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Research Article

A composite peptide-supramolecular microneedle system for melanoma immunotherapy

Mengzhen LiMinxuan WangLingyun LiLimin ZhangBing Ma( )Weizhi Wang( )
Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electro-photonic Conversion Materials, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China
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Abstract

Despite recent advances in melanoma treatment through the use of antibody immunotherapy, the clinical benefit remains restricted by its inefficient infiltration and immunosuppression within the tumor microenvironment (TME). In addition, immune-related adverse events (irAEs) have often occurred due to the off-target binding of therapeutic drugs to normal tissues after systematic administration. Herein, we constructed an integrated and cascaded drug delivery system for the treatment of melanoma. In addition to blocking the programmed cell death protein 1 or its ligand (PD-1/PD-L1) axis, the PD-L1 targeting peptide (FE) with spherical micelle self-assembly characteristics could also effectively encapsulate the immune adjuvant resiquimod (R848), and form a complete nano drug. FER was further integrated into tumor-responsive microneedles (MNs) to establish FER@MN and could reach the cascaded functions. FER could be sustainedly released from the MN system and disassemble into monomers, achieving PD-1/PD-L1 axis blockade whilst reprogramming the immunosuppressive TME. Notably, FER@MN permits the controllable release and retention enhancement of the targeting peptide in the TME, thus causing prolonged PD-L1 blockade effect. It is demonstrated that this synergistic treatment could efficiently inhibit melanoma growth, providing a new strategy for the combination treatment of melanoma.

Graphical Abstract

FE could self-assemble into nano micelles with an optimized self-assembly curvature through precisely controlling the ratios of hydrophobic tails and hydrophilic head surface. Immunologic adjuvants could be encapsulated in the nanovesicle (FER) through co-self-assembly to realize the programmed cell death protein 1 or its ligand (PD-1/PD-L1) blocking as well as the immune microenvironment activation simultaneously. In addition, a biodegradable microneedle (MN)-based transcutaneous delivery system was prepared to deliver FER for the treatment of melanoma. Importantly, MN could be degraded by specific enzymes in the tumor microenvironment to achieve sustained drug release towards the tumor sites.

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Nano Research
Pages 5335-5345

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Cite this article:
Li M, Wang M, Li L, et al. A composite peptide-supramolecular microneedle system for melanoma immunotherapy. Nano Research, 2023, 16(4): 5335-5345. https://doi.org/10.1007/s12274-022-5236-z
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Received: 24 August 2022
Revised: 18 October 2022
Accepted: 23 October 2022
Published: 31 December 2022
© Tsinghua University Press 2022