Disabling partners in crime: Gold nanoparticles disrupt multicellular communications within the tumor microenvironment to inhibit ovarian tumor aggressiveness

Zhang, Yushan; Elechalawar, Chandra Kumar; Yang, Wen; Frickenstein, Alex N.; Asfa, Sima; Fung, Kar‐Ming; Murphy, Brennah; Dwivedi, Shailendra Kumar Dhar; Rao, Geeta; Dey, Anindya; Wilhelm, Stefan; Bhattacharya, Resham; Mukherjee, Priyabrata

doi:10.1016/j.mattod.2022.01.025

Cited by 7 publications

(4 citation statements)

References 60 publications

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“…The ovarian cancer cell line, OV90, induced about 7 microvessels per image field at 200x magnification in nude mice. [ 46 ] When seeded in the ultra‐low attachment (ULA) plate, OV90 was able to form tumor spheroids alone (Figure S4a, Supporting Information). In the co‐mixed tumor spheroid, the majority of FBs gathered in the center of the tumor spheroid, with few FBs located at the periphery (Figure S4a, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay

Wan

Floryan

Coughlin

et al. 2022

Adv Healthcare Materials

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Previous studies have developed vascularized tumor spheroid models to demonstrate the impact of intravascular flow on tumor progression and treatment. However, these models have not been widely adopted so the vascularization of tumor spheroids in vitro is generally lower than vascularized tumor tissues in vivo. To improve the tumor vascularization level, a new strategy is introduced to form tumor spheroids by adding fibroblasts (FBs) sequentially to a pre-formed tumor spheroid and demonstrate this method with tumor cell lines from kidney, lung, and ovary cancer. Tumor spheroids made with the new strategy have higher FB densities on the periphery of the tumor spheroid, which tend to enhance vascularization. The vessels close to the tumor spheroid made with this new strategy are more perfusable than the ones made with other methods. Finally, chimeric antigen receptor (CAR) T cells are perfused under continuous flow into vascularized tumor spheroids to demonstrate immunotherapy evaluation using vascularized tumor-on-a-chip model. This new strategy for establishing tumor spheroids leads to increased vascularization in vitro, allowing for the examination of immune, endothelial, stromal, and tumor cell responses under static or flow conditions.

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Section: Resultsmentioning

confidence: 99%

New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay

Wan

Floryan

Coughlin

et al. 2022

Adv Healthcare Materials

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“…The ability of GNP to inhibit HB-GFs has shown promise to inhibit tumor growth, metastasis, and therapy resistance in a number of cancers. ,, GNP have also been used as a therapeutic molecule in a number of noncancerous diseases including rheumatoid arthritis, diseases of the eye, and neurodegenerative diseases such as Alzheimer’s disease. − However, the ability of GNP to modulate KRAS activation and macropinocytosis has not yet been tested. Our finding of GNP-mediated inhibition of macropinocytosis and tumor growth in two independent preclinical models of PDAC demonstrates its potential utility to inhibit tumor growth in other malignancies harboring RAS mutations.…”

Section: Discussionmentioning

confidence: 99%

“…The ability of GNP to inhibit HB-GFs has shown promise to inhibit tumor growth, metastasis, and therapy resistance in a number of cancers. 14,23,30 GNP have also been used as a therapeutic molecule in a number of noncancerous diseases including rheumatoid arthritis, diseases of the eye, and neurodegenerative diseases such as Alzheimer's disease. 31−34 However, the ability of GNP to modulate KRAS activation and macropinocytosis has not yet been tested.…”

Section: Discussionmentioning

confidence: 99%

Gold Nanoparticles Inhibit Macropinocytosis by Decreasing KRAS Activation

et al. 2023

Self Cite

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The RAS-transformed cells utilize macropinocytosis to acquire amino acids to support their uncontrolled growth. However, targeting RAS to inhibit macropinocytosis remains a challenge. Here, we report that gold nanoparticles (GNP) inhibit macropinocytosis by decreasing KRAS activation. Using surface-modified and unmodified GNP, we showed that unmodified GNP specifically sequestered both wild-type and mutant KRAS and inhibited its activation, irrespective of growth factor stimulation, while surface-passivated GNP had no effect. Alteration of KRAS activation is reflected on downstream signaling cascades, macropinocytosis and tumor cell growth in vitro, and two independent preclinical human xenograft models of pancreatic cancer in vivo. The current study demonstrates NP-mediated inhibition of macropinocytosis and KRAS activation and provides translational opportunities to inhibit tumor growth in a number of cancers where activation of KRAS plays a major role.

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“…Skóra et al confirmed the possibility of selectively delivering silver NPs to cancer cells by loading them into EGF-decorated liposomes that were able to induce toxicity in cancer cells in vitro [57]. Growth factors and cytokines are also the target of the research published by Zhang et al in June 2022; here, the authors validated the use of gold NPs to inhibit the tumorigenic phenotype and tumor growth both in vitro and in vivo, highlighting the crucial role of soluble hormones in the TME in tumor progression [78]. Another hormone that has been used to target cancer cells is the vascular endothelial growth factor (VEGF).…”

Section: Targeting the Tumor Microenvironment (Tme)mentioning

confidence: 93%

Recent Advances on Surface-Modified GBM Targeted Nanoparticles: Targeting Strategies and Surface Characterization

Rodà

Caraffi

Picciolini

et al. 2023

IJMS

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Glioblastoma multiforme (GBM) is the most common malignant brain tumor, associated with low long-term survival. Nanoparticles (NPs) developed against GBM are a promising strategy to improve current therapies, by enhancing the brain delivery of active molecules and reducing off-target effects. In particular, NPs hold high potential for the targeted delivery of chemotherapeutics both across the blood–brain barrier (BBB) and specifically to GBM cell receptors, pathways, or the tumor microenvironment (TME). In this review, the most recent strategies to deliver drugs to GBM are explored. The main focus is on how surface functionalizations are essential for BBB crossing and for tumor specific targeting. We give a critical analysis of the various ligand-based approaches that have been used to target specific cancer cell receptors and the TME, or to interfere with the signaling pathways of GBM. Despite the increasing application of NPs in the clinical setting, new methods for ligand and surface characterization are needed to optimize the synthesis, as well as to predict their in vivo behavior. An expert opinion is given on the future of this research and what is still missing to create and characterize a functional NP system for improved GBM targeting.

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Disabling partners in crime: Gold nanoparticles disrupt multicellular communications within the tumor microenvironment to inhibit ovarian tumor aggressiveness

Cited by 7 publications

References 60 publications

New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay

New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay

Gold Nanoparticles Inhibit Macropinocytosis by Decreasing KRAS Activation

Recent Advances on Surface-Modified GBM Targeted Nanoparticles: Targeting Strategies and Surface Characterization

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