Neutrophils mediated multistage nanoparticle delivery for prompting tumor photothermal therapy

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Journal of Nanobiotechnology Open Access

RESEARCH

Neutrophils mediated multistage nanoparticle delivery for prompting tumor photothermal therapy Bo Ye1†, Bao Zhao2†, Kun Wang3†, Yilong Guo4, Qinguo Lu4, Longpo Zheng5*, Ang Li6* and Jianou Qiao7*

Abstract  Background:  Neutrophil-based drug delivery system possesses excellent advantages in targeting at tumour because neutrophils are easily recruited by chemotactic factor in tumor microenvironment. Herein, we developed a novel tactic of multistage neutrophils-based nanoparticle delivery system for promoting photothermal therapy (PTT) of lung cancer. Results:  Au nanorod (AuNR) was successfully modified with bovine serum albumin (AuNRB) and further conjugated with RGD (AuNRBR), followed by neutrophil internalisation to obtain neutrophils-based delivery system (AuNRBR/N). The engineered neutrophils efficiently migrated across the epithelial cells due to inflammatory signal. They exhibited better toxicity against Lewis cells with laser irradiation in vitro. Moreover, AuNRBR/N showed significantly more targetability to tumour tissue compared with cell carrier-free AuNRBR, as demonstrated in Lewis tumour-bearing mice. The enhanced tumour homing efficiency of AuNRBR/N together with subsequently released AuNRBR from the neutrophils was favourable for further deep tissue diffusion and contributed to the inhibition of the tumour growth in PTT and improved survival rate (over 120 days). Conclusions:  Overall results illustrated that the design of cell-based nanoparticle delivery system for PTT of cancer is promising. Keywords:  Neutrophils, Photothermal therapy, Inflammatory signal, Au nanorod, Tumour homing

Background Photothermal therapy (PTT) is a promising treatment modality for the improvement of cancer therapy, especially for some epidermomas, such as melanoma and breast cancer. Photosensitisers are typically used to *Correspondence: [email protected]; [email protected]; qjou@163. com † Bo Ye, Bao Zhao, Kun Wang equally contribute to the article 5 Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai 200072, People’s Republic of China 6 School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, People’s Republic of China 7 Department of Respiratory Medicine, Shanghai Ninth Peoples Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd, Shanghai 200011, China Full list of author information is available at the end of the article

generate hyperthermia for the elimination of tumour under near-infrared (NIR) irradiation whilst minimising thermal diffusion to normal tissue. Au nanorod (AuNR) with strong NIR absorption was widely studied recently for the presence of plasmonic nanostructures, which serve as highly localised heat sources under NIR irradiation through the photothermal effect [1]. However, systemic administration of AuNR faced many challenges, including poor distribution in  vivo and less efficient accumulation within the tumour, which lead to undesired hyperthermia. Nanoparti