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Research Article

A composite peptide-supramolecular microneedle system for melanoma immunotherapy

Mengzhen Li, Minxuan Wang, Lingyun Li, Limin Zhang, Bing 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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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.

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.

Keywords

targeting peptidecascaded drug deliverymicroneedleimmune checkpoint blockadeself-assembly

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References

[1]

Häuser, W.; Ablin, J.; Fitzcharles, M. A.; Littlejohn, G.; Luciano, J. V.; Usui, C.; Walitt, B. Fibromyalgia. Nat. Rev. Dis. Primers 2015, 1, 15022.
Crossref Google Scholar
[2]

Bu, J.; Nair, A.; Iida, M.; Jeong, W. J.; Poellmann, M. J.; Mudd, K.; Kubiatowicz, L. J.; Liu, E. W.; Wheeler, D. L.; Hong, S. An avidity-based PD-L1 antagonist using nanoparticle-antibody conjugates for enhanced immunotherapy. Nano Lett. 2020, 20, 4901–4909.
Crossref Google Scholar
[3]

Zhang, X. D.; Wang, J. Q.; Chen, Z. W.; Hu, Q. Y.; Wang, C.; Yan, J. J.; Dotti, G.; Huang, P.; Gu, Z. Engineering PD-1-presenting platelets for cancer immunotherapy. Nano Lett. 2018, 18, 5716–5725.
Crossref Google Scholar
[4]

Nam, J.; Son, S.; Park, K. S.; Zou, W. P.; Shea, L. D.; Moon, J. J. Cancer nanomedicine for combination cancer immunotherapy. Nat. Rev. Mater. 2019, 4, 398–414.
Crossref Google Scholar
[5]

Topalian, S. L.; Taube, J. M.; Anders, R. A.; Pardoll, D. M. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer 2016, 16, 275–287.
Crossref Google Scholar
[6]

Sharma, P.; Hu-Lieskovan, S.; Wargo, J. A.; Ribas, A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017, 168, 707–723.
Crossref Google Scholar
[7]

Hu, M.; Zhang, J.; Yu, Y. L.; Tu, K.; Yang, T.; Wang, Y.; Hu, Q.; Kong, L.; Zhang, Z. P. Injectable liquid crystal formation system for reshaping tumor immunosuppressive microenvironment to boost antitumor immunity: Postoperative chemoimmunotherapy. Small 2020, 16, 2004905.
Crossref Google Scholar
[8]

Sun, M. Q.; Yao, S. B.; Fan, L. Y.; Fang, Z. G.; Miao, W. B.; Hu, Z. Y.; Wang, Z. H. Fibroblast activation protein-α responsive peptide assembling prodrug nanoparticles for remodeling the immunosuppressive microenvironment and boosting cancer immunotherapy. Small 2022, 18, 2106296.
Crossref Google Scholar
[9]

Jeong, W. J.; Choi, S. H.; Jin, K. S.; Lim, Y. B. Tuning oligovalent biomacromolecular interfaces using double-layered α-helical coiled-coil nanoassemblies from lariat-type building blocks. ACS Macro Lett. 2016, 5, 1406–1410.
Crossref Google Scholar
[10]

Lau, J. L.; Dunn, M. K. Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorg. Med. Chem. 2018, 26, 2700–2707.
Crossref Google Scholar
[11]

Yin, H. W.; Zhou, X. M.; Huang, Y. H.; King, G. J.; Collins, B. M.; Gao, Y. F.; Craik, D. J.; Wang, C. K. Rational design of potent peptide inhibitors of the PD-1: PD-L1 interaction for cancer immunotherapy. J. Am. Chem. Soc. 2021, 143, 18536–18547.
Crossref Google Scholar
[12]

Fu, L. P.; Zhang, J. H.; Wu, C. C.; Wang, W. Z.; Wang, D.; Hu, Z. Y.; Wang, Z. H. A novel PD-L1 targeting peptide self-assembled nanofibers for sensitive tumor imaging and photothermal immunotherapy in vivo. Nano Res. 2022, 15, 7286–7294.
Crossref Google Scholar
[13]

Zhang, C.; Gao, F.; Wu, W.; Qiu, W. X.; Zhang, L.; Li, R. Q.; Zhuang, Z. N.; Yu, W. Y.; Cheng, H.; Zhang, X. Z. Enzyme-driven membrane-targeted chimeric peptide for enhanced tumor photodynamic immunotherapy. ACS Nano 2019, 13, 11249–11262.
Crossref Google Scholar
[14]

Xiao, W. Y.; Wang, Y.; An, H. W.; Hou, D. Y.; Mamuti, M.; Wang, M. D.; Wang, J.; Xu, W. H.; Hu, L. M.; Wang, H. Click reaction-assisted peptide immune checkpoint blockade for solid tumor treatment. ACS Appl. Mater. Interfaces 2020, 12, 40042–40051.
Crossref Google Scholar
[15]

Zhang, L. G.; Su, T.; He, B.; Gu, Z. W. Self-assembly polyrotaxanes nanoparticles as carriers for anticancer drug methotrexate delivery. Nano-Micro Lett. 2014, 6, 108–115.
Crossref Google Scholar
[16]

Xia, X. L.; Yang, X. Y.; Huang, W.; Xia, X. X.; Yan, D. Y. Self-assembled nanomicelles of affibody-drug conjugate with excellent therapeutic property to cure ovary and breast cancers. Nano-Micro Lett. 2022, 14, 33.
Crossref Google Scholar
[17]

Dong, R. J.; Zhou, Y. F.; Huang, X. H.; Zhu, X. Y.; Lu, Y. F.; Shen, J. Functional supramolecular polymers for biomedical applications. Adv. Mater. 2015, 27, 498–526.
Crossref Google Scholar
[18]

Cheng, H.; Cheng, Y. J.; Bhasin, S.; Zhu, J. Y.; Xu, X. D.; Zhuo, R. X.; Zhang, X. Z. Complementary hydrogen bonding interaction triggered co-assembly of an amphiphilic peptide and an anti-tumor drug. Chem. Commun. 2015, 51, 6936–6939.
Crossref Google Scholar
[19]

Zou, R. F.; Wang, Q.; Wu, J. C.; Wu, J. X.; Schmuck, C.; Tian, H. Peptide self-assembly triggered by metal ions. Chem. Soc. Rev. 2015, 44, 5200–5219.
Crossref Google Scholar
[20]

Xu, L.; Shen, Q.; Huang, L. Z.; Xu, X. D.; He, H. Y. Charge-mediated co-assembly of amphiphilic peptide and antibiotics into supramolecular hydrogel with antibacterial activity. Front. Bioeng. Biotechnol. 2020, 8, 629452.
Crossref Google Scholar
[21]

Cao, M. W.; Lu, S.; Wang, N. N.; Xu, H.; Cox, H.; Li, R. H.; Waigh, T.; Han, Y. C.; Wang, Y. L.; Lu, J. R. Enzyme-triggered morphological transition of peptide nanostructures for tumor-targeted drug delivery and enhanced cancer therapy. ACS Appl. Mater. Interfaces 2019, 11, 16357–16366.
Crossref Google Scholar
[22]

Ren, C. H.; Gao, Y.; Guan, Y.; Wang, Z. Y.; Yang, L. J.; Gao, J.; Fan, H. R.; Liu, J. F. Carrier-free supramolecular hydrogel composed of dual drugs for conquering drug resistance. ACS Appl. Mater. Interfaces 2019, 11, 33706–33715.
Crossref Google Scholar
[23]

Li, I. C.; Moore, A. N.; Hartgerink, J. D. “Missing tooth” multidomain peptide nanofibers for delivery of small molecule drugs. Biomacromolecules 2016, 17, 2087–2095.
Crossref Google Scholar
[24]

Shi, L.; Kuang, D. Q.; Ma, X. M.; Jalalah, M.; Alsareii, S. A.; Gao, T.; Harraz, F. A.; Yang, J.; Li, G. X. Peptide assembled in a nano-confined space as a molecular rectifier for the availability of ionic current modulation. Nano Lett. 2022, 22, 1083–1090.
Crossref Google Scholar
[25]

Su, Z. Q.; Shen, H. Y.; Wang, H. X.; Wang, J. H.; Li, J. F.; Nienhaus, G. U.; Shang, L.; Wei, G. Motif-designed peptide nanofibers decorated with graphene quantum dots for simultaneous targeting and imaging of tumor cells. Adv. Funct. Mater. 2015, 25, 5472–5478.
Crossref Google Scholar
[26]

Yang, J.; An, H. W.; Wang, H. Self-assembled peptide drug delivery systems. ACS Appl. Bio Mater. 2021, 4, 24–46.
Crossref Google Scholar
[27]

Song, Y. L.; Wang, Y. D.; Wang, S. Y.; Cheng, Y.; Lu, Q. L.; Yang, L. F.; Tan, F. P.; Li, N. Immune-adjuvant loaded Bi2Se3 nanocage for photothermal-improved PD-L1 checkpoint blockade immune-tumor metastasis therapy. Nano Res. 2019, 12, 1770–1780.
Crossref Google Scholar
[28]

Song, Y. Q.; Li, M. M.; Song, N.; Liu, X.; Wu, G. Y.; Zhou, H.; Long, J. F.; Shi, L. Q.; Yu, Z. L. Self-amplifying assembly of peptides in macrophages for enhanced inflammatory treatment. J. Am. Chem. Soc. 2022, 144, 6907–6917.
Crossref Google Scholar
[29]

Pandit, G.; Roy, K.; Agarwal, U.; Chatterjee, S. Self-assembly mechanism of a peptide-based drug delivery vehicle. ACS Omega 2018, 3, 3143–3155.
Crossref Google Scholar
[30]

Zhang, F. J.; Hu, C.; Kong, Q. S.; Luo, R. F.; Wang, Y. B. Peptide-/drug-directed self-assembly of hybrid polyurethane hydrogels for wound healing. ACS Appl. Mater. Interfaces 2019, 11, 37147–37155.
Crossref Google Scholar
[31]

Chen, B.; He, X. Y.; Yi, X. Q.; Zhuo, R. X.; Cheng, S. X. Dual-peptide-functionalized albumin-based nanoparticles with pH-dependent self-assembly behavior for drug delivery. ACS Appl. Mater. Interfaces 2015, 7, 15148–15153.
Crossref Google Scholar
[32]

Shen, F. Y.; Sun, L. L.; Wang, L. H.; Peng, R.; Fan, C. H.; Liu, Z. Framework nucleic acid immune adjuvant for transdermal delivery based chemo-immunotherapy for malignant melanoma treatment. Nano Lett. 2022, 22, 4509–4518.
Crossref Google Scholar
[33]

Liu, Q.; Chen, F. Q.; Hou, L.; Shen, L. M.; Zhang, X. Q.; Wang, D. G.; Huang, L. Nanocarrier-mediated chemo-immunotherapy arrested cancer progression and induced tumor dormancy in desmoplastic melanoma. ACS Nano 2018, 12, 7812–7825.
Crossref Google Scholar
[34]

Hong, X. Y.; Wu, Z. Z.; Chen, L. Z.; Wu, F.; Wei, L. M.; Yuan, W. E. Hydrogel microneedle arrays for transdermal drug delivery. Nano-Micro Lett. 2014, 6, 191–199.
Crossref Google Scholar
[35]

Ramot, Y.; Haim-Zada, M.; Domb, A. J.; Nyska, A. Biocompatibility and safety of PLA and its copolymers. Adv. Drug Delivery Rev. 2016, 107, 153–162.
Crossref Google Scholar
[36]

Demir, Y. K.; Akan, Z.; Kerimoglu, O. Characterization of polymeric microneedle arrays for transdermal drug delivery. PLoS One 2013, 8, e77289.
Crossref Google Scholar
[37]

Larrañeta, E.; Lutton, R. E. M.; Woolfson, A. D.; Donnelly, R. F. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Mater. Sci. Eng. R Rep. 2016, 104, 1–32.
Crossref Google Scholar
[38]

Qu, M. Y.; Kim, H. J.; Zhou, X. W.; Wang, C. R.; Jiang, X.; Zhu, J. X.; Xue, Y. M.; Tebon, P.; Sarabi, S. A.; Ahadian, S. et al. Biodegradable microneedle patch for transdermal gene delivery. Nanoscale 2020, 12, 16724–16729.
Crossref Google Scholar
[39]

Wang, C.; Ye, Y. Q.; Hochu, G. M.; Sadeghifar, H.; Gu, Z. Enhanced cancer immunotherapy by microneedle patch-assisted delivery of anti-PD1 antibody. Nano Lett. 2016, 16, 2334–2340.
Crossref Google Scholar
[40]

Shimizu, T.; Masuda, M.; Minamikawa, H. Supramolecular nanotube architectures based on amphiphilic molecules. Chem. Rev. 2005, 105, 1401–1444.
Crossref Google Scholar
[41]

Tian, Y. W.; Zhang, L. M.; Liu, F. J.; Wang, M. X.; Li, L. Y.; Guo, M. M.; Xu, H. Y.; Yu, Z. Y.; Wang, W. Z. Multi-stage responsive peptide nanosensor: Anchoring EMT and mitochondria with enhanced fluorescence and boosting tumor apoptosis. Biosens. Bioelectron. 2021, 184, 113235.
Crossref Google Scholar
[42]

Wang, Y. H.; Jia, F.; Wang, Z. H.; Qian, Y. X.; Fan, L. Y.; Gong, H.; Luo, A. Q.; Sun, J.; Hu, Z. Y.; Wang, W. Z. Boosting the theranostic effect of liposomal probes toward prominin-1 through optimized dual-site targeting. Anal. Chem. 2019, 91, 7245–7253.
Crossref Google Scholar
[43]

Lin, X.; Lu, X.; Luo, G. S.; Xiang, H. Progress in PD-1/PD-L1 pathway inhibitors: From biomacromolecules to small molecules. Eur. J. Med. Chem. 2020, 186, 111876.
Crossref Google Scholar
[44]

Magnez, R.; Thiroux, B.; Taront, S.; Segaoula, Z.; Quesnel, B.; Thuru, X. PD-1/PD-L1 binding studies using microscale thermophoresis. Sci. Rep. 2017, 7, 17623.
Crossref Google Scholar
[45]

Luo, Z. M.; Sun, W. J.; Fang, J.; Lee, K.; Li, S.; Gu, Z.; Dokmeci, M. R.; Khademhosseini, A. Biodegradable gelatin methacryloyl microneedles for transdermal drug delivery. Adv. Healthc. Mater. 2019, 8, 1801054.
Crossref Google Scholar
[46]

Zhu, J. X.; Zhou, X. W.; Kim, H. J.; Qu, M. Y.; Jiang, X.; Lee, K.; Ren, L.; Wu, Q. Z.; Wang, C. R.; Zhu, X. M. et al. Gelatin methacryloyl microneedle patches for minimally invasive extraction of skin interstitial fluid. Small 2020, 16, 1905910.
Crossref Google Scholar
[47]

Rodell, C. B.; Arlauckas, S. P.; Cuccarese, M. F.; Garris, C. S.; Li, R.; Ahmed, M. S.; Kohler, R. H.; Pittet, M. J.; Weissleder, R. TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy. Nat. Biomed. Eng. 2018, 2, 578–588.
Crossref Google Scholar
Nano Research
Volume 16 Issue 4,
April 2023
Pages 5335-5345
DOI: 10.1007/s12274-022-5236-z
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
Topics:
Nano detectionDevices Targeted drug delivery

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Received: 24 August 2022
Revised: 18 October 2022
Accepted: 23 October 2022
Published: 31 December 2022
© Tsinghua University Press 2022
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