International Journal of Nanomedicine (Jan 2020)

Hypoxia-Targeting Multifunctional Nanoparticles for Sensitized Chemotherapy and Phototherapy in Head and Neck Squamous Cell Carcinoma

  • Song C,
  • Tang C,
  • Xu W,
  • Ran J,
  • Wei Z,
  • Wang Y,
  • Zou H,
  • Cheng W,
  • Cai Y,
  • Han W

Journal volume & issue
Vol. Volume 15
pp. 347 – 361

Abstract

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Chuanhui Song, 1, 2,* Chuanchao Tang, 1, 2,* Wenguang Xu, 2 Jianchuan Ran, 1, 2 Zheng Wei, 1, 3 Yufeng Wang, 1, 2 Huihui Zou, 1, 2 Wei Cheng, 4 Yu Cai, 1 Wei Han 1, 2 1Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, People’s Republic of China; 3Pediatric Dentistry, Nanjing Stomatology Hospital, Medical School of Nanjing University, Nanjing 210008, People’s Republic of China; 4Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing 210008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei ChengDepartment of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, No. 30 Zhongyang Road, Nanjing 210008, People’s Republic of ChinaTel +86-025-83620238Email [email protected] Wei HanDepartment of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing 210008, People’s Republic of ChinaTel +86-025-83620349Email [email protected]: Chemotherapy in head and neck squamous cell carcinoma (HNSCC) has many systemic side effects, as well as hypoxia-induced chemoresistance. To reduce side effects and enhance chemosensitivity are urgently needed.Methods: We synthesized a drug delivery system (named CECMa NPs) based on cisplatin (CDDP) and metformin (chemotherapeutic sensitizer), of which chlorin e6 (Ce6) and polyethylene glycol diamine (PEG) were synthesized as the shell, an anti-LDLR antibody (which can target to hypoxic tumor cells) was modified on the surface to achieve tumor targeting.Results: The NPs possessed a great synergistic effect of chemotherapy and phototherapy. After laser stimulation, both CDDP and metformin can be released in situ to achieve anti-tumor effects. Meanwhile, PDT and PTT triggered by a laser have anticancer effects. Furthermore, compared with free cisplatin, CECMa exhibits less systemic toxicity with laser irradiation in the xenograft mouse tumor model.Conclusion: CECMa effectively destroyed the tumors via hypoxia targeting multimodal therapy both in vitro and in vivo, thereby providing a novel strategy for targeting head and neck squamous cell carcinoma.Keywords: cisplatin, metformin, chlorin e6, head and neck squamous cell carcinoma, nano-delivery

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