Influence of Riboflavin Targeting on Tumor Accumulation and Internalization of Peptostar Based Drug Delivery Systems

Riboflavin carrier protein (RCP) and riboflavin transporters (RFVTs) have been reported to be highly overexpressed in various cancer cells. Hence, targeting RCP and RFVTs using riboflavin may enhance tumor accumulation and internalization of drug delivery systems. To test this hypothesis, butyl-base...

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Bibliographic Details
Published in:Bioconjugate chemistry 2020-12, Vol.31 (12), p.2691-2696
Main Authors: Darguzyte, Milita, Holm, Regina, Baier, Jasmin, Drude, Natascha, Schultze, Jennifer, Koynov, Kaloian, Schwiertz, David, Dadfar, Seyed Mohammadali, Lammers, Twan, Barz, Matthias, Kiessling, Fabian
Format: Article
Language:English
Subjects:
Accumulation
Biocompatibility
Drug delivery
Drug delivery systems
Fluorescent dyes
Fluorescent indicators
In vivo methods and tests
Internalization
Lysine
Polymers
Protein transport
Riboflavin
Riboflavin carrier protein
Sarcosine
Tumor cells
Tumors
Vitamin B
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Summary:Riboflavin carrier protein (RCP) and riboflavin transporters (RFVTs) have been reported to be highly overexpressed in various cancer cells. Hence, targeting RCP and RFVTs using riboflavin may enhance tumor accumulation and internalization of drug delivery systems. To test this hypothesis, butyl-based 3-arm peptostar polymers were synthesized consisting of a lysine core (10 units per arm) and a sarcosine shell (100 units per arm). The end groups of the arms and the core were successfully modified with riboflavin and the Cy5.5 fluorescent dye, respectively. While in phosphate buffered saline the functionalized peptostars showed a bimodal behavior and formed supramolecular structures over time, they were stable in the serum maintaining their hydrodynamic diameter of 12 nm. Moreover, the polymers were biocompatible and the uptake of riboflavin targeted peptostars in A431 and PC3 cells was higher than in nontargeted controls and could be blocked competitively. In vivo, the polymers showed a moderate passive tumor accumulation, which was not significantly different between targeted and nontargeted peptostars. Nonetheless, at the histological level, internalization into tumor cells was strongly enhanced for the riboflavin-targeted peptostars. Based on these results, we conclude that passive accumulation is dominating the accumulation of peptostars, while tumor cell internalization is strongly promoted by riboflavin targeting.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.0c00593