Tyrosine modified irinotecan-loaded liposomes capable of simultaneously targeting LAT1 and ATB0,+ for efficient tumor therapy

Wang, Zhenjie; Chi, Dongxu; Wu, Xingchen; Wang, Yingli; Lin, Xinxin; Xu, Zhaochu; Liu, Hongzhuo; Sun, Jin; Zhang, He; Wang, Yongjun

doi:10.1016/j.jconrel.2019.10.037

Cited by 33 publications

(18 citation statements)

References 25 publications

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“…The tumor inhibition rate of the tyrosine-functionalized liposomes was also higher than that of unfunctionalized liposome formulations. The mechanism of uptake was confirmed as LAT1-and SLC6A14-mediated endocytosis [125].…”

Section: Amino Acid Transportersmentioning

confidence: 85%

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Transporter-Mediated Drug Delivery

Gyimesi¹,

Hediger²

2022

Preprint

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Transmembrane transport of small organic and inorganic molecules is one of the cornerstones of cellular metabolism. Among transmembrane transporters, solute carrier (SLC) proteins form the largest, albeit very diverse, superfamily with over 400 members. It has been early on recognized that xenobiotics can directly interact with SLCs and that this interaction can fundamentally determine their efficacy, including bioavailability and intertissue distribution. Apart from the well-established prodrug strategy, the chemical ligation of transporter substrates to nanoparticles of various chemical composition has recently been used as a means to enhance their targeting or absorption. In this review, we summarize efforts in drug design exploiting interactions with specific SLC transporters to optimize their therapeutic effects. Furthermore, we describe current and future challenges as well as new directions for the advanced development of therapeutics that target SLC transporters.

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Section: Amino Acid Transportersmentioning

confidence: 85%

“…Attempts were also made to target both LAT1 and SLC6A14 with a single nanoparticle [125]. Liposomes loaded with irinotecan were functionalized with polyethylene glycol monostearate conjugated with different amino acids.…”

Section: Amino Acid Transportersmentioning

confidence: 99%

Transporter-Mediated Drug Delivery

Gyimesi¹,

Hediger²

2022

Preprint

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“…However, the prepared liposomes should have a controlled size and surface decorated with target-specific antibodies [ 27 ]. For example, the tyrosine-modified irinotecan-loaded liposomes targeting LAT1 and ATB 0,+ showed good prospects for tumor therapy and industrial production [ 28 ]. Liposomes have been widely described as efficient drug delivery systems in many studies.…”

Section: Discussionmentioning

confidence: 99%

Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes

Liu¹,

Li²,

Pen³

et al. 2022

BioMed Eng OnLine

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Background CPT-11 (irinotecan) is one of the most efficient agents used for colorectal cancer chemotherapy. However, as for many other chemotherapeutic drugs, how to minimize the side effects of CPT-11 still needs to be thoroughly described. Objectives This study aimed to develop the CPT-11-loaded DSPE-PEG 2000 targeting EGFR liposomal delivery system and characterize its targeting specificity and therapeutic effect on colorectal cancer (CRC) cells in vitro and in vivo. Results The synthesized liposome exhibited spherical shapes (84.6 ± 1.2 nm to 150.4 nm ± 0.8 nm of estimated average sizes), good stability, sustained release, and enough drug loading (55.19%). For in vitro experiments, SW620 cells treated with CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome showed lower survival extended level of intracellular ROS production. In addition, it generated an enhanced apoptotic cell rate by upregulating the protein expression of both cleaved-caspase-3 and cleaved-caspase-9 compared with those of SW620 cells treated with free CPT-11. Importantly, the xenograft model showed that both the non-target and EGFR-targeted liposomes significantly inhibited tumor growth compared to free CPT-11. Conclusions Compared with the non-target CPT-11-loaded DSPE-PEG2000 liposome, CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome treatment showed much better antitumor activity in vitro in vivo. Thus, our findings provide new assets and expectations for CRC targeting therapy.

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“…To investigate the interaction of nanoparticles with specific target, the colocalization assay was performed as previously reported [ 27 ]. Briefly, MCF7 cells were cultured on 12-mm cover glasses in 12-well plate with a density of 3 × 10 5 cells/well for 24 h. Subsequently, the medium was removed, and the cells were replenished with fresh DMEM containing C6@NPs, C6@Trp-NPs, C6@Gln-NPs or C6@Lys-NPs, respectively, at the same C6 concentration (4 μg/mL).…”

Section: Methodsmentioning

confidence: 99%

Resetting amino acid metabolism of cancer cells by ATB0,+-targeted nanoparticles for enhanced anticancer therapy

Kou

Jiang

Tang

et al. 2022

Bioactive Materials

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Reprogramed cellular metabolism is one of the most significant hallmarks of cancer. All cancer cells exhibit increased demand for specific amino acids, and become dependent on either an exogenous supply or upregulated de novo synthesis. The resultant enhanced availability of amino acids supports the reprogramed metabolic pathways and fuels the malignant growth and metastasis of cancers by providing energy and critical metabolic intermediates, facilitating anabolism, and activating signaling networks related to cell proliferation and growth. Therefore, pharmacologic blockade of amino acid entry into cancer cells is likely to have a detrimental effect on cancer cell growth. Here we developed a nanoplatform (LJ@Trp-NPs) to therapeutically target two transporters, SLC6A14 (ATB 0,+ ) and SLC7A5 (LAT1), that are known to be essential for the sustenance of amino acid metabolism in most cancers. The LJ@Trp-NPs uses tryptophan to guide SLC6A14-targeted delivery of JPH203, a high-affinity inhibitor of SLC7A5. In the process, SLC6A14 is also down-regulated. We tested the ability of this strategy to synergize with the anticancer efficacy of lapatinib, an inhibitor of EGFR/HER1/HER2-assocated kinase. These studies show that blockade of amino acid entry amplifies the anticancer effect of lapatinib via interference with mTOR signaling, promotion of apoptosis, and suppression of cell proliferation and metastasis. This represents the first study to evaluate the impact of amino acid starvation on the anticancer efficacy of widely used kinase inhibitor.

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Tyrosine modified irinotecan-loaded liposomes capable of simultaneously targeting LAT1 and ATB0,+ for efficient tumor therapy

Cited by 33 publications

References 25 publications

Transporter-Mediated Drug Delivery

Transporter-Mediated Drug Delivery

Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes

Resetting amino acid metabolism of cancer cells by ATB0,+-targeted nanoparticles for enhanced anticancer therapy

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