Nanoradiosensitizer with good tissue penetration and enhances oral cancer radiotherapeutic effect

Di Jing; Nian Jiang; Fengyi Wang; Chunping Mao; Shujun Han; Pui Yan Ho; Wenwu Xiao; Yuanpei Li; Jian Jian Li; Lu Zhang; Kit S Lam

doi:10.1016/j.biomaterials.2022.121769

Nanoradiosensitizer with good tissue penetration and enhances oral cancer radiotherapeutic effect

Biomaterials. 2022 Oct:289:121769. doi: 10.1016/j.biomaterials.2022.121769. Epub 2022 Sep 1.

Authors

Di Jing¹, Nian Jiang², Fengyi Wang³, Chunping Mao³, Shujun Han⁴, Pui Yan Ho⁵, Wenwu Xiao⁵, Yuanpei Li⁵, Jian Jian Li⁴, Lu Zhang⁶, Kit S Lam⁷

Affiliations

¹ Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA; Department of Oncology, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China.
⁴ Department of Radiation Oncology, School of Medicine, University of California Davis, Sacramento, CA, USA.
⁵ Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA.
⁶ Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, Guangdong, China. Electronic address: [email protected].
⁷ Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA, USA; Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, USA. Electronic address: [email protected].

Abstract

Low dose non-toxic disulfide cross-linked micelle (DCM) encapsulated paclitaxel (PTX) was found to be highly efficacious as a radiosensitizer against oral cancer preclinical model. Intensity-modulated radiation therapy was locally administered for three consecutive days 24 h after intravascular injection of DCM-[PTX] at 5 mg/kg PTX. DCM-[PTX] NPs combined with conventional radiotherapy (2 Gy) resulted in a 1.7-fold improvement in therapeutic efficacy compared to conventional PTX plus radiotherapy. Interestingly, we found that radiotherapy can decrease tight junctions and increase the accumulation of DCM-[PTX] in tumor sites. Stereotactic body radiotherapy (SBRT) given at 6 Gy was used to further investigate the synergistic anti-tumor effect. Tumor tissues were collected to analyze the relationship between the time interval after SBRT and the biodistribution of the nanomaterials. Compared to combination DCM-[PTX] with conventional radiation dose, combination DCM-PTX with SBRT was found to be more efficacious in inhibiting tumor growth.

Keywords: Nano-micelle; Oral cancer; Radio-sensitizer; Radiotherapy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Disulfides
Humans
Micelles*
Mouth Neoplasms* / drug therapy
Mouth Neoplasms* / radiotherapy
Paclitaxel / pharmacology
Paclitaxel / therapeutic use
Tissue Distribution

Substances

Disulfides
Micelles
Paclitaxel

Abstract

Publication types

MeSH terms

Substances

Grants and funding