Cell-specific drug targeting in the lung

Abed, Soumeya; Turner, Rebecca A.; Serniuck, Nickolas; Tat, Victor; Naiel, Safaa; Hayat, Aaron; Mekhael, Olivia; Vierhout, Megan; Ask, Kjetil; Rullo, Anthony

doi:10.1016/j.bcp.2021.114577

Cited by 10 publications

(6 citation statements)

References 140 publications

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“…This study complements different approaches based on other haptens or labelling methods [46] . Compared to other approaches such as ARMs or polymeric systems, [21–26,41–54] this approach presents the flexibility of a two‐step glycoengineering/labelling approach. Furthermore, the general approach described here could be leveraged by selective metabolic glycoengineering strategies targeting specifically cancer cells [34,35,46,47] .…”

Section: Discussionmentioning

confidence: 86%

“…This study complements different approaches based on other haptens or labelling methods. [46] Compared to other approaches such as ARMs or polymeric systems, [21][22][23][24][25][26][41][42][43][44][45][46][47][48][49][50][51][52][53][54] this approach presents the flexibility of a twostep glycoengineering/labelling approach. Furthermore, the…”

Section: Discussionmentioning

confidence: 99%

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Antibody Recognition of Cancer Cells via Glycan Surface Engineering

Szponarski

Gademann

2022

ChemBioChem

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Stimulation of the body's immune system toward tumor cells is now well recognized as a promising strategy in cancer therapy. Just behind cell therapy and monoclonal antibodies, small molecule-based strategies are receiving growing attention as alternatives to direct immune response against tumor cells. However, the development of small-molecule approaches to modulate the balance between stimulatory immune factors and suppressive factors in a targeted way remains a challenge. Here, we report the cell surface functionalization of LS174T cancer cells with an abiotic hapten to recruit antibodies to the cell surface. Metabolic glycoengineering followed by covalent reaction with the hapten results in antibody recognition of the target cells. Microscopy and flow cytometry studies provide compelling evidence that metabolic glycoengineering and small molecule stimulators can be combined to direct antibody recognition.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Antibody Recognition of Cancer Cells via Glycan Surface Engineering

Szponarski

Gademann

2022

ChemBioChem

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“…Similarly, the pulmonary route of administration through inhalation could be an interesting alternative because of the thin epithelial barrier and large surface area of the lungs [ 519 ], and lower expression of metabolic enzymes compared to the liver [ 519 , 520 ]. While drug transporters are expressed in mammalian airway epithelia, their exploitation through rational design to enhance delivery has remained scarce [ 521 , 522 , 523 ].…”

Section: Discussionmentioning

confidence: 99%

Transporter-Mediated Drug Delivery

Gyimesi

Hediger

2023

Molecules

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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 was recognized early on 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 compositions has recently been used as a means to enhance their targeting and 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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“…In recent years, a considerable amount of research on the resistance and sensitization of tumor RT, chemotherapy, immunotherapy, and targeted therapy has emerged, especially in the field of nanomaterials and small biological molecules (23)(24)(25)(26). In our team's previous work, we successfully constructed the recombinant protein iRGD- antiCD3 and demonstrated its antitumor efficacy by promoting T cell activation and infiltration.…”

Section: Discussionmentioning

confidence: 99%

Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma

Zhou¹,

Liu²,

Meng³

et al. 2022

J Gastrointest Oncol

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Background: Radiation resistance remains the leading cause of radiotherapy (RT) failure. The development of tumor-specific targeted sensitizers is key to overcoming radiation resistance. Our early data showed that cancer cell penetration was simulated by internalizing arginine-glycine-aspartic acid (iRGD), and the irradiation efficacy was improved. The present study aims to design and fabricate iRGD-modified red blood cell (RBCs) for tumor targeting and RT enhancement, and to evaluate its safety and efficacy in vivo.Methods: 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-poly ethylene glycol-iRGD (DSPE-PEG-iRGD) was used to modify RBCs by a lipid-insertion method without direct chemical bioconjugation.Fluorescent dyes were used to trace the functional RBCs through confocal microscopy examination. In vitro stability evaluation was performed using cell culture medium incubation for 48 h followed by fluorescence decay assay. Furthermore, a subcutaneous cancer cell mouse model was constructed with MKN-45 cells for target efficacy and RT enhancement evaluation with DSPE-PEG-iRGD-modified RBCs (RBC-iRGD).Results: Successful construction of RBC-iRGD was verified by the presence of the yellow fluorescence, and an approximately 10 8 iRGD molecules were labeled on a single RBC. The final RBC-iRGD showed good stability without any hemolytic effects in the cell culture medium. Moreover, higher fluorescence intensity and decreased liver and spleen accumulation could be observed in RBC-iRGD compared to RBC + iRGD in vivo. The RBC-iRGD exerted enhanced radiosensitivity in subcutaneous gastric tumor mice. Conclusions:The RBC-iRGD exerted good tumor-targeting efficacy and favorable effects for RT enhancement in vivo.

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Cell-specific drug targeting in the lung

Cited by 10 publications

References 140 publications

Antibody Recognition of Cancer Cells via Glycan Surface Engineering

Antibody Recognition of Cancer Cells via Glycan Surface Engineering

Transporter-Mediated Drug Delivery

Modification of erythrocytes by internalizing Arg-Gly-Asp (iRGD) in boosting the curative effect of radiotherapy for gastric carcinoma

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