ArticleJournal of controlled release : official journal of the Controlled Release Society2013
Just getting into cells is not enough: mechanisms underlying 4-(N)-stearoyl gemcitabine solid lipid nanoparticle's ability to overcome gemcitabine resistance caused by RRM1 overexpression.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 49 citations in OpenAlex.
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- Solid lipid nanoparticles in pancreatic cancer treatment.BJC reports · 2025Review
- Improved Antitumor Efficiency ofInternational journal of nanomedicine · 2024Article
- Biological evaluation of novel gemcitabine analog in patient-derived xenograft models of pancreatic cancer.BMC cancer · 2023Article
- Synthesis, characterization, and anticancer evaluation of 1,3-bistetrahydrofuran-2yl-5-FU as a potential agent for pancreatic cancer.BMC cancer · 2022Article
- Nucleoside transporters and immunosuppressive adenosine signaling in the tumor microenvironment: Potential therapeutic opportunities.Pharmacology & therapeutics · 2022Review
- Effect of surface mannosylation on the cytotoxicity and cellular uptake of stearoyl gemcitabine-incorporated, acid-sensitive micelles.Colloid and interface science communications · 2021Article
- Endocytic Uptake of Solid Lipid Nanoparticles by the Nasal Mucosa.Pharmaceutics · 2021Article
- Enhancing efficacy of gemcitabine in pancreatic patient-derived xenograft mouse models.International journal of pharmaceutics: X · 2020Article
- Attempts to remodel the pathways of gemcitabine metabolism: Recent approaches to overcoming tumours with acquired chemoresistance.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Development and in-vitro characterization of nanoemulsions loaded with paclitaxel/γ-tocotrienol lipid conjugates.International journal of pharmaceutics · 2018Article
- Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles.International journal of nanomedicine · 2018Review
- Oral 4-(Oncotarget · 2017Article
- Lipid-Drug Conjugate for Enhancing Drug Delivery.Molecular pharmaceutics · 2017Review
- Synthesis, Characterization, and In Vitro and In Vivo Evaluations of 4-(N)-Docosahexaenoyl 2', 2'-Difluorodeoxycytidine with Potent and Broad-Spectrum Antitumor Activity.Neoplasia (New York, N.Y.) · 2016Article
- Solid Lipid Nanoparticles as Efficient Drug and Gene Delivery Systems: Recent Breakthroughs.Advanced pharmaceutical bulletin · 2015Review
- [Role of RRM1 in the Treatment and Prognosis of Advanced Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2015Review
- Potential applications of nanotechnology for the diagnosis and treatment of pancreatic cancer.Frontiers in physiology · 2014Review
- The effect of the acid-sensitivity of 4-(N)-stearoyl gemcitabine-loaded micelles on drug resistance caused by RRM1 overexpression.Biomaterials · 2013Article
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7 authors at 2 institutions in 1 country.
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Abstract
Gemcitabine is a deoxycytidine analog that is widely used in the chemotherapy of many solid tumors. However, acquired tumor cell resistance often limits its use. Previously, we discovered that 4-(N)-stearoyl gemcitabine solid lipid nanoparticles (4-(N)-GemC18-SLNs) can overcome multiple acquired gemcitabine resistance mechanisms, including RRM1 overexpression. The present study was designed to elucidate the mechanisms underlying the 4-(N)-GemC18-SLNs' ability to overcome gemcitabine resistance. The 4-(N)-GemC18 in the 4-(N)-GemC18-SLNs entered tumor cells due to clathrin-mediated endocytosis of the 4-(N)-GemC18-SLNs into the lysosomes of the cells, whereas the 4-(N)-GemC18 alone in solution entered cells by diffusion. We substantiated that it is the way the 4-(N)-GemC18-SLNs deliver the 4-(N)-GemC18 into tumor cells that allows the gemcitabine hydrolyzed from the 4-(N)-GemC18 to be more efficiently converted into its active metabolite, gemcitabine triphosphate (dFdCTP), and thus more potent against gemcitabine-resistant tumor cells than 4-(N)-GemC18 or gemcitabine alone. Moreover, we also showed that the RRM1-overexpressing tumor cells were also cross-resistant to cytarabine, another nucleoside analog commonly used in cancer therapy, and 4-(N)-stearoyl cytarabine carried by solid lipid nanoparticles can also overcome the resistance. Therefore, formulating the long-chain fatty acid amide derivatives of nucleoside analogs into solid lipid nanoparticles may represent a platform technology to increase the antitumor activity of the nucleoside analogs and to overcome tumor cell resistance to them.
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