Glucose transporter 1-mediated vascular translocation of nanomedicines enhances accumulation and efficacy in solid tumors

Suzuki, Kaoru; Miura, Yutaka; Mochida, Yuki; Miyazaki, Tatsuya; Toh, Kazuko; Anraku, Yasutaka; Melo, Vinicio; Liu, Xueying; Ishii, Takehiko; Nagano, Osamu; Saya, Hideyuki; Cabral, Horacio; Kataoka, Kazunori

doi:10.1016/j.jconrel.2019.02.021

Cited by 68 publications

(56 citation statements)

References 59 publications

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“…As such, we have recently focused our efforts on identifying receptors and transporters expressed on endothelial cells that are associated with metabolic hallmarks of tumors, aiming to design broadly applicable ligand strategies for facilitating extravasation of nanocarriers. To this end, we have developed glucose‐installed polymeric micelles loading cisplatin (Gluc‐CDDP/m) for targeting the glucose transporter 1 (GLUT1), which is overexpressed on tumor vascular endothelial cells, as well as on most cancer cells, due to the glycolytic activity of tumors ( Figure ) . The installation of the glucose moieties promote tumor accumulation through the GLUT1‐glucose mediated vascular translocation.…”

Section: Targeting Strategies With Ligand‐installed Nanocarriersmentioning

confidence: 99%

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Ligand‐Installed Nanocarriers toward Precision Therapy

2019

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Development of drug‐delivery systems that selectively target neoplastic cells has been a major goal of nanomedicine. One major strategy for achieving this milestone is to install ligands on the surface of nanocarriers to enhance delivery to target tissues, as well as to enhance internalization of nanocarriers by target cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding the development of ligand‐installed nanocarriers are introduced and the effect of their design on biological performance is discussed. Besides academic achievements, progress on ligand‐installed nanocarriers in clinical trials is presented, along with the challenges faced by these formulations. Lastly, the future perspectives of ligand‐installed nanocarriers are discussed, with particular emphasis on their potential for emerging precision therapies.

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Section: Targeting Strategies With Ligand‐installed Nanocarriersmentioning

confidence: 99%

Section: Targeting Strategies With Ligand‐installed Nanocarriersmentioning

confidence: 99%

Ligand‐Installed Nanocarriers toward Precision Therapy

2019

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“…For the synthesis of Glu‐PEG‐PLL(MPA/IM), a hetero bifunctional PEG with 1,2:3,5‐di‐ O ‐isopropylidene‐α‐ d ‐glucofuranose at the α‐end, and primary amine at the ω‐end (DIG‐PEG‐NH 2 ), with a molecular weight of the PEG (MW PEG ) of 5300 Da, was synthesized by living anionic polymerization of ethylene oxide initiated with a potassium alkolate of DIG, as previously described (Supporting Information, Figure S1) . The PEG segment was extended from the hydroxyl group at the C6 position of DIG to generate hydroxyl groups at the C1, C3, and C4 positions after deprotection of DIG.…”

Section: Resultsmentioning

confidence: 99%

Systemic Brain Delivery of Antisense Oligonucleotides across the Blood–Brain Barrier with a Glucose‐Coated Polymeric Nanocarrier

et al. 2020

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Current antisense oligonucleotide (ASO) therapies for the treatment of central nervous system (CNS) disorders are performed through invasive administration, thereby placing a major burden on patients. To alleviate this burden, we herein report systemic ASO delivery to the brain by crossing the blood–brain barrier using glycemic control as an external trigger. Glucose‐coated polymeric nanocarriers, which can be bound by glucose transporter‐1 expressed on the brain capillary endothelial cells, are designed for stable encapsulation of ASOs, with a particle size of about 45 nm and an adequate glucose‐ligand density. The optimized nanocarrier efficiently accumulates in the brain tissue 1 h after intravenous administration and exhibits significant knockdown of a target long non‐coding RNA in various brain regions, including the cerebral cortex and hippocampus. These results demonstrate that the glucose‐modified polymeric nanocarriers enable noninvasive ASO administration to the brain for the treatment of CNS disorders.

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“…[ 97 ] In another study, NC‐6004 installed with 25% glucose was fabricated for targeting cancer cells by interacting with the glucose transporter 1 (GLUT1), leading to promoted drug accumulation in tumors and therapeutic efficacy, including both GLUT‐1 high (e.g., OSC‐19) and low tumors (e.g., U87MG). [ 98 ] In addition, NC‐6004 could further be applied for inhibiting metastasis. For instance, it reduced the rate of sentinel lymph node metastasis as tested in an orthotopic tongue cancer model.…”

Section: Self‐assembled Cancer Nanomedicines In Preclinical and Clinimentioning

confidence: 99%

Clinical Translation of Self‐Assembled Cancer Nanomedicines

Miyata

Kataoka

et al. 2020

Advanced Therapeutics

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Nanomedicines are emerging as effective approaches for developing new strategies against cancer. Nanomedicines can be designed for selectively delivering probes and anticancer agents to tumors for achieving improved diagnostic or therapeutic efficacy, while relieving potential side effects. In particular, the number of formulations based on self‐assembled nanostructures under clinical evaluation is increasing due to their unique advantages for elegant and facile preparation, working at the biointerface and spatiotemporally controlling the function of drugs. Here, the current status of clinically used self‐assembled nanomedicines is presented, and recent advances of candidates in clinical trials are reviewed. In addition, the challenges and future prospects of nanomedicines in the clinic are discussed.

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Glucose transporter 1-mediated vascular translocation of nanomedicines enhances accumulation and efficacy in solid tumors

Cited by 68 publications

References 59 publications

Ligand‐Installed Nanocarriers toward Precision Therapy

Ligand‐Installed Nanocarriers toward Precision Therapy

Systemic Brain Delivery of Antisense Oligonucleotides across the Blood–Brain Barrier with a Glucose‐Coated Polymeric Nanocarrier

Clinical Translation of Self‐Assembled Cancer Nanomedicines

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