2. Academic Validation
  3. Efficiently targeted therapy of glioblastoma xenograft via multifunctional biomimetic nanodrugs

Efficiently targeted therapy of glioblastoma xenograft via multifunctional biomimetic nanodrugs

  • Biomater Res. 2022 Dec 2;26(1):71. doi: 10.1186/s40824-022-00309-y.
Zhipeng Yao # 1 2 3,  Xiaochun Jiang # 2,  Hong Yao # 4,  Yafeng Wu # 1,  Fan Zhang 3,  Cheng Wang 3,  Chenxue Qi 2 5,  Chenhui Zhao 2,  Zeyu Wu 2,  Min Qi 2,  Jia Zhang 2,  Xiaoxiang Cao 2,  Zhichun Wang 2,  Fei Wu 2,  Chengyun Yao 6,  Songqin Liu 7,  Shizhang Ling 8,  Hongping Xia 9 10 11 12 13
Affiliations

Affiliations

  • 1 School of Chemistry and Chemical Engineering & Interdisciplinary Innovation Institute for Medicine and Engineering, Southeast University, Nanjing, 211189, China.
  • 2 The Translational Research Institute for Neurological Disorders, Department of Neurosurgery of Wannan Medical College, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, People's Republic of China.
  • 3 Department of Pathology, Nanjing Drum Tower Hospital & Drum Tower Clinical College & Key Laboratory of Antibody Technique of National Health Commission & Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical University, Nanjing, 211166, China.
  • 4 The Department of Cancer Biotherapy Center& The Institute of Cancer Research, The Third Affiliated Hospital of Kunming Medical University & The Cancer Hospital of Yunnan province, Kunming, 650000, China.
  • 5 Department of Gynecologic Oncology, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China.
  • 6 Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing, 210009, China. yaochengyun@jszlyy.com.cn.
  • 7 School of Chemistry and Chemical Engineering & Interdisciplinary Innovation Institute for Medicine and Engineering, Southeast University, Nanjing, 211189, China. liusq@seu.edu.cn.
  • 8 The Translational Research Institute for Neurological Disorders, Department of Neurosurgery of Wannan Medical College, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, People's Republic of China. lingsz@hotmail.com.
  • 9 School of Chemistry and Chemical Engineering & Interdisciplinary Innovation Institute for Medicine and Engineering, Southeast University, Nanjing, 211189, China. xiahongping@njmu.edu.cn.
  • 10 The Translational Research Institute for Neurological Disorders, Department of Neurosurgery of Wannan Medical College, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, 241001, People's Republic of China. xiahongping@njmu.edu.cn.
  • 11 Department of Pathology, Nanjing Drum Tower Hospital & Drum Tower Clinical College & Key Laboratory of Antibody Technique of National Health Commission & Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical University, Nanjing, 211166, China. xiahongping@njmu.edu.cn.
  • 12 The Department of Cancer Biotherapy Center& The Institute of Cancer Research, The Third Affiliated Hospital of Kunming Medical University & The Cancer Hospital of Yunnan province, Kunming, 650000, China. xiahongping@njmu.edu.cn.
  • 13 Department of Gynecologic Oncology, Cancer Hospital of Shantou University Medical College, Shantou, 515041, China. xiahongping@njmu.edu.cn.
  • # Contributed equally.
PMID: 36461108 DOI: 10.1186/s40824-022-00309-y
Abstract

Background: Glioblastoma multiforme (GBM) is a fatal malignant primary brain tumor in adults. The therapeutic efficacy of chemotherapeutic drugs is limited due to the blood-brain barrier (BBB), poor drug targeting, and short biological half-lives. Multifunctional biomimetic nanodrugs have great potential to overcome these limitations of chemotherapeutic drugs.

Methods: We synthesized and characterized a biomimetic nanodrug CMS/PEG-DOX-M. The CMS/PEG-DOX-M effectively and rapidly released DOX in U87 MG cells. Cell proliferation and Apoptosis assays were examined by the MTT and TUNEL assays. The penetration of nanodrugs through the BBB and anti-tumor efficacy were investigated in the orthotopic glioblastoma xenograft models.

Results: We showed that CMS/PEG-DOX-M inhibited cell proliferation of U87 MG cells and effectively induced cell Apoptosis of U87 MG cells. Intracranial antitumor experiments showed that free DOX hardly penetrated the BBB, but CMS/PEG-DOX-M effectively reached the orthotopic intracranial tumor through the BBB and significantly inhibited tumor growth. Immunofluorescence staining of orthotopic tumor tissue sections confirmed that nanodrugs promoted Apoptosis of tumor cells. This study developed a multimodal nanodrug treatment system with the enhanced abilities of tumor-targeting, BBB penetration, and cancer-specific accumulation of chemotherapeutic drugs by combining chemotherapy and photothermal therapy. It can be used as a flexible and effective GBM treatment system and it may also be used for the treatment of other central nervous systems (CNS) tumors and extracranial tumors.

Keywords

Antitumor; Biomimetic; Doxorubicin; Glioblastoma; Nanodrug.

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