Non-Invasive Delivery of Therapeutics into the Brain: The Potential of Aptamers for Targeted Delivery

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2020 May 20

PMID 32422973

Citations 13

Authors

Bakhtiar Bukari

Rasika M Samarasinghe

Jinjutha Noibanchong

Sarah L Shigdar

Affiliations

Soon will be listed here.

Abstract

The blood-brain barrier (BBB) is a highly specialised network of blood vessels that effectively separates the brain environment from the circulatory system. While there are benefits, in terms of keeping pathogens from entering the brain, the BBB also complicates treatments of brain pathologies by preventing efficient delivery of macromolecular drugs to diseased brain tissue. Although current non-invasive strategies of therapeutics delivery into the brain, such as focused ultrasound and nanoparticle-mediated delivery have shown various levels of successes, they still come with risks and limitations. This review discusses the current approaches of therapeutic delivery into the brain, with a specific focus on non-invasive methods. It also discusses the potential for aptamers as alternative delivery systems and several reported aptamers with promising preliminary results.

Citing Articles

Aptamer based immunotherapy: a potential solid tumor therapeutic.

Mathavan S, Tam Y, Mustaffa K, Tye G Front Immunol. 2025; 16:1536569.

PMID: 40034705 PMC: 11873091. DOI: 10.3389/fimmu.2025.1536569.

Targeting Brain Drug Delivery with Macromolecules Through Receptor-Mediated Transcytosis.

Li Y, Liu R, Zhao Z Pharmaceutics. 2025; 17(1).

PMID: 39861756 PMC: 11769103. DOI: 10.3390/pharmaceutics17010109.

A comprehensive review of advanced focused ultrasound (FUS) microbubbles-mediated treatment of Alzheimer's disease.

Rouhi N, Chakeri Z, Ghorbani Nejad B, Rahimzadegan M, Khezri M, Kamali H Heliyon. 2024; 10(18):e37533.

PMID: 39309880 PMC: 11416559. DOI: 10.1016/j.heliyon.2024.e37533.

A Universal Aptamer for Influenza A Viruses: Selection, Recognition, and Infection Inhibition.

Wang M, Hao M, Huangfu Y, Yang K, Zhang X, Zhang Y ACS Pharmacol Transl Sci. 2024; 7(1):249-258.

PMID: 38230279 PMC: 10789145. DOI: 10.1021/acsptsci.3c00258.

The Other Side of Plastics: Bioplastic-Based Nanoparticles for Drug Delivery Systems in the Brain.

Lamparelli E, Marino M, Szychlinska M, Rocca N, Ciardulli M, Scala P Pharmaceutics. 2023; 15(11).

PMID: 38004530 PMC: 10674524. DOI: 10.3390/pharmaceutics15112549.

References

Neyns B, Sadones J, Joosens E, Bouttens F, Verbeke L, Baurain J . Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol. 2009; 20(9):1596-1603. DOI: 10.1093/annonc/mdp032. View

Pujals S, Giralt E . Proline-rich, amphipathic cell-penetrating peptides. Adv Drug Deliv Rev. 2008; 60(4-5):473-84. DOI: 10.1016/j.addr.2007.09.012. View

Lajoie J, Shusta E . Targeting receptor-mediated transport for delivery of biologics across the blood-brain barrier. Annu Rev Pharmacol Toxicol. 2014; 55:613-31. PMC: 5051266. DOI: 10.1146/annurev-pharmtox-010814-124852. View

Park K . Transport across the blood-brain barrier using albumin nanoparticles. J Control Release. 2009; 137(1):1. DOI: 10.1016/j.jconrel.2009.05.004. View

Papademetriou I, Porter T . Promising approaches to circumvent the blood-brain barrier: progress, pitfalls and clinical prospects in brain cancer. Ther Deliv. 2015; 6(8):989-1016. PMC: 4618388. DOI: 10.4155/tde.15.48. View

Zhou G, Latchoumanin O, Hebbard L, Duan W, Liddle C, George J . Aptamers as targeting ligands and therapeutic molecules for overcoming drug resistance in cancers. Adv Drug Deliv Rev. 2018; 134:107-121. DOI: 10.1016/j.addr.2018.04.005. View

Drucker D . Never Waste a Good Crisis: Confronting Reproducibility in Translational Research. Cell Metab. 2016; 24(3):348-360. DOI: 10.1016/j.cmet.2016.08.006. View

Kobus T, Vykhodtseva N, Pilatou M, Zhang Y, McDannold N . Safety Validation of Repeated Blood-Brain Barrier Disruption Using Focused Ultrasound. Ultrasound Med Biol. 2015; 42(2):481-92. PMC: 4816071. DOI: 10.1016/j.ultrasmedbio.2015.10.009. View

Stoltenburg R, Reinemann C, Strehlitz B . SELEX--a (r)evolutionary method to generate high-affinity nucleic acid ligands. Biomol Eng. 2007; 24(4):381-403. DOI: 10.1016/j.bioeng.2007.06.001. View

10.

Eremeeva E, Fikatas A, Margamuljana L, Abramov M, Schols D, Groaz E . Highly stable hexitol based XNA aptamers targeting the vascular endothelial growth factor. Nucleic Acids Res. 2019; 47(10):4927-4939. PMC: 6547419. DOI: 10.1093/nar/gkz252. View

11.

Chen C, Dellamaggiore K, Ouellette C, Sedano C, Lizadjohry M, Chernis G . Aptamer-based endocytosis of a lysosomal enzyme. Proc Natl Acad Sci U S A. 2008; 105(41):15908-13. PMC: 2572987. DOI: 10.1073/pnas.0808360105. View

12.

Shigdar S, Lin J, Yu Y, Pastuovic M, Wei M, Duan W . RNA aptamer against a cancer stem cell marker epithelial cell adhesion molecule. Cancer Sci. 2011; 102(5):991-8. DOI: 10.1111/j.1349-7006.2011.01897.x. View

13.

Chen K, Wei V, Yen L, Poon K, Liu Y, Cheng K . Intravenous mannitol does not increase blood-brain barrier permeability to inert dyes in the adult rat forebrain. Neuroreport. 2013; 24(6):303-7. DOI: 10.1097/WNR.0b013e32835f8acb. View

14.

Robertson D, Joyce G . Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA. Nature. 1990; 344(6265):467-8. DOI: 10.1038/344467a0. View

15.

Porciani D, Signore G, Marchetti L, Mereghetti P, Nifosi R, Beltram F . Two interconvertible folds modulate the activity of a DNA aptamer against transferrin receptor. Mol Ther Nucleic Acids. 2014; 3:e144. PMC: 3912326. DOI: 10.1038/mtna.2013.71. View

16.

Lollo B, Steele F, Gold L . Beyond antibodies: new affinity reagents to unlock the proteome. Proteomics. 2014; 14(6):638-44. DOI: 10.1002/pmic.201300187. View

17.

Sampson J, Archer G, Pedain C, Wembacher-Schroder E, Westphal M, Kunwar S . Poor drug distribution as a possible explanation for the results of the PRECISE trial. J Neurosurg. 2009; 113(2):301-9. DOI: 10.3171/2009.11.JNS091052. View

18.

Gupta S, Thirstrup D, Jarvis T, Schneider D, Wilcox S, Carter J . Rapid histochemistry using slow off-rate modified aptamers with anionic competition. Appl Immunohistochem Mol Morphol. 2011; 19(3):273-8. DOI: 10.1097/PAI.0b013e3182008c29. View

19.

Shao K, Ding W, Wang F, Li H, Ma D, Wang H . Emulsion PCR: a high efficient way of PCR amplification of random DNA libraries in aptamer selection. PLoS One. 2011; 6(9):e24910. PMC: 3174225. DOI: 10.1371/journal.pone.0024910. View

20.

Macdonald J, Denoyer D, Henri J, Jamieson A, Burvenich I, Pouliot N . Bifunctional Aptamer-Doxorubicin Conjugate Crosses the Blood-Brain Barrier and Selectively Delivers Its Payload to EpCAM-Positive Tumor Cells. Nucleic Acid Ther. 2020; 30(2):117-128. PMC: 7133447. DOI: 10.1089/nat.2019.0807. View