In situ hypoxia modulating nano-catalase for amplifying DNA damage in radiation resistive colon tumors

被引：2

作者：

Kim, Subin ^{[1
,2
,7
,8
]}

Sundaram, Aravindkumar ^{[1
,2
]}

Mathew, Ansuja Pulickal ^{[1
,2
]}

Hareshkumar, Vasvani Shyam ^{[1
,2
,7
,8
]}

Mohapatra, Adityanarayan ^{[1
,2
]}

Thomas, Reju George ^{[3
,4
]}

Bui, Thinh T. M. ^{[5
]}

Moon, Kyuho ^{[5
]}

Kweon, Seho ^{[6
]}

Park, In-Kyu ^{[1
,2
,7
,8
]}

Jeong, Yong Yeon ^{[3
,4
,8
]}

机构：

[1] Chonnam Natl Univ, Med Sch, Dept Biomed Sci, Gwangju 61469, South Korea

[2] Chonnam Natl Univ, Med Sch, Biomed Sci Grad Program BMSGP, Gwangju 61469, South Korea

[3] Chonnam Natl Univ, Med Sch, Dept Radiol, Hwasun 58128, South Korea

[4] Hwasun Hosp, Hwasun 58128, South Korea

[5] Chonnam Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Gwangju, South Korea

[6] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul 08826, South Korea

[7] Chonnam Natl Univ, Med Sch, Ctr Global Future Biomed Sci, Hwasun 58128, South Korea

[8] DR Cure Inc, Hwasun 58128, South Korea

来源：

BIOMATERIALS SCIENCE | 2023年 / 11卷 / 18期

基金：

新加坡国家研究基金会;

关键词：

RADIOTHERAPY; CANCER; THERAPY; NANOPARTICLES; OPPORTUNITIES; CHALLENGES; DELIVERY; IMPACT;

D O I：

10.1039/d3bm00618b

中图分类号：

TB3 [工程材料学]; R318.08 [生物材料学];

学科分类号：

0805 ; 080501 ; 080502 ;

摘要：

Radiation therapy (RT) is a mainstream clinical approach in cancer treatment. However, the therapeutic efficacy of RT is greatly hindered by the presence of excessive hydrogen peroxide (H2O2) in the hypoxic region of the solid tumor, thus leading to tumor recurrence and metastasis. Herein, a thioketal-linked amphiphilic nano-assembly (MTS) loaded with hydrophobic manganese oxide (HMO) nanoparticles (MTS@HMO) is examined as a promising multi-purpose reactive oxygen species (ROS)-catalytic nanozyme for transforming an RT-resistant hypoxic tumor microenvironment (TME) into an RT-susceptible one by scavenging ROS in the hypoxic core of the solid tumor. After intravenous injection, the MTS@HMO nano-assembly was able to sense and be degraded by the abundant ROS in the hypoxic TME, thereby releasing HMO particles for subsequent scavenging of H2O2. The oxygen generated during peroxide scavenging then relieved the hypoxic TME, thereby resulting in an increased sensitivity of the hypoxic tumor tissue towards RT. Moreover, the in situ hypoxic status was monitored via the T1-enhanced magnetic resonance (MR) imaging of the Mn2+ ions generated by the ROS-mediated degradation of HMO. The in vitro results demonstrated a significant H2O2 elimination and enhanced oxygen generation after the treatment of the MTS@HMO nano-assembly with tumor cells under hypoxic conditions, compared to the control MTS group. In addition, the combination of RT and pre-treatment with MTS@HMO nano-assembly significantly amplified the permanent DNA strand breaks in tumor cells compared to the control RT group. More importantly, the in vivo results proved that the systemic injection of the MTS@HMO nano-assembly prior to RT irradiation enhanced the RT-mediated tumor suppression and down-regulated the hypoxic marker of HIF-1 & alpha; in the solid tumor compared to the control RT group. Overall, the present work demonstrates the great potential of the versatile ROS-catalytic hypoxia modulating strategy using the MTS@HMO nano-assembly to enhance the RT-induced antitumor efficacy in hypoxic solid tumors.

引用

页码：6177 / 6192

页数：16