Gold Nanoparticles Inhibit Macropinocytosis by Decreasing KRAS Activation

Chandra Kumar Elechalawar; Geeta Rao; Suresh Kumar Gulla; Maulin Mukeshchandra Patel; Alex Frickenstein; Nicolas Means; Ram Vinod Roy; Leonidas Tsiokas; Sima Asfa; Prasanta Panja; Chinthalapally Rao; Stefan Wilhelm; Resham Bhattacharya; Priyabrata Mukherjee

doi:10.1021/acsnano.3c00920

journal article·2023-05-23Open access

Gold Nanoparticles Inhibit Macropinocytosis by Decreasing KRAS Activation

Chandra Kumar Elechalawar, Geeta Rao, Suresh Kumar Gulla, Maulin Mukeshchandra Patel, Alex Frickenstein, Nicolas Means, Ram Vinod Roy, Leonidas Tsiokas, Sima Asfa, Prasanta Panja, Chinthalapally Rao, Stefan Wilhelm, Resham Bhattacharya, Priyabrata Mukherjee

ACS Nano· Volume 17· Issue 10

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Source abstract

Abstract

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.

Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Cell Adhesion Molecules Research · Extracellular vesicles in disease · Nanoplatforms for cancer theranostics

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States

Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States

Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma 73019, United States

Center for Cancer Prevention and Drug Development, Department of Medicine, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States

Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States

Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, United States

Funding

National Cancer Institute · Division of Chemical, Bioengineering, Environmental, and Transport Systems · National Institute of General Medical Sciences

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