Citation: Hongyi Huang, Siyao Che, Wenjie Zhou, Yunchu Zhang, Weiling Zhuo, Xijing Yang, Songping Zheng, Jiagang Liu, Xiang Gao. Apatinib potentiates doxorubicin with cRGD-functionalized pH-sensitive micelles against glioma[J]. Chinese Chemical Letters, ;2025, 36(5): 110084. doi: 10.1016/j.cclet.2024.110084 shu

Apatinib potentiates doxorubicin with cRGD-functionalized pH-sensitive micelles against glioma

Hongyi Huang ^{a, 1} ,
Siyao Che ^{a, 1} ,
Wenjie Zhou ^{b, c, 1} ,
Yunchu Zhang ^a ,
Weiling Zhuo ^a ,
Xijing Yang ^d ,
Songping Zheng ^{a, *,} ,
Jiagang Liu ^{a, *,} ,
Xiang Gao ^{a, *,}

a.
Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
b.
Department of Laboratory Medicine, West China Second University Hospital, Sichuan University, Chengdu 610041, China
c.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu 610041, China
d.
The Experimental Animal Center of West China Hospital Sichuan University, Chengdu 610041, China

zhengsongping2022@163.com

jiagang_liu@163.com

xianggao@scu.edu.cn

Received Date: 26 February 2024
Revised Date: 30 May 2024
Accepted Date: 3 June 2024
Available Online: 4 June 2024

Figures(5)

Glioma is a severe malignant brain tumor marked by an exceedingly dire prognosis and elevated incidence of recurrence. The resilience of such tumors to chemotherapeutic agents, coupled with the formidable obstacle the blood-brain barrier (BBB) presents to most pharmacological interventions are major challenges in anti-glioma therapy. In an endeavor to surmount these impediments, we have synergized pH-sensitive nanoparticles carrying doxorubicin and apatinib to amplify the anti-neoplastic efficacy with cyclic arginine–glycine–aspartate acid (cRGD) modification. In this study, we found that the combination of doxorubicin (DOX) and apatinib (AP) showed a significant synergistic effect, achieved through cytotoxicity and induction of apoptosis, which might be due to the increased intracellular uptake of DOX following AP treatment. Besides, polycaprolactone-polyethylene glycol-cRGD (PCL-PEG-cRGD) drug carrier could cross the BBB by its targeting ability, and then deliver the drug to the glioma site via pH-responsive release, increasing the concentration of the drugs in the tumor. Meanwhile, DOX/AP-loaded PCL-PEG-cRGD nanoparticles effectively inhibited cell proliferation, enhanced glioma cell apoptosis, and retarded tumor growth in vivo. These results collectively identified DOX/AP-loaded PCL-PEG-cRGD nanoparticles as a promising therapeutic candidate for the treatment of glioma.
- Apatinib,
- Doxorubicin,
- Glioma,
- Nanomicelle,
- Co-delivery
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