Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Drug Delivery
  4. Volume 22, Issue 4
  5. Article
Volume 22, Issue 4
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Because of low immunogenicity, ease of modification, and inherent biosafety, peptides have been well recognized as vehicles to deliver therapeutic agents to targeted regions with improved pharmacokinetic characteristics. Enzyme-responsive self-assembled peptides (ERSAPs) show superiority over their naive forms due to their enhanced targeting efficacy and long-retention property. In this review, we have summarized recent advances in the therapeutic application of ERSAPs, mainly focusing on their self-therapeutic properties and potential as vehicles to deliver different drugs.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdd/10.2174/1567201820666230726151607
2023-07-26
2025-05-05

  • From This Site

    /content/journals/cdd/10.2174/1567201820666230726151607
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AmabilinoD.B. GaleP.A. Supramolecular chemistry anniversary.Chem. Soc. Rev.20174692376237710.1039/C7CS90037F 28443886
     [Google Scholar]
  2. BoekhovenJ. BrizardA.M. KowlgiK.N.K. KoperG.J.M. EelkemaR. van EschJ.H. Dissipative self-assembly of a molecular gelator by using a chemical fuel.Angew. Chem. Int. Ed.201049284825482810.1002/anie.201001511 20512834
     [Google Scholar]
  3. ChenJ. ZhaoY. YaoQ. GaoY. Pathological environment directed in situ peptidic supramolecular assemblies for nanomedicines.Biomed. Mater.202116202201110.1088/1748‑605X/abc2e9 33630754
     [Google Scholar]
  4. GuptaS. SinghI. SharmaA.K. KumarP. Ultrashort peptide self-assembly: Front-runners to transport drug and gene cargos.Front. Bioeng. Biotechnol.2020850410.3389/fbioe.2020.00504 32548101
     [Google Scholar]
  5. BrownN. LeiJ. ZhanC. ShimonL.J.W. Adler-AbramovichL. WeiG. GazitE. Structural polymorphism in a self-assembled tri-aromatic peptide system.ACS Nano20181243253326210.1021/acsnano.7b07723 29558116
     [Google Scholar]
  6. WangQ. XiaoM. WangD. HouX. GaoJ. LiuJ. LiuJ. In situ supramolecular self‐assembly of Pt(IV) prodrug to conquer cisplatin resistance.Adv. Funct. Mater.20213127210182610.1002/adfm.202101826
     [Google Scholar]
  7. GongZ. ZhouB. LiuX. CaoJ. HongZ. WangJ. SunX. YuanX. TanH. JiH. BaiJ. Enzyme-induced transformable peptide nanocarriers with enhanced drug permeability and retention to improve tumor nanotherapy efficacy.ACS Appl. Mater. Interfaces20211347559135592710.1021/acsami.1c17917 34784165
     [Google Scholar]
  8. OakesS.A. PapaF.R. The role of endoplasmic reticulum stress in human pathology.Annu. Rev. Pathol.201510117319410.1146/annurev‑pathol‑012513‑104649 25387057
     [Google Scholar]
  9. PentlavalliS. CoulterS. LavertyG. Peptide nanomaterials for drug delivery applications.Curr. Protein Pept. Sci.202021440141210.2174/1389203721666200101091834 31893991
     [Google Scholar]
  10. GurevichL. PoulsenT.W. AndersenO.Z. KildebyN.L. FojanP. PH-dependent self-assembly of the short Surfactant-like peptide KA6.J. Nanosci. Nanotechnol.201010127946795010.1166/jnn.2010.2667 21121281
     [Google Scholar]
  11. ZhouP. HuX. LiJ. WangY. YuH. ChenZ. WangD. ZhaoY. KingS.M. RogersS.E. WangJ. LuJ.R. XuH. Peptide self-assemblies from unusual α-sheet conformations based on alternation of D/L amino acids.J. Am. Chem. Soc.202214447215442155410.1021/jacs.2c08425 36345816
     [Google Scholar]
  12. ZhouJ. DuX. ChenX. WangJ. ZhouN. WuD. XuB. Enzymatic self-assembly confers exceptionally strong synergism with NF-κB targeting for selective necroptosis of cancer cells.J. Am. Chem. Soc.201814062301230810.1021/jacs.7b12368 29377688
     [Google Scholar]
  13. MacPhersonD.S. McPheeS.A. ZeglisB.M. UlijnR.V. The impact of tyrosine iodination on the aggregation and cleavage kinetics of MMP-9-responsive peptide sequences.ACS Biomater. Sci. Eng.20228257958710.1021/acsbiomaterials.1c01488 35050574
     [Google Scholar]
  14. HuangR.H. NayeemN. HeY. MoralesJ. GrahamD. KlajnR. ContelM. O’BrienS. UlijnR.V. Self‐complementary zwitterionic peptides direct nanoparticle assembly and enable enzymatic selection of endocytic pathways.Adv. Mater.2022341210496210.1002/adma.202104962 34668253
     [Google Scholar]
  15. SongY. LiM. SongN. LiuX. WuG. ZhouH. LongJ. ShiL. YuZ. Self-amplifying assembly of peptides in macrophages for enhanced inflammatory treatment.J. Am. Chem. Soc.2022144156907691710.1021/jacs.2c01323 35388694
     [Google Scholar]
  16. ZhanJ. CaiY. HeS. WangL. YangZ. Tandem molecular self-assembly in liver cancer cells.Angew. Chem. Int. Ed.20185771813181610.1002/anie.201710237 29276818
     [Google Scholar]
  17. ZhouJ. DuX. YamagataN. XuB. Enzyme-instructed self-assembly of small D -peptides as a multiple-step process for selectively killing cancer cells.J. Am. Chem. Soc.2016138113813382310.1021/jacs.5b13541 26966844
     [Google Scholar]
  18. CongY. JiL. GaoY.J. LiuF.H. ChengD.B. HuZ. QiaoZ.Y. WangH. Microenvironment‐induced in situ self‐assembly of polymer–peptide conjugates that attack solid tumors deeply.Angew. Chem. Int. Ed.201958144632463710.1002/anie.201900135 30695128
     [Google Scholar]
  19. TaoM. HeS. LiuJ. LiH. MeiL. WuC. XuK. ZhongW. The conjugates of forky peptides and nonsteroidal anti-inflammatory drugs (NSAID) self-assemble into supramolecular hydrogels for prostate cancer-specific drug delivery.J. Mater. Chem. B Mater. Biol. Med.20197346947610.1039/C8TB02307G 32254734
     [Google Scholar]
  20. ChengD.B. ZhangX.H. ChenY. ChenH. QiaoZ.Y. WangH. Ultrasound-Activated Cascade Effect for Synergistic Orthotopic Pancreatic Cancer Therapy.Science202023610114410.1016/j.isci.2020.101144 32446222
     [Google Scholar]
  21. DaiY. XuC. SunX. ChenX. Nanoparticle design strategies for enhanced anticancer therapy by exploiting the tumour microenvironment.Chem. Soc. Rev.201746123830385210.1039/C6CS00592F 28516983
     [Google Scholar]
  22. WangY.F. ZhangC. YangK. WangY. ShanS. YanY. DawsonK.A. WangC. LiangX.J. Transportation of AIE-visualized nanoliposomes is dominated by the protein corona.Natl. Sci. Rev.202186nwab06810.1093/nsr/nwab068 34691676
     [Google Scholar]
  23. ZhouQ. DongC. FanW. JiangH. XiangJ. QiuN. PiaoY. XieT. LuoY. LiZ. LiuF. ShenY. Tumor extravasation and infiltration as barriers of nanomedicine for high efficacy: The current status and transcytosis strategy.Biomaterials202024011990210.1016/j.biomaterials.2020.119902
     [Google Scholar]
  24. Challenging paradigms in tumour drug delivery.Nat. Mater.202019547710.1038/s41563‑020‑0676‑x 32332992
     [Google Scholar]
  25. Meyer-SabellekW. SinhaP. KöttgenE. Alkaline phosphatase. Laboratory and clinical implications.J. Chromatogr. A1988429419444
     [Google Scholar]
  26. NiuX. YeK. WangL. LinY. DuD. A review on emerging principles and strategies for colorimetric and fluorescent detection of alkaline phosphatase activity.Anal. Chim. Acta20191086294510.1016/j.aca.2019.07.068 31561792
     [Google Scholar]
  27. EgebladM. WerbZ. New functions for the matrix metalloproteinases in cancer progression.Nat. Rev. Cancer20022316117410.1038/nrc745 11990853
     [Google Scholar]
  28. AlaseemA. AlhazzaniK. DondapatiP. AlobidS. BishayeeA. RathinaveluA. Matrix Metalloproteinases: A challenging paradigm of cancer management.Semin. Cancer Biol.20195610011510.1016/j.semcancer.2017.11.008
     [Google Scholar]
  29. BarghJ.D. Isidro-LlobetA. ParkerJ.S. SpringD.R. Cleavable linkers in antibody–drug conjugates.Chem. Soc. Rev.201948164361437410.1039/C8CS00676H 31294429
     [Google Scholar]
  30. MijanovićO. BrankovićA. PaninA.N. SavchukS. TimashevP. UlasovI. LesniakM.S. Cathepsin B: A sellsword of cancer progression.Cancer Lett.201944920721410.1016/j.canlet.2019.02.035
     [Google Scholar]
  31. WangZ. YangC. ZhangH. GaoY. XiaoM. WangZ. YangL. ZhangJ. RenC. LiuJ. In situ transformable supramolecular nanomedicine targeted activating hippo pathway for triple-negative breast cancer growth and metastasis inhibition.ACS Nano2022169146441465710.1021/acsnano.2c05263 36048539
     [Google Scholar]
  32. DuX. ZhouJ. WangH. ShiJ. KuangY. ZengW. YangZ. XuB. In situ generated D‐peptidic nanofibrils as multifaceted apoptotic inducers to target cancer cells.Cell Death Dis.201782e2614e261410.1038/cddis.2016.466 28206986
     [Google Scholar]
  33. TanakaA. FukuokaY. MorimotoY. HonjoT. KodaD. GotoM. MaruyamaT. Cancer cell death induced by the intracellular self-assembly of an enzyme-responsive supramolecular gelator.J. Am. Chem. Soc.2015137277077510.1021/ja510156v 25521540
     [Google Scholar]
  34. PengX. HaoJ. TaoW. GuoD. LiangT. HuX. XuH. FanX. ChenC. Amyloid-like aggregates of short self-assembly peptide selectively induce melanoma cell apoptosis.J. Colloid Interface Sci.202364049850910.1016/j.jcis.2023.02.088 36871514
     [Google Scholar]
  35. ChengX. XiaT. ZhanW. XuH.D. JiangJ. LiuX. SunX. WuF.G. LiangG. Enzymatic nanosphere‐to‐nanofiber transition and autophagy inducer release promote tumor chemotherapy.Adv. Healthc. Mater.20221123220191610.1002/adhm.202201916 36148589
     [Google Scholar]
  36. XuT. CaiY. ZhongX. β-Galactosidase-directed supramolecular hydrogels for selective identification and removal of senescent cells.Chem. Commun.201955507175717810.1039/C9CC03056E 31162503
     [Google Scholar]
  37. MoritaK. NishimuraK. YamamotoS. ShimizuN. YashiroT. KawabataR. AoiT. TamuraA. MaruyamaT. In situ synthesis of an anticancer peptide amphiphile using tyrosine kinase overexpressed in cancer cells.JACS Au2022292023202810.1021/jacsau.2c00301
     [Google Scholar]
  38. SunM. WangC. LvM. FanZ. DuJ. Intracellular self-assembly of peptides to induce apoptosis against drug-resistant melanoma.J. Am. Chem. Soc.2022144167337734510.1021/jacs.2c00697 35357824
     [Google Scholar]
  39. ChengY. ClarkA.E. ZhouJ. HeT. LiY. BorumR.M. CreyerM.N. XuM. JinZ. ZhouJ. YimW. WuZ. FajtováP. O’DonoghueA.J. CarlinA.F. JokerstJ.V. Protease-responsive peptide-conjugated mitochondrial-targeting AIEgens for selective imaging and inhibition of SARS-CoV-2-infected cells.ACS Nano2022168123051231710.1021/acsnano.2c03219 35878004
     [Google Scholar]
  40. ZhangX.Y. LiuC. FanP.S. ZhangX.H. HouD.Y. WangJ.Q. YangH. WangH. QiaoZ.Y. Skin-like wound dressings with on-demand administration based on in situ peptide self-assembly for skin regeneration.J. Mater. Chem. B Mater. Biol. Med.202210193624363610.1039/D2TB00348A 35420616
     [Google Scholar]
  41. GuoR.C. ZhangX.H. FanP.S. SongB.L. LiZ.X. DuanZ.Y. QiaoZ.Y. WangH. In vivo self‐assembly induced cell membrane phase separation for improved peptide drug internalization.Angew. Chem. Int. Ed.20216047251282513410.1002/anie.202111839 34549872
     [Google Scholar]
  42. MossalamM. DixonA.S. LimC.S. Controlling subcellular delivery to optimize therapeutic effect.Ther. Deliv.20101116919310.4155/tde.10.8 21113240
     [Google Scholar]
  43. JavadpourM.M. JubanM.M. LoW.C. BishopS.M. AlbertyJ.B. CowellS.M. BeckerC.L. McLaughlinM.L. New antimicrobial peptides with low mammalian cytotoxicity.J. Med. Chem.199639163107311310.1021/jm9509410 8759631
     [Google Scholar]
  44. WangH. FengZ. WuD. FritzschingK.J. RigneyM. ZhouJ. JiangY. Schmidt-RohrK. XuB. Enzyme-regulated supramolecular assemblies of cholesterol conjugates against drug-resistant ovarian cancer cells.J. Am. Chem. Soc.201613834107581076110.1021/jacs.6b06075 27529637
     [Google Scholar]
  45. JiangZ. GuanJ. QianJ. ZhanC. Peptide ligand-mediated targeted drug delivery of nanomedicines.Biomater. Sci.20197246147110.1039/C8BM01340C 30656305
     [Google Scholar]
  46. AnH. MamutiM. WangX. Rationally designed modular drug delivery platform based on intracellular peptide self-assembly.Exploration202112
     [Google Scholar]
  47. LiuN. ZhuL. LiZ. LiuW. SunM. ZhouZ. In situ self-assembled peptide nanofibers for cancer theranostics.Biomater. Sci.20219165427543610.1039/D1BM00782C 34319316
     [Google Scholar]
  48. HuY. WangY. DengJ. DingX. LinD. ShiH. ChenL. LinD. WangY. VakalS. WangJ. LiX. Enzyme-instructed self-assembly of peptide-drug conjugates in tear fluids for ocular drug delivery.J. Control. Release202234426127110.1016/j.jconrel.2022.03.011
     [Google Scholar]
  49. WangD. ChengD-B. JiL. NiuL-J. ZhangX-H. CongY. CaoR-H. ZhouL. BaiF. QiaoZ-Y. WangH. Precise magnetic resonance imaging-guided sonodynamic therapy for drug-resistant bacterial deep infection.Biomaterials202126412038610.1016/j.biomaterials.2020.120386
     [Google Scholar]
  50. TangW. ZhaoZ. ChongY. WuC. LiuQ. YangJ. ZhouR. LianZ.X. LiangG. Tandem enzymatic self-assembly and slow release of dexamethasone enhances its antihepatic fibrosis effect.ACS Nano201812109966997310.1021/acsnano.8b04143 30285414
     [Google Scholar]
  51. ChenY. WangQ. LiZ. LiuZ. ZhaoY. ZhangJ. LiuM. WangZ. LiD. HanJ. Naproxen platinum(IV) hybrids inhibiting cycloxygenases and matrix metalloproteinases and causing DNA damage: Synthesis and biological evaluation as antitumor agents in vitro and in vivo.Dalton Trans.202049165192520410.1039/D0DT00424C 32236281
     [Google Scholar]
  52. ChengD.B. ZhangX.H. GaoY.J. WangD. WangL. ChenH. QiaoZ.Y. WangH. Site‐specific construction of long‐term drug depot for suppression of tumor recurrence.Small20191539190181310.1002/smll.201901813 31389136
     [Google Scholar]
  53. CaoM. LuS. WangN. XuH. CoxH. LiR. WaighT. HanY. WangY. LuJ.R. Enzyme-triggered morphological transition of peptide nanostructures for tumor-targeted drug delivery and enhanced cancer therapy.ACS Appl. Mater. Interfaces20191118163571636610.1021/acsami.9b03519 30991000
     [Google Scholar]
  54. DolcetX. LlobetD. PallaresJ. Matias-GuiuX. NF-kB in development and progression of human cancer.Virchows Arch.2005446547548210.1007/s00428‑005‑1264‑9 15856292
     [Google Scholar]
  55. MélinL. AbdullayevS. FnaicheA. VuV. González SuárezN. ZengH. SzewczykM.M. LiF. SenisterraG. Allali-HassaniA. ChauI. DongA. WooS. AnnabiB. HalabelianL. LaPlanteS.R. VedadiM. Barsyte-LovejoyD. SanthakumarV. GagnonA. Development of LM98, a small-molecule TEAD inhibitor derived from flufenamic acid.ChemMedChem202116192982300210.1002/cmdc.202100432 34164919
     [Google Scholar]
  56. XuQ. LuR. ZhuZ.F. LvJ.Q. WangL.J. ZhangW. HuJ.W. MengJ. LinG. YaoZ. Effects of tyroservatide on histone acetylation in lung carcinoma cells.Int. J. Cancer2011128246047210.1002/ijc.25346 20309941
     [Google Scholar]
  57. AwwadS. Mohamed AhmedA.H.A. SharmaG. HengJ.S. KhawP.T. BrocchiniS. LockwoodA. Principles of pharmacology in the eye.Br. J. Pharmacol.2017174234205422310.1111/bph.14024 28865239
     [Google Scholar]
  58. ZhengD. LiuJ. XieL. WangY. DingY. PengR. CuiM. WangL. ZhangY. ZhangC. YangZ. Enzyme-instructed and mitochondria-targeting peptide self-assembly to efficiently induce immunogenic cell death.Acta Pharm. Sin. B20221262740275010.1016/j.apsb.2021.07.005 35755291
     [Google Scholar]
  59. GaoY. ZhangC. ChangJ. YangC. LiuJ. FanS. RenC. Enzyme-instructed self-assembly of a novel histone deacetylase inhibitor with enhanced selectivity and anticancer efficiency.Biomater. Sci.2019741477148510.1039/C8BM01422A 30672520
     [Google Scholar]
  60. LiX. WangY. ZhangY. YangZ. GaoJ. ShiY. Enzyme-instructed self-assembly (EISA) assists the self-assembly and hydrogelation of hydrophobic peptides.J. Mater. Chem. B Mater. Biol. Med.202210173242324710.1039/D2TB00182A 35437539
     [Google Scholar]
  61. YamamuraK. KibbeyM.C. JunS.H. KleinmanH.K. Effect of Matrigel and laminin peptide YIGSR on tumor growth and metastasis.Semin. Cancer Biol.199344259265 8400148
     [Google Scholar]
  62. LvM-Y. XiaoW-Y. ZhangY-P. JinL-L. LiZ-H. LeiZ. ChengD-B. JinS-D. In situ self-assembled peptide enables effective cancer immunotherapy by blockage of CD47.Colloids Surf. B Biointerfaces202221711265510.1016/j.colsurfb.2022.112655
     [Google Scholar]
  63. ChenB. DongX. DongX. WangQ. WuM. WuJ. LouX. XiaF. WangW. DaiJ. WangS. Integration of dual targeting and dual therapeutic modules endows self-assembled nanoparticles with anti-tumor growth and metastasis functions.Int. J. Nanomedicine2021161361137610.2147/IJN.S291285 33658777
     [Google Scholar]
  64. ZhangD. QiG.B. ZhaoY.X. QiaoS.L. YangC. WangH. In Situ Formation of nanofibers from purpurin18-peptide conjugates and the assembly induced retention effect in tumor sites.Adv. Mater.201527406125613010.1002/adma.201502598 26350172
     [Google Scholar]
  65. LiJ. XiaoS. XuY. ZuoS. ZhaZ. KeW. HeC. GeZ. Smart asymmetric vesicles with triggered availability of inner cell-penetrating shells for specific intracellular drug delivery.ACS Appl. Mater. Interfaces2017921177271773510.1021/acsami.7b02808 28489341
     [Google Scholar]
  66. HeH. GuoJ. XuJ. WangJ. LiuS. XuB. Dynamic continuum of nanoscale peptide assemblies facilitates endocytosis and endosomal escape.Nano Lett.20212194078408510.1021/acs.nanolett.1c01029 33939437
     [Google Scholar]
  67. ZhuJ.Q. WuH. LiZ.L. XuX.F. XingH. WangM.D. JiaH.D. LiangL. LiC. SunL.Y. WangY.G. ShenF. HuangD.S. YangT. Responsive hydrogels based on triggered click reactions for liver cancer.Adv. Mater.20223438220165110.1002/adma.202201651 35583434
     [Google Scholar]
  68. WangY. HuQ. Bio-orthogonal chemistry in cell engineering.Adv. NanoBiomed Res.2022332200128 https://onlinelibrary.wiley. com/doi/full/10.1002/anbr.202200128.
     [Google Scholar]
  69. PalvaiS. MoodyC.T. PanditS. BrudnoY. On-demand drug release from click-refillable drug depots.Mol. Pharm.202118103920392510.1021/acs.molpharmaceut.1c00535 34494844
     [Google Scholar]
  70. MouY. ZhangP. LaiW.F. ZhangD. Design and applications of liposome-in-gel as carriers for cancer therapy.Drug Deliv.20222913245325510.1080/10717544.2022.2139021 36310364
     [Google Scholar]
  71. LiH. CornelE.J. FanZ. DuJ. Chirality-controlled polymerization-induced self-assembly.Chem. Sci.20221347141791419010.1039/D2SC05695J
     [Google Scholar]
  72. ZerzeG.H. StillingerF.H. DebenedettiP.G. Effect of heterochiral inversions on the structure of a β‐hairpin peptide.Proteins201987756957810.1002/prot.25680 30811673
     [Google Scholar]
  73. NguyenA. ChaoP-H. OngC.Y. RouhollahiE. FayezN.A.L. LinL. BrownJ.I. BöttgerR. PageB. WongH. LiS-D. Chemically engineering the drug release rate of a PEG-paclitaxel conjugate using click and steric hindrance chemistries for optimal efficacy.Biomaterials202228912173510.1016/j.biomaterials.2022.121735
     [Google Scholar]
  74. TaiariolL. ChaixC. FarreC. MoreauE. Click and bioorthogonal chemistry: The future of active targeting of nanoparticles for nanomedicines?Chem. Rev.2022122134038410.1021/acs.chemrev.1c00484 34705429
     [Google Scholar]
/content/journals/cdd/10.2174/1567201820666230726151607
Loading
Advances in Enzyme-responsive Supramolecular In situ Self-assembled Peptide for Drug Delivery
Curr. Drug Deliv. 22, 374 (2025); https://doi.org/10.2174/1567201820666230726151607
/content/journals/cdd/10.2174/1567201820666230726151607
/content/journals/cdd/10.2174/1567201820666230726151607
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): drug delivery; enzyme-responsive; ERSAP; in situ self-assembly; Peptides; supramolecular

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test