Biotin conjugates in targeted drug delivery: is it mediated by a biotin transporter, a yet to be identified receptor, or (an)other unknown mechanism(s)?

Biotin Homeostasis and Human Disorders: Recent Findings and Perspectives

“…The MCT family of proteins belongs to the proton-dependent transport protein family (SLC16A), with 14 members based on sequence homology. These transporters have been reported to mediate the uptake of short-chain monocarboxylates such as lactate, α-hydroxybutyrate, pyruvate, and biotin in mammalian cells [ 21 , 27 ].…”

“…In another recent study, a novel near-infrared tracer conjugated to coenzyme-R (i.e., vitamin B7/biotin) was preclinically evaluated for the detection of metabolically active cancerous cells; as revealed, the so-called (CR)-S0456 novel tracer specifically labels highly proliferative tumors through SMVT transport channels and might be further evaluated in human clinical trials for intraoperative molecular imaging-guided resections [ 169 ]. It should be mentioned here that in a recently published article [ 27 ], the authors interestingly drew attention to the previous finding that the free carboxyl group of biotin plays a crucial role in the SMVT-mediated uptake of the molecule, while chemical modification, e.g., to an amide or ester group (as it occurs in most of the biotin conjugates targeting SMVT), has been reported to prevent uptake. This apparent controversy indicates, according to the authors, that further studies are necessary to elucidate the exact cellular uptake mechanisms of biotin conjugates [ 27 ].…”

“…It should be mentioned here that in a recently published article [ 27 ], the authors interestingly drew attention to the previous finding that the free carboxyl group of biotin plays a crucial role in the SMVT-mediated uptake of the molecule, while chemical modification, e.g., to an amide or ester group (as it occurs in most of the biotin conjugates targeting SMVT), has been reported to prevent uptake. This apparent controversy indicates, according to the authors, that further studies are necessary to elucidate the exact cellular uptake mechanisms of biotin conjugates [ 27 ].…”

“…Functionally, SMVT transports dissolved biomolecules such as biotin across the cell membrane against an electrochemical gradient of Na + . As reported, one biotin molecule is co-transported with two sodium ions in a single transport cycle [24][25][26][27].…”

“…have been reported to mediate the uptake of short-chain monocarboxylates such as lactate, α-hydroxybutyrate, pyruvate, and biotin in mammalian cells [21,27].…”