Targeting KRAS Mutant Lung Cancer Cells with siRNA-Loaded Bovine Serum Albumin Nanoparticles
Open accessAbstract
Purpose KRAS is the most frequently mutated gene in human cancers. Despite its direct involvement in malignancy and intensive effort, direct inhibition of KRAS via pharmacological inhibitors has been challenging. RNAi induced knockdown using siRNAs against mutant KRAS alleles offers a promising tool for selective therapeutic silencing in KRAS-mutant lung cancers. However, the major bottleneck for clinical translation is the lack of efficient biocompatible siRNA carrier systems.Methods Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method to deliver siRNA targeting the KRAS G12S mutation. The BSA nanoparticles were characterized with respect to their size, zeta potential, encapsulation efficiency and nucleic acid release. Nanoparticle uptake, cellular distribution of nucleic acids, cytotoxicity and gene knock down to interfere with cancer hallmarks, uncontrolled proliferation and migration, were evaluated in KRAS G12S mutant A459 cells, a lung adenocarcinoma cell line.Results BSA nanoparticles loaded with siRNA resulted in nanoparticles smaller than 200 nm in diameter and negative zeta potentials, displaying optimal characteristics for in vivo application. Encapsulating and protecting the siRNA payload well, the nanoparticles enabled transport to A549 cells in vitro, could evade endosomal entrapment and mediated significant sequence-specific KRAS knockdown, resulting in reduced cell growth of siRNA transfected lung cancer cells.Conclusions BSA nanoparticles loaded with mutant specific siRNA are a promising therapeutic approach for KRAS-mutant cancers.
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Nanoparticle-based platforms delivering KRAS-specific siRNAs have been shown to reach cancer cells, decrease KRAS levels and produce anticancer activity.
“This technology has been shown to be adequately delivered to cancer cells and to effectively decrease their KRAS levels, resulting in anticancer activity200–202 (Table 1).”
From The current state of the art and future trends in RAS-targeted cancer therapies (2022) · cites this paper as [200]
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The current state of the art and future trends in RAS-targeted cancer therapies
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- Authors
- Mehta, A., Dalle Vedove, E., Isert, L., & Merkel, O. M.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Corresponding author
- Mehta, Aditi
- Merkel, Olivia M.
- Venue
- Pharmaceutical Research
- Published
- 2019-07-09
- Volume
- 36
- Issue
- 9
- Pages
- 133-133
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- PMC
- PMC7611029
- OpenAlex
- W2956241474
- Cited by
- 53
- References
- 37
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 9 · 2023: 10 · 2022: 7 · 2021: 6 · 2020: 7
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- European Research Council (ERC-2014-StG – 637830)
- Deutsche Gesellschaft für Muskelkranke (2017-Me7/1)
- Ludwig-Maximilians-Universität München (LMUexcellent Pilot Grant)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Keywords
- KRAS mutation, lung adenocarcinoma, siRNA delivery, bovine serum albumin nanoparticles, RNA interference, A549 cells, nanoparticle uptake, endosomal escape, gene knockdown, siRNA carriers
- MeSH terms
- A549 Cells, Animals, Cattle, Cell Survival, Humans, Lung Neoplasms, Mutation, Serum Albumin, Bovine, Transfection, Genetic Therapy, Proto-Oncogene Proteins p21(ras), Apoptosis, RNA, Small Interfering, Nanoparticles, Gene Knockdown Techniques
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