Abstract
Simple SummaryNano-drug delivery systems serve as Trojan horses to carry therapeutic drugs as cargos and deliver them to target cells. The specificity of these delivery vehicles to a particular cell type can be improved if the surface of the vehicles is chemically modified in such a manner that they are recognized and attracted to the target cell. This can be accomplished if the target cell selectively expresses a receptor or transporter and the surface of the drug-delivery vehicles is conjugated with the receptor agonist or the transporter substrate. In this review, we detail published literature on the successful exploitation of plasma membrane transporters for this purpose. In particular, this review emphasizes the delivery of chemotherapeutic drugs to cancer cells by targeting the nano-delivery systems specifically to certain transporters that are selectively upregulated in cancer cells.Nano-devices are recognized as increasingly attractive to deliver therapeutics to target cells. The specificity of this approach can be improved by modifying the surface of the delivery vehicles such that they are recognized by the target cells. In the past, cell-surface receptors were exploited for this purpose, but plasma membrane transporters also hold similar potential. Selective transporters are often highly expressed in biological barriers (e.g., intestinal barrier, blood–brain barrier, and blood–retinal barrier) in a site-specific manner, and play a key role in the vectorial transfer of nutrients. Similarly, selective transporters are also overexpressed in the plasma membrane of specific cell types under pathological states to meet the biological needs demanded by such conditions. Nano-drug delivery systems could be strategically modified to make them recognizable by these transporters to enhance the transfer of drugs across the biological barriers or to selectively expose specific cell types to therapeutic drugs. Here, we provide a comprehensive review and detailed evaluation of the recent advances in the field of transporter-targeted nano-drug delivery systems. We specifically focus on areas related to intestinal absorption, transfer across blood–brain barrier, tumor-cell selective targeting, ocular drug delivery, identification of the transporters appropriate for this purpose, and details of the rationale for the approach.
Highlights
Nano-drug delivery systems (NDDS) have attracted a lot of attention in recent years due to their unique characteristics, including increased drug solubility and stability, sustained drug release, prolonged life in circulation, reduced toxicity, and enhanced therapeutic efficacy [1,2,3]
Compared to non-modified NPs, DGlu-NPs significantly increased the uptake of the NPs in blood–brain barrier (BBB) endothelial cells; this uptake of functionalized NPs was inhibited by free glucose, providing evidence for the involvement of GLUT1 in the uptake process of DGlu-NPs
A follow-up study showed that the mRNA expression of GLUT1 was significantly upregulated after the first 24 h of treatment of glucose-conjugated nanoparticles, but decreased to 45% of control after 72 h, which coincided with the cell death
Summary
Nano-drug delivery systems (NDDS) have attracted a lot of attention in recent years due to their unique characteristics, including increased drug solubility and stability, sustained drug release, prolonged life in circulation, reduced toxicity, and enhanced therapeutic efficacy [1,2,3]. As most often it is the structural similarity to the natural substrate that determines the interaction of a drug with any given transporter, chemically modifying the drugs could facilitate such interaction, thereby increasing the absorption and distribution of the drugs to maximize their therapeutic efficacy This is the basis of the prodrug approach. The parent drugs, Cancers 2020, 12, x structural similarity to the natural substrate that determines the interaction of a drug with any given transporter, chemically modifying the drugs could facilitate such interaction, thereby increasing the absorption and distribution of the drugs to maximize their therapeutic efficacy. Perspectives and comments for the future direction of transporter-targeted NDDS
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