Skip to content
2000
Volume 32, Issue 7
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Peptide nucleic acid (PNA) plays an important role in antimicrobial activity, but its cellular permeability is poor. To overcome this limitation, we constructed biomimetic nanoparticles by using extracellular vesicle (EV)-coated mesoporous silicon nanoparticles (MSNs) to deliver PNA to () and improve its antisense therapeutic effect.

Methods

MSN was prepared by the sol-gel method, and EV was extracted by affinity resin chromatography. EV was coated on MSN by simple sonication (50 W, 3 mins) to prepare biomimetic nanoparticles with PNA-loaded MSN as the core and EV isolated from as the shell.

Results

The MSN prepared by the sol-gel method had a uniform particle size (100 nm) and well-defined pore size for loading PNA with good encapsulation efficiency (62.92%) and drug loading (7.74%). The concentration of EV extracted by affinity resin chromatography was about 1.74 mg/mL. EV could be well coated on MSN through simple ultrasonic treatment (50 W, 3 mins), and the stability and blood compatibility of MSN@EV were good. Internalization experiments showed that EV could selectively enhance the uptake of biomimetic nanoparticles by . Preliminary antibacterial tests revealed that PNA@MSN@EV exhibited enhanced antibacterial activity against and had stronger bactericidal activity than free PNA and PNA@MSN at equivalent PNA concentrations (8 µM).

Conclusion

Biomimetic nanoparticles based on EV-coated MSN offer a new strategy to improve the efficacy of PNA for the treatment of bacterial infections, and the technology holds promise for extension to the delivery of antibiotics that are traditionally minimally effective or prone to resistance.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673266457231123042819
2024-01-20
2025-04-19
Loading full text...

Full text loading...

References

  1. PelfreneE. WillebrandE. Cavaleiro SanchesA. SebrisZ. CavaleriM. Bacteriophage therapy: A regulatory perspective.J. Antimicrob. Chemother.20167182071207410.1093/jac/dkw08327068400
    [Google Scholar]
  2. BebbingtonC. YarrantonG. Antibodies for the treatment of bacterial infections: current experience and future prospects.Curr. Opin. Biotechnol.200819661361910.1016/j.copbio.2008.10.00219000762
    [Google Scholar]
  3. GreberK.E. DawgulM. Antimicrobial peptides under clinical trials.Curr. Top. Med. Chem.201717562062810.2174/156802661666616071314333127411322
    [Google Scholar]
  4. de la Fuente-NunezC. LuT.K. CRISPR-Cas9 technology: Applications in genome engineering, development of sequence-specific antimicrobials, and future prospects.Integrative biology201792109122
    [Google Scholar]
  5. AgrawalS. KandimallaE.R. Antisense therapeutics: Is it as simple as complementary base recognition?Mol. Med. Today200062728110.1016/S1357‑4310(99)01638‑X10652480
    [Google Scholar]
  6. MyersK.J. DeanN.M. Sensible use of antisense: How to use oligonucleotides as research tools.Trends Pharmacol. Sci.2000211192310.1016/S0165‑6147(99)01420‑010637651
    [Google Scholar]
  7. HyrupB. NielsenP.E. Peptide Nucleic Acids (PNA): Synthesis, properties and potential applications.Bioorg. Med. Chem.19964152310.1016/0968‑0896(95)00171‑98689239
    [Google Scholar]
  8. ShakeelS. KarimS. AliA. Peptide nucleic acid (PNA)-a review.J. Chem. Technol. Biotechnol.200681689289910.1002/jctb.1505
    [Google Scholar]
  9. NielsenP.E. Structural and biological properties of peptide nucleic acid (PNA).Pure Appl. Chem.199870110511010.1351/pac199870010105
    [Google Scholar]
  10. DemidovV.V. Frank-KamenetskiiM.D. Two sides of the coin: Affinity and specificity of nucleic acid interactions.Trends Biochem. Sci.2004292627110.1016/j.tibs.2003.12.00715102432
    [Google Scholar]
  11. UhlmannE. PeymanA. BreipohlG. WillD.W. PNA: Synthetic polyamide nucleic acids with unusual binding properties.Angew. Chem. Int. Ed.199837202796282310.1002/(SICI)1521‑3773(19981102)37:20<2796::AID‑ANIE2796>3.0.CO;2‑K29711102
    [Google Scholar]
  12. KoppelhusU. NielsenP.E. Cellular delivery of peptide nucleic acid (PNA).Adv. Drug Deliv. Rev.200355226728010.1016/S0169‑409X(02)00182‑512564980
    [Google Scholar]
  13. NielsenP.E. EgholmM. BuchardtO. Peptide nucleic acid (PNA). A DNA mimic with a peptide backbone.Bioconjug. Chem.1994513710.1021/bc00025a0018199231
    [Google Scholar]
  14. VolpiS. CancelliU. NeriM. CorradiniR. Multifunctional delivery systems for peptide nucleic acids.Pharmaceuticals20201411410.3390/ph1401001433375595
    [Google Scholar]
  15. BarkowskyG. LemsterA.L. PappeschR. JacobA. KrügerS. SchröderA. KreikemeyerB. PatengeN. Influence of different cell-penetrating peptides on the antimicrobial efficiency of PNAs in Streptococcus pyogenes.Mol. Ther. Nucleic Acids20191844445410.1016/j.omtn.2019.09.01031655262
    [Google Scholar]
  16. XueX.Y. MaoX.G. ZhouY. ChenZ. HuY. HouZ. LiM.K. MengJ.R. LuoX.X. Advances in the delivery of antisense oligonucleotides for combating bacterial infectious diseases.Nanomedicine201814374575810.1016/j.nano.2017.12.02629341934
    [Google Scholar]
  17. CastilloR.R. LozanoD. GonzálezB. ManzanoM. Izquierdo-BarbaI. Vallet-RegíM. Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: An update.Expert Opin. Drug Deliv.201916441543910.1080/17425247.2019.159837530897978
    [Google Scholar]
  18. RahikkalaA. PereiraS.A.P. FigueiredoP. PassosM.L.C. AraújoA.R.T.S. SaraivaM.L.M.F.S. SantosH.A. Mesoporous silica nanoparticles for targeted and stimuli responsive delivery of chemotherapeutics: A review.Adv. Biosyst.201827180002010.1002/adbi.201800020
    [Google Scholar]
  19. LiongM. LuJ. TamanoiF. ZinkJ.I. Mesoporous silica nanoparticles for biomedical applications.US10668024B22018https://patents.google.com/patent/US10668024B2/en
  20. YangS. HanX. YangY. QiaoH. YuZ. LiuY. WangJ. TangT. Bacteria-targeting nanoparticles with microenvironment-responsive antibiotic release to eliminate intracellular Staphylococcus aureus and associated infection.ACS Appl. Mater. Interfaces20181017142991431110.1021/acsami.7b1567829633833
    [Google Scholar]
  21. AvitabileC. AccardoA. RinghieriP. MorelliG. SavianoM. MontagnerG. FabbriE. GalleraniE. GambariR. RomanelliA. Incorporation of naked peptide nucleic acids into liposomes leads to fast and efficient delivery.Bioconjug. Chem.20152681533154110.1021/acs.bioconjchem.5b0015626176882
    [Google Scholar]
  22. ZhangB.C. LuoB.Y. ZouJ.J. WuP.Y. JiangJ.L. LeJ.Q. ZhaoR.R. ChenL. ShaoJ.W. Co-delivery of Sorafenib and CRISPR/Cas9 based on targeted core–shell hollow mesoporous organosilica nanoparticles for synergistic HCC therapy.ACS Appl. Mater. Interfaces20201251573625737210.1021/acsami.0c1766033301289
    [Google Scholar]
  23. NiuJ. TangG. TangJ. YangJ. ZhouZ. GaoY. ChenX. TianY. LiY. LiJ. CaoY. Functionalized silver nanocapsules with improved antibacterial activity using silica shells modified with quaternary ammonium polyethyleneimine as a bacterial cell-targeting agent.J. Agric. Food Chem.202169236485649410.1021/acs.jafc.1c0193034077226
    [Google Scholar]
  24. LuF. ZhanC. GongY. TangY. XieC. WangQ. WangW. FanQ. HuangW. A general strategy to encapsulate semiconducting polymers within pegylated mesoporous silica nanoparticles for optical imaging and drug delivery.Part. Syst. Char.20203761900483
    [Google Scholar]
  25. KellyI.B.III FletcherR.B. McBrideJ.R. WeissS.M. DuvallC.L. Tuning composition of polymer and porous silicon composite nanoparticles for early endosome escape of anti-microRNA peptide nucleic acids.ACS Appl. Mater. Interfaces20201235396023961110.1021/acsami.0c0582732805967
    [Google Scholar]
  26. KhatamiF. MatinM.M. DaneshN.M. BahramiA.R. AbnousK. TaghdisiS.M. Targeted delivery system using silica nanoparticles coated with chitosan and AS1411 for combination therapy of doxorubicin and antimiR-21.Carbohydr. Polym.202126611811110.1016/j.carbpol.2021.11811134044928
    [Google Scholar]
  27. YanL.X. WangB.B. ZhaoX. ChenL.J. YanX.P. A pH-responsive persistent luminescence nanozyme for selective imaging and killing of Helicobacter pylori and common resistant bacteria.ACS Appl. Mater. Interfaces20211351609556096510.1021/acsami.1c2131834904434
    [Google Scholar]
  28. SudagidanM. YildizG. OnenS. AlR. TemizŞ.N. YurtM.N.Z. TasbasiB.B. AcarE.E. CobanA. AydinA. DursunA.D. OzalpV.C. Targeted mesoporous silica nanoparticles for improved inhibition of disinfectant resistant Listeria monocytogenes and lower environmental pollution.J. Hazard. Mater.202141812636410.1016/j.jhazmat.2021.12636434329020
    [Google Scholar]
  29. ZhuangJ. ChenS. HuY. YangF. HuoQ. XieN. Tumour-targeted and redox-responsive mesoporous silica nanoparticles for controlled release of doxorubicin and an siRNA against metastatic breast cancer.Int. J. Nanomedicine2021161961197610.2147/IJN.S27872433727809
    [Google Scholar]
  30. ChenC. YaoW. SunW. GuoT. LvH. WangX. YingH. WangY. WangP. A self-targeting and controllable drug delivery system constituting mesoporous silica nanoparticles fabricated with a multi-stimuli responsive chitosan-based thin film layer.Int. J. Biol. Macromol.20191221090109910.1016/j.ijbiomac.2018.09.05830219514
    [Google Scholar]
  31. LinJ.T. YeQ.B. YangQ.J. WangG.H. Hierarchical bioresponsive nanocarriers for codelivery of curcumin and doxorubicin.Colloids Surf. B Biointerfaces20191809310110.1016/j.colsurfb.2019.04.02331035057
    [Google Scholar]
  32. O’BrienK. BreyneK. UghettoS. LaurentL.C. BreakefieldX.O. RNA delivery by extracellular vesicles in mammalian cells and its applications.Nat. Rev. Mol. Cell Biol.2020211058560610.1038/s41580‑020‑0251‑y32457507
    [Google Scholar]
  33. HerrmannI.K. WoodM.J.A. FuhrmannG. Extracellular vesicles as a next-generation drug delivery platform.Nat. Nanotechnol.202116774875910.1038/s41565‑021‑00931‑234211166
    [Google Scholar]
  34. BrownL. WolfJ.M. Prados-RosalesR. CasadevallA. Through the wall: Extracellular vesicles in gram-positive bacteria, mycobacteria and fungi.Nat. Rev. Microbiol.2015131062063010.1038/nrmicro348026324094
    [Google Scholar]
  35. GanY. LiC. PengX. WuS. LiY. TanJ.P.K. YangY.Y. YuanP. DingX. Fight bacteria with bacteria: Bacterial membrane vesicles as vaccines and delivery nanocarriers against bacterial infections.Nanomedicine20213510239810.1016/j.nano.2021.10239833901646
    [Google Scholar]
  36. AngsantikulP. ThamphiwatanaS. GaoW. ZhangL. Cell membrane-coated nanoparticles as an emerging antibacterial vaccine platform.Vaccines20153481482810.3390/vaccines304081426457720
    [Google Scholar]
  37. PagetM.S.B. HelmannJ.D. The sigma70 family of sigma factors.Genome Biol.20034120310.1186/gb‑2003‑4‑1‑20312540296
    [Google Scholar]
  38. ChenW. MaM. LaiQ. ZhangY. LiuZ. DPP-Cu2+ complexes gated mesoporous silica nanoparticles for pH and redox dual stimuli-responsive drug delivery.Curr. Med. Chem.202330283249326010.2174/0929867329666221011110504
    [Google Scholar]
  39. WuS. HuangY. YanJ. LiY. WangJ. YangY.Y. YuanP. DingX. Bacterial outer membrane coated mesoporous silica nanoparticles for targeted delivery of antibiotic Rifampicin against gram-negative bacterial infection in vivo.Adv. Funct. Mater.20213135210344210.1002/adfm.202103442
    [Google Scholar]
  40. RoggersR.A. LinV.S.Y. TrewynB.G. Chemically reducible lipid bilayer coated mesoporous silica nanoparticles demonstrating controlled release and HeLa and normal mouse liver cell biocompatibility and cellular internalization.Mol. Pharm.2012992770277710.1021/mp200613y22738645
    [Google Scholar]
  41. QiuZ. ShuJ. TangD. Bioresponsive release system for visual fluorescence detection of carcinoembryonic antigen from mesoporous silica nanocontainers mediated optical color on quantum dot-enzyme-impregnated paper.Anal. Chem.20178995152516010.1021/acs.analchem.7b0098928376620
    [Google Scholar]
  42. RenS. YangJ. MaL. LiX. WuW. LiuC. HeJ. MiaoL. Ternary-responsive drug delivery with activatable dual mode contrast-enhanced in vivo imaging.ACS Appl. Mater. Interfaces20181038319473195810.1021/acsami.8b1056430179443
    [Google Scholar]
  43. ChenX. SunH. HuJ. HanX. LiuH. HuY. Transferrin gated mesoporous silica nanoparticles for redox-responsive and targeted drug delivery.Colloids Surf. B Biointerfaces2017152778410.1016/j.colsurfb.2017.01.01028088015
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673266457231123042819
Loading
/content/journals/cmc/10.2174/0109298673266457231123042819
Loading

Data & Media loading...

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