Fluorescence Correlation Spectroscopy Monitors the Fate of Degradable Nanocarriers in the Blood Stream

Overview

Journal Biomacromolecules

Publisher American Chemical Society

Specialties Biochemistry
Biology
Molecular Biology

Date 2022 Jan 21

PMID 35061359

Authors

Sascha Schmitt

Anne Huppertsberg

Adrian Klefenz

Leonard Kaps

Volker Mailander

Detlef Schuppan

Hans-Jurgen Butt

Lutz Nuhn

Kaloian Koynov

Affiliations

Soon will be listed here.

Abstract

The use of nanoparticles as carriers to deliver pharmacologically active compounds to specific parts of the body via the bloodstream is a promising therapeutic approach for the effective treatment of various diseases. To reach their target sites, nanocarriers (NCs) need to circulate in the bloodstream for prolonged periods without aggregation, degradation, or cargo loss. However, it is very difficult to identify and monitor small-sized NCs and their cargo in the dense and highly complex blood environment. Here, we present a new fluorescence correlation spectroscopy-based method that allows the precise characterization of fluorescently labeled NCs in samples of less than 50 μL of whole blood. The NC size, concentration, and loading efficiency can be measured to evaluate circulation times, stability, or premature drug release. We apply the new method to follow the fate of pH-degradable fluorescent cargo-loaded nanogels in the blood of live mice for periods of up to 72 h.

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References

Martinez-Negro M, Gonzalez-Rubio G, Aicart E, Landfester K, Guerrero-Martinez A, Junquera E . Insights into colloidal nanoparticle-protein corona interactions for nanomedicine applications. Adv Colloid Interface Sci. 2021; 289:102366. DOI: 10.1016/j.cis.2021.102366. View

Klymchenko A, Liu F, Collot M, Anton N . Dye-Loaded Nanoemulsions: Biomimetic Fluorescent Nanocarriers for Bioimaging and Nanomedicine. Adv Healthc Mater. 2020; 10(1):e2001289. DOI: 10.1002/adhm.202001289. View

Kristensen K, Urquhart A, Thormann E, Andresen T . Binding of human serum albumin to PEGylated liposomes: insights into binding numbers and dynamics by fluorescence correlation spectroscopy. Nanoscale. 2016; 8(47):19726-19736. DOI: 10.1039/c6nr05455b. View

Leber N, Kaps L, Aslam M, Schupp J, Brose A, Schaffel D . SiRNA-mediated in vivo gene knockdown by acid-degradable cationic nanohydrogel particles. J Control Release. 2016; 248:10-23. DOI: 10.1016/j.jconrel.2016.12.006. View

Saito E, Kuo R, Kramer K, Gohel N, Giles D, Moore B . Design of biodegradable nanoparticles to modulate phenotypes of antigen-presenting cells for antigen-specific treatment of autoimmune disease. Biomaterials. 2019; 222:119432. PMC: 6830542. DOI: 10.1016/j.biomaterials.2019.119432. View

Kramer S, Svatunek D, Alberg I, Grafen B, Schmitt S, Braun L . HPMA-Based Nanoparticles for Fast, Bioorthogonal iEDDA Ligation. Biomacromolecules. 2019; 20(10):3786-3797. PMC: 6794642. DOI: 10.1021/acs.biomac.9b00868. View

Krieger J, Singh A, Bag N, Garbe C, Saunders T, Langowski J . Imaging fluorescence (cross-) correlation spectroscopy in live cells and organisms. Nat Protoc. 2015; 10(12):1948-74. DOI: 10.1038/nprot.2015.100. View

Wang H, Shang L, Maffre P, Hohmann S, Kirschhofer F, Brenner-Weiss G . The Nature of a Hard Protein Corona Forming on Quantum Dots Exposed to Human Blood Serum. Small. 2016; 12(42):5836-5844. DOI: 10.1002/smll.201602283. View

Sahin U, Oehm P, Derhovanessian E, Jabulowsky R, Vormehr M, Gold M . An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020; 585(7823):107-112. DOI: 10.1038/s41586-020-2537-9. View

10.

Dakwar G, Zagato E, Delanghe J, Hobel S, Aigner A, Denys H . Colloidal stability of nano-sized particles in the peritoneal fluid: towards optimizing drug delivery systems for intraperitoneal therapy. Acta Biomater. 2014; 10(7):2965-75. DOI: 10.1016/j.actbio.2014.03.012. View

11.

Kaps L, Leber N, Klefenz A, Choteschovsky N, Zentel R, Nuhn L . In Vivo siRNA Delivery to Immunosuppressive Liver Macrophages by α-Mannosyl-Functionalized Cationic Nanohydrogel Particles. Cells. 2020; 9(8). PMC: 7465192. DOI: 10.3390/cells9081905. View

12.

Talelli M, Barz M, Rijcken C, Kiessling F, Hennink W, Lammers T . Core-Crosslinked Polymeric Micelles: Principles, Preparation, Biomedical Applications and Clinical Translation. Nano Today. 2015; 10(1):93-117. PMC: 4398985. DOI: 10.1016/j.nantod.2015.01.005. View

13.

Guindani C, Frey M, Simon J, Koynov K, Schultze J, Ferreira S . Covalently Binding of Bovine Serum Albumin to Unsaturated Poly(Globalide-Co-ε-Caprolactone) Nanoparticles by Thiol-Ene Reactions. Macromol Biosci. 2019; 19(10):e1900145. DOI: 10.1002/mabi.201900145. View

14.

Kim S, Schwille P . Intracellular applications of fluorescence correlation spectroscopy: prospects for neuroscience. Curr Opin Neurobiol. 2003; 13(5):583-90. DOI: 10.1016/j.conb.2003.09.002. View

15.

Motealleh A, Dorri P, Kehr N . Self-assembled monolayers of chiral periodic mesoporous organosilica as a stimuli responsive local drug delivery system. J Mater Chem B. 2020; 7(14):2362-2371. DOI: 10.1039/c8tb02507j. View

16.

Bouchaala R, Richert L, Anton N, Vandamme T, Djabi S, Mely Y . Quantifying Release from Lipid Nanocarriers by Fluorescence Correlation Spectroscopy. ACS Omega. 2018; 3(10):14333-14340. PMC: 6210065. DOI: 10.1021/acsomega.8b01488. View

17.

Lippok S, Radtke M, Obser T, Kleemeier L, Schneppenheim R, Budde U . Shear-Induced Unfolding and Enzymatic Cleavage of Full-Length VWF Multimers. Biophys J. 2016; 110(3):545-554. PMC: 4744175. DOI: 10.1016/j.bpj.2015.12.023. View

18.

Kockelmann J, Stickdorn J, Kasmi S, De Vrieze J, Pieszka M, Ng D . Control over Imidazoquinoline Immune Stimulation by pH-Degradable Poly(norbornene) Nanogels. Biomacromolecules. 2020; 21(6):2246-2257. PMC: 7304817. DOI: 10.1021/acs.biomac.0c00205. View

19.

Li H, Van Herck S, Liu Y, Hao Y, Ding X, Nuhn L . Imidazoquinoline-Conjugated Degradable Coacervate Conjugate for Local Cancer Immunotherapy. ACS Biomater Sci Eng. 2021; 6(9):4993-5000. DOI: 10.1021/acsbiomaterials.0c00485. View

20.

Jimenez Calvente C, Sehgal A, Popov Y, Kim Y, Zevallos V, Sahin U . Specific hepatic delivery of procollagen α1(I) small interfering RNA in lipid-like nanoparticles resolves liver fibrosis. Hepatology. 2015; 62(4):1285-97. PMC: 4589454. DOI: 10.1002/hep.27936. View