Dendrimers As Antiamyloid Agents

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Apr 23

PMID 35456594

Authors

Svetlana A Sorokina

Zinaida B Shifrina

Affiliations

Soon will be listed here.

Abstract

Dendrimer-protein conjugates have significant prospects for biological applications. The complexation changes the biophysical behavior of both proteins and dendrimers. The dendrimers could influence the secondary structure of proteins, zeta-potential, distribution of charged regions on the surface, the protein-protein interactions, etc. These changes offer significant possibilities for the application of these features in nanotheranostics and biomedicine. Based on the dendrimer-protein interactions, several therapeutic applications of dendrimers have emerged. Thus, the formation of stable complexes retains the disordered proteins on the aggregation, which is especially important in neurodegenerative diseases. To clarify the origin of these properties and assess the efficiency of action, the mechanism of protein-dendrimer interaction and the nature and driving force of binding are considered in this review. The review outlines the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties.

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References

Fischer M, Appelhans D, Schwarz S, Klajnert B, Bryszewska M, Voit B . Influence of surface functionality of poly(propylene imine) dendrimers on protease resistance and propagation of the scrapie prion protein. Biomacromolecules. 2010; 11(5):1314-25. DOI: 10.1021/bm100101s. View

Giehm L, Christensen C, Boas U, Heegaard P, Otzen D . Dendrimers destabilize proteins in a generation-dependent manner involving electrostatic interactions. Biopolymers. 2008; 89(6):522-9. DOI: 10.1002/bip.20921. View

Liu Y, Carver J, Calabrese A, Pukala T . Gallic acid interacts with α-synuclein to prevent the structural collapse necessary for its aggregation. Biochim Biophys Acta. 2014; 1844(9):1481-5. DOI: 10.1016/j.bbapap.2014.04.013. View

Moorthy H, Govindaraju T . Dendrimer Architectonics to Treat Cancer and Neurodegenerative Diseases with Implications in Theranostics and Personalized Medicine. ACS Appl Bio Mater. 2022; 4(2):1115-1139. DOI: 10.1021/acsabm.0c01319. View

Cametti M, Crousse B, Metrangolo P, Milani R, Resnati G . The fluorous effect in biomolecular applications. Chem Soc Rev. 2011; 41(1):31-42. DOI: 10.1039/c1cs15084g. View

Winner B, Jappelli R, Maji S, Desplats P, Boyer L, Aigner S . In vivo demonstration that alpha-synuclein oligomers are toxic. Proc Natl Acad Sci U S A. 2011; 108(10):4194-9. PMC: 3053976. DOI: 10.1073/pnas.1100976108. View

Mroczko B, Groblewska M, Litman-Zawadzka A, Kornhuber J, Lewczuk P . Amyloid β oligomers (AβOs) in Alzheimer's disease. J Neural Transm (Vienna). 2017; 125(2):177-191. DOI: 10.1007/s00702-017-1820-x. View

Yang J, Zhang Q, Chang H, Cheng Y . Surface-engineered dendrimers in gene delivery. Chem Rev. 2015; 115(11):5274-300. DOI: 10.1021/cr500542t. View

Appelhans D, Klajnert-Maculewicz B, Janaszewska A, Lazniewska J, Voit B . Dendritic glycopolymers based on dendritic polyamine scaffolds: view on their synthetic approaches, characteristics and potential for biomedical applications. Chem Soc Rev. 2014; 44(12):3968-96. DOI: 10.1039/c4cs00339j. View

10.

Klajnert B, Cortijo-Arellano M, Cladera J, Bryszewska M . Influence of dendrimer's structure on its activity against amyloid fibril formation. Biochem Biophys Res Commun. 2006; 345(1):21-8. DOI: 10.1016/j.bbrc.2006.04.041. View

11.

Aguzzi A, OConnor T . Protein aggregation diseases: pathogenicity and therapeutic perspectives. Nat Rev Drug Discov. 2010; 9(3):237-48. DOI: 10.1038/nrd3050. View

12.

Citron M . Alzheimer's disease: strategies for disease modification. Nat Rev Drug Discov. 2010; 9(5):387-98. DOI: 10.1038/nrd2896. View

13.

Yellepeddi V, Ghandehari H . Pharmacokinetics of oral therapeutics delivered by dendrimer-based carriers. Expert Opin Drug Deliv. 2019; 16(10):1051-1061. DOI: 10.1080/17425247.2019.1656607. View

14.

Dawson T, Dawson V . Molecular pathways of neurodegeneration in Parkinson's disease. Science. 2003; 302(5646):819-22. DOI: 10.1126/science.1087753. View

15.

Debnath K, Pradhan N, Singh B, Jana N, Jana N . Poly(trehalose) Nanoparticles Prevent Amyloid Aggregation and Suppress Polyglutamine Aggregation in a Huntington's Disease Model Mouse. ACS Appl Mater Interfaces. 2017; 9(28):24126-24139. DOI: 10.1021/acsami.7b06510. View

16.

Sorokina S, Stroylova Y, Shifrina Z, Muronetz V . Disruption of Amyloid Prion Protein Aggregates by Cationic Pyridylphenylene Dendrimers. Macromol Biosci. 2015; 16(2):266-75. DOI: 10.1002/mabi.201500268. View

17.

Caminade A, Turrin C . Dendrimers for drug delivery. J Mater Chem B. 2020; 2(26):4055-4066. DOI: 10.1039/c4tb00171k. View

18.

Inoue M, Ueda M, Higashi T, Anno T, Fujisawa K, Motoyama K . Therapeutic Potential of Polyamidoamine Dendrimer for Amyloidogenic Transthyretin Amyloidosis. ACS Chem Neurosci. 2019; 10(5):2584-2590. DOI: 10.1021/acschemneuro.9b00059. View

19.

Qi R, Gao Y, Tang Y, He R, Liu T, He Y . PEG-conjugated PAMAM dendrimers mediate efficient intramuscular gene expression. AAPS J. 2009; 11(3):395-405. PMC: 2758109. DOI: 10.1208/s12248-009-9116-1. View

20.

Palmerston Mendes L, Pan J, Torchilin V . Dendrimers as Nanocarriers for Nucleic Acid and Drug Delivery in Cancer Therapy. Molecules. 2017; 22(9). PMC: 5600151. DOI: 10.3390/molecules22091401. View