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

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

Received 3 October 2019

Accepted for publication 9 January 2020

Published 20 January 2020 Volume 2020:15 Pages 347—361

DOI https://doi.org/10.2147/IJN.S233294

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


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 work

Correspondence: Wei Cheng
Department of Oral Implantology, Nanjing Stomatological Hospital, Medical School of Nanjing University, No. 30 Zhongyang Road, Nanjing 210008, People’s Republic of China
Tel +86-025-83620238
Email dentist_nj@163.com

Wei Han
Department of Oral and Maxillofacial Surgery, Nanjing Stomatological Hospital, Medical School of Nanjing University, No 30 Zhongyang Road, Nanjing 210008, People’s Republic of China
Tel +86-025-83620349
Email doctorhanwei@hotmail.com

Purpose: 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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