Construction and application of microneedle-mediated photothermal therapy and immunotherapy combined anti-tumor drug delivery system

Abstract

Conventional treatments for tumors were frequently accompanied by drawbacks and side effects. It might be useful to use the revolutionary microneedle technology which combines photothermal therapy with tumor immunotherapy. In this study, we created a microneedle drug delivery system with mercapto-modified gold nanorods and immune checkpoint blocker anti-PD-1 polypeptide. With good mechanical strength, the microneedle system can efficiently penetrate the skin and deliver drugs. When inserted into human skin, anti-PD-1 peptides and gold nanorods can be released, boosting the capacity of cytotoxic T lymphocytes to destroy tumor cells. Additionally, the elimination of the tumor is aided by the production of heat while being exposed to near-infrared light. This microneedle drug delivery system can enhance the immunological reaction and prolong the survival time of mice. Moreover, it has been demonstrated that the system has mild toxic and side effects on normal tissues and can effectively inhibit the growth of tumors, indicating a bright prospect for the treatment of cancers.

GRAPHICAL ABSTRACT

Keywords:

• Cancer immunotherapy
• photothermal therapy
• transcutaneous immunization
• dissolving microneedles

Authors’ contributions

Jiaqi Weng, Gensuo Zheng, Jiaoli Wen, Qinying Yan – supported with synthesis, characterization, molecular and biochemical analysis, data curation, formal analysis, and validation. Jing Yang, Xi Zheng – supported with synthesis, characterization, formal analysis, and validation. Qingliang Yang – review and editing. Qinying Yan, Qingliang Yang – helped with supervising the research. The manuscript was written through the contributions of all authors and was approved by all authors.

Availability of data and materials

All data generated or analyzed during this study are included in this submitted article. The raw data will be made available on request.

Consent for publication

All authors consent for publication.

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethics approval and consent to participate

The goal of the current study was to eliminate tumors by stimulating the body’s immune system. There are no substitutes for mimicking the immune system at the moment because of its complexity. The most efficient and necessary method in this investigation to confirm the therapeutic effect of the microneedle delivery device on tumor immunity is therefore animal model validation. In our study, 80 4 ∼ 6-week BALB/c mice were supplied by the Zhejiang Academy of Medical Sciences (Zhejiang, China) and carefully housed in the Laboratory Animal Center of Zhejiang University of Technology (Zhejiang, China) under constant temperature and humidity. All mice were utilized in vivo experiments after being given Isoflurane anesthesia.These experiments were approved by Zhejiang University of Technology Laboratory Animal Ethics Committee, affiliated to Zhejiang University of Technology (Approval number, 20211018081), and at the conclusion of the study, all mice were decollated and put to death. All animal experiments were performed following the ARRIVE guidelines.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [12104400]; the Major Scientific and Technological Innovation Projects of Wenzhou [ZY2021026]; the 2021 Open Project from Zhejiang Key Laboratory of Quality Control of Pharmaceutical Contact Materials [ZJYJ2021062301].