Riboflavin-Targeted Drug Delivery

Abstract

Active targeting can improve the retention of drugs and drug delivery systems in tumors, thereby enhancing their therapeutic efficacy. In this context, vitamin receptors that are overexpressed in many cancers are promising targets. In the last decade, attention and research were mainly centered on vitamin B9 (folate) targeting; however, the focus is slowly shifting towards vitamin B2 (riboflavin). Interestingly, while the riboflavin carrier protein was discovered in the 1960s, the three riboflavin transporters (RFVT 1-3) were only identified recently. It has been shown that riboflavin transporters and the riboflavin carrier protein are overexpressed in many tumor types, tumor stem cells, and the tumor neovasculature. Furthermore, a clinical study has demonstrated that tumor cells exhibit increased riboflavin metabolism as compared to normal cells. Moreover, riboflavin and its derivatives have been conjugated to ultrasmall iron oxide nanoparticles, polyethylene glycol polymers, dendrimers, and liposomes. These conjugates have shown a high affinity towards tumors in preclinical studies. This review article summarizes knowledge on RFVT expression in healthy and pathological tissues, discusses riboflavin internalization pathways, and provides an overview of RF-targeted diagnostics and therapeutics.

Molecular Delivery of Cytotoxic Agents via Integrin Activation

“…Among targets, folate receptors were the most commonly selected cancer targets, particularly for ovarian cancers [ 10 , 11 ]; the riboflavin receptor, instead, emerged in recent years because carrier protein of vitamin B 2 , and three riboflavin transporters were found overexpressed in several cancers and could be chosen for tumor targeted drug delivery systems [ 12 ]. CD44, a cell surface adhesion receptor for hyaluronic acid (HA), is highly expressed in many cancers and regulates metastasis via recruitment to cell surface; therefore, various HA-based drug delivery systems have been developed for a CD44-mediated tumor targeting [ 13 , 14 ].…”

Toxicological evaluation of highly water dispersible few-layer graphene in vivo

“…[19] Furthermore, tumor cells exhibit increased riboflavin metabolism as compared to normal cells and when riboflavin have been conjugated to ultrasmall iron oxide nanoparticles, polyethylene glycol polymers, dendrimers, and liposomes, they have shown a high affinity towards tumors in preclinical studies. [20] Since graphene related materials are proposed as a prospective platform for therapeutics including cancer therapy, it could be sensible to provide an overview on the toxicological profile of these materials.…”

Molecular engineering of the last-generation CNTs in smart cancer therapy by grafting PEG–PLGA–riboflavin

“…RF deciency due to unbalanced diet may result in oxidative damage, cell cycle arrest, and cell stress response, weakening iron absorption, causing hearing loss, and cranial nerve decits. 11 RF is a micronutrient playing roles in a variety of redox reactions through the cofactors avin mononucleotide (FMN) and avin adenine dinucleotide (FAD), which are essential electron carriers during cellular respiration and energy production. Moreover, the derivatives of RF have been applied as tumor targeting ligands in vitro and in vivo, which has shown the enhanced tumor-specic accumulation of riboavintargeted nanotubes carrying paclitaxel in MCF-7 cells12 as well as riboavin-targeted liposomes in murine A431 and PC3 tumor xenogras.…”