Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy

Li, Lin; Di, Xingsheng; Wu, Mingrui; Sun, Zhisu; Liu, Zhong; Wang, Yongjun; Fu, Qiang; Kan, Qiming; Sun, Jin; Zhang, He

doi:10.1016/j.nano.2016.11.012

Cited by 66 publications

(52 citation statements)

References 29 publications

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“…We manipulated the length of PEG for conjugation of L -carnitine to investigate the role of PEG linker in the interaction of the conjugated substrate with OCTN2; the uptake of L -carnitine-conjugated nanoparticles increased with the length of PEG to a certain degree, but then decreased with further increase in the length ( Kou et al, 2017a ). A similar phenomenon was also observed by other investigators ( Xie et al, 2012 ; Li et al, 2017 ).…”

Section: Effects Of Physicochemical Properties Of Nanoparticles On Thsupporting

confidence: 91%

“…These data suggested that glutamate conjugation to nanodevices via its side chain preserves the interaction of the modified amino acid with LAT1. We evaluated the use of such liposomes for tumor-targeted drug delivery ( Li et al, 2017 ). Glutamate-conjugation significantly increased the cellular uptake and cytotoxicity of nanoparticles in HeLa (a human cervical cancer cell line) and MCF7 (a human estrogen receptor-positive breast cancer cell line) cells, both of which show robust expression of LAT1.…”

Section: Transporter-assisted Nano-drug Delivery Systemsmentioning

confidence: 99%

“…As for nanoparticles or macromolecular conjugates, the transporter-assisted transfer process works differently; the mechanism is more like receptor-mediated transport. We have elucidated the probable mechanism of transporter-assisted uptake of nanoparticles ( Luo et al, 2016 ; Kou et al, 2017c ; Li et al, 2017 ). Substrate-conjugated nanoparticles bind to the targeted transporters on the outside along with co-transported ions if involved, but the macromolecular nature of the nanoparticles prevents the four-step transfer mechanism described above for small molecule substrates.…”

Section: Cellular Trafficking Of Transporter-targeted Nanoparticlesmentioning

confidence: 99%

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Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

et al. 2018

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Targeted nano-drug delivery systems conjugated with specific ligands to target selective cell-surface receptors or transporters could enhance the efficacy of drug delivery and therapy. Transporters are expressed differentially on the cell-surface of different cell types, and also specific transporters are expressed at higher than normal levels in selective cell types under pathological conditions. They also play a key role in intestinal absorption, delivery via non-oral routes (e.g., pulmonary route and nasal route), and transfer across biological barriers (e.g., blood–brain barrier and blood–retinal barrier. As such, the cell-surface transporters represent ideal targets for nano-drug delivery systems to facilitate drug delivery to selective cell types under normal or pathological conditions and also to avoid off-target adverse side effects of the drugs. There is increasing evidence in recent years supporting the utility of cell-surface transporters in the field of nano-drug delivery to increase oral bioavailability, to improve transfer across the blood–brain barrier, and to enhance delivery of therapeutics in a cell-type selective manner in disease states. Here we provide a comprehensive review of recent advancements in this interesting and important area. We also highlight certain key aspects that need to be taken into account for optimal development of transporter-assisted nano-drug delivery systems.

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Section: Effects Of Physicochemical Properties Of Nanoparticles On Thsupporting

confidence: 91%

Section: Transporter-assisted Nano-drug Delivery Systemsmentioning

confidence: 99%

Section: Cellular Trafficking Of Transporter-targeted Nanoparticlesmentioning

confidence: 99%

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Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

et al. 2018

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“…The past thirty years have seen progressively rapid developments in the field of targeted anticancer drugs. The baseline of this field depends mainly on two major methods, passive and active process [2,[7][8][9][10][11]. The former relates directly to the nature of tumor capillary vessels, and the later depends on the interaction mechanism with cancer cells.…”

Section: Role Of Targeting Systemmentioning

confidence: 99%

The Impact of New Targeting Methods in the Cancer Therapy

2019

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Rapid development has achieved in treating tumor to stop malignant cell growth and metastasis in the past decade. Numerous researches have emerged to increase potency and efficacy with novel methods for drug delivery. The main objective of this literature review was to illustrate the impact of current new targeting methods to other previous delivering systems to select the most appropriate method in cancer therapy. This review first gave a brief summary of cancer structure and highlighted the main roles of targeting systems. Different types of delivering systems have been addressed in this literature review with focusing on the latest carrier derived from malarial protein. The remarkable advantages and main limitations of the later have been also discussed. PubMed and Science Direct were the main search engines that have been used as information sources to prepare this review. Articles related to cancer targeting system, active and passive processes, current nanoparticles, antibody carriers, and current novel cancer carriers were used as sources in this review. Important points from many references published in the last decade (2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018) were selected and included. Several targeting methods were introduced to enhance the efficacy and tolerability of the toxic drug by active and passive processes, but there is still no conclusive carrier without certain drawbacks. A combination of targeting methods probably shows the most appropriate choice for increasing selectivity and safety of anticancer drugs via reducing the concentration of carriers used. I In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f A Ap pp pl li ie ed d P Ph ha ar rm ma ac ce eu ut ti ic cs s

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“…Research work has indicated that NPs modified with endogenous substrates targeted to the transporters on the surface of certain tumour cells are proposed to facilitate the cellular uptake and targeting efficiency. This strategy involves facilitative glucose transporter 1 (GLUT1and SLC2A1), Na þ /Cl À -coupled amino acid transporter (ATB 0,þ and SLC6A14), facilitative amino acid exchanger large neutral amino acid transporter (LAT1 and SLC7A5) and so on [14][15][16][17][18][19]. What's more, in the latest progress of our research, we found that L-carnitine-conjugated nanoparticles (LC-PLGA NPs) selectively targeted to organic cation transporter 2 (OCTN2 and SLC22A5) on the enterocytes for enhancing oral delivery of drugs [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Ascorbate-conjugated nanoparticles for promoted oral delivery of therapeutic drugs via sodium-dependent vitamin C transporter 1 (SVCT1)

Luo

Jiang

Kou

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Oral administration is the most convenient route for most patients. However, many therapeutics in clinical applications are limited due to the poor solubility and permeability as well as low stability in the intestinal tract. It still remains a significant challenge of how to improve the oral drug bioavailability. In this study, we have designed functional ascorbate-conjugated NPs (As-PLGA NPs) to offer the interaction with sodium-dependent vitamin C transporter 1 (SVCT1) on the epithelial cells. Cellular uptake study indicated that conjugation of 20% ascorbate to the surface of PLGA NPs might achieve a maximum efficacy in Caco-2 cells. Besides, the majority of As-PLGA NPs were predominantly internalized into cells via caveolae-mediated pathway and thereby circumnavigated the lysosomal compartment. Furthermore, the competitive inhibition test and Na þ-dependent study provide strong evidence that SVCT1 was involved in the internalization of As-PLGA NPs. Finally, the biodistribution and perfusion study demonstrated that As-PLGA NPs accumulated in the villi and penetrated to the basolateral side, thus significantly enhanced the intestinal absorption. In summary, it showed that SVCT1 expressed in the apical side of epithelial cells might be conceivably exploited as a potential target for oral delivery of therapeutic drug-loaded pharmaceutical nanocarriers. By means of the interaction of SVCT1 and ascorbate on the surface of PLGA NPs, the nanoparticles and transporters accumulated in coated pits, internalizing as ligand-transporter complexes and switched the subcellular sorting of NPs.

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Targeting tumor highly-expressed LAT1 transporter with amino acid-modified nanoparticles: Toward a novel active targeting strategy in breast cancer therapy

Cited by 66 publications

References 29 publications

Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

Transporter-Guided Delivery of Nanoparticles to Improve Drug Permeation across Cellular Barriers and Drug Exposure to Selective Cell Types

The Impact of New Targeting Methods in the Cancer Therapy

Ascorbate-conjugated nanoparticles for promoted oral delivery of therapeutic drugs via sodium-dependent vitamin C transporter 1 (SVCT1)

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