Hyaluronic Acid