ArticleMolecular pharmaceutics2011
Paclitaxel tumor-priming enhances siRNA delivery and transfection in 3-dimensional tumor cultures.
Article in Molecular pharmaceutics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 42 citations in OpenAlex.
- Cancer nanomedicine in preoperative therapeutics: Nanotechnology-enabled neoadjuvant chemotherapy, radiotherapy, immunotherapy, and phototherapy.Bioactive materials · 2023Review
- Nanoparticle-Based Combination Therapy for Ovarian Cancer.International journal of nanomedicine · 2023Review
- Nanocarrier-based drug combination therapy for glioblastoma.Theranostics · 2020Review
- SiRNA-MediatedInternational journal of medical sciences · 2019Article
- A biodistribution study of solid lipid-polyethyleneimine hybrid nanocarrier for cancer RNAi therapy.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2016Article
- Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
- Delivery of cancer therapeutics to extracellular and intracellular targets: Determinants, barriers, challenges and opportunities.Advanced drug delivery reviews · 2016Review
- Paclitaxel tumor priming promotes delivery and transfection of intravenous lipid-siRNA in pancreatic tumors.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Tumor priming enhances siRNA delivery and transfection in intraperitoneal tumors.Journal of controlled release : official journal of the Controlled Release Society · 2014Article
- Hypoxia-targeted siRNA delivery.Angewandte Chemie (International ed. in English) · 2014Article
- Photoswitchable nanoparticles for in vivo cancer chemotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Cancer cell spheroids as a model to evaluate chemotherapy protocols.Cancer biology & therapy · 2012Article
- Advances in the formation, use and understanding of multi-cellular spheroids.Expert opinion on biological therapy · 2012Review
- Improving delivery and efficacy of nanomedicines in solid tumors: role of tumor priming.Nanomedicine (London, England) · 2011Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The clinical development of siRNA cancer therapeutics is limited by the poor interstitial transport and inefficient transfection in solid tumors. We have shown that paclitaxel pretreatment, by inducing apoptosis, causes expansion of the interstitial space and thereby improves nanoparticle delivery and transport in tumor interstitium (referred to as paclitaxel tumor priming) and efficacy of nanomedicines in tumor-bearing animals. The present study evaluated whether paclitaxel tumor priming improves the delivery and transfection of siRNA in 2- and 3-dimensional cultures of human oropharyngeal carcinoma FaDu cells. We used the fluorescent siGLO and confocal microcopy to monitor transport, and used survivin siRNA and immunostaining and immunoblotting to monitor transfection. Survivin is a chemoresistance gene/protein, inducible by chemotherapy. siRNA was loaded in cationic liposomes. The results showed that pretreatment with 50-200 nM paclitaxel (24 or 48 h before siRNA) enhanced the total uptake of siGLO into monolayers (∼15%, p < 0.05), and the depth of penetration into 3-dimensional spheroids and tumor fragment histocultures (2.1- to 2.5-times greater area under the penetration-depth curve). In both monolayer cells and histocultures, paclitaxel pretreatment induced survivin upregulation (p < 0.05). Survivin siRNA alone decreased the survivin levels in a dose-dependent manner, and applying survivin siRNA after paclitaxel pretreatment completely abolished the paclitaxel-induced survivin increases. These findings indicate that paclitaxel tumor priming did not compromise the siRNA functionality. In summary, paclitaxel tumor priming improved the penetration, transfection and functionality of siRNA in tumors, thus offering a promising and practical means to develop chemo-siRNA cancer gene therapy.
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