Emerging transporter-targeted nanoparticulate drug delivery systems

Abstract

Transporter-targeted nanoparticulate drug delivery systems (nano-DDS) have emerged as promising nanoplatforms for efficient drug delivery. Recently, great progress in transporter-targeted strategies has been made, especially with the rapid developments in nanotherapeutics. In this review, we outline the recent advances in transporter-targeted nano-DDS. First, the emerging transporter-targeted nano-DDS developed to facilitate oral drug delivery are reviewed. These include improvements in the oral absorption of protein and peptide drugs, facilitating the intravenous-to-oral switch in cancer chemotherapy. Secondly, the recent advances in transporter-assisted brain-targeting nano-DDS are discussed, focusing on the specific transporter-based targeting strategies. Recent developments in transporter-mediated tumor-targeting drug delivery are also discussed. Finally, the possible transport mechanisms involved in transporter-mediated endocytosis are highlighted, with special attention to the latest findings of the interactions between membrane transporters and nano-DDS.

Keywords: Brain-targeting; Nano-DDS; Oral delivery; Transporter; Tumor-targeting.

Graphical abstract

Figure 1

Emerging trends in the fields of transporter-targeted nano-DDS.

Figure 2

Schematic illustration of transepithelial transport of insulin from DNPs to overcome multiple barriers of the intestinal epithelium by exploiting the bile acid pathway. Reprinted with the permission from Ref. . Copyright © 2017 Elsevier Ltd. DNPs, deoxycholic acid-modified nanoparticles; ASBT, apical sodium-dependent bile acid transporter.

Figure 3

Graphic illustration of the composition of l-carnitine-conjugated nanoparticles with varied lengths of PEG spacers, and OCTN2-mediated BBB transcytosis and glioma targeting. Reprinted with the permission from Ref. 68. Copyright © 2017 Taylor & Francis Group.

Figure 4

Illustration of stepwise synthesis, GLUT1-mediated endocytosis and GSH-triggered 3 intracellular drug release of DPL(s-s)P/DOX micelles. Reprinted with the permission from Ref. . Copyright © 2015 American Chemical Society.

Figure 5

(A) Competitive study in hPepT1-Hela cells in the presence of typical substrate GlySar (GS); (B) Influence of proton in the culture medium on the cellular uptake of dipeptide modified NPs in hPepT1-Hela cells; The variation of relative PepT1 mRNA expression versus β-actin (C) and the variations of membrane and cytosol PepT1 protein expression (D,E) after treatments with NSPV1000 NPs for different time over 24 h. Data are shown as mean±SD. ^*P<0.05,^**P<0.01 vs. C6/DTX solution group or control group, ^#P<0.05, ^##P<0.01, n=3; (F) The schematic illustration of hypothesized mechanism of PepT1-mediated endocytosis. Reprinted with the permission from Ref. . Copyright © 2018 Taylor & Francis Group.