Nanoparticle-Based Delivery of Tumor Suppressor microRNA for Cancer Therapy

O'Neill, Clodagh P; Dwyer, Róisín M.

doi:10.3390/cells9020521

Cited by 68 publications

(50 citation statements)

References 64 publications

(126 reference statements)

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“…There are several hurdles to overcome, specifically concerning efficacy and side effects. The most pressing issue is miRNA delivery, as researchers have struggled to get sufficient amounts of miRNA intratumorally [ 69 ]. While ineffective delivery remains a major obstacle, in vivo studies using miRNA as single agents have also been underwhelming [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

miR-708-5p enhances erlotinib/paclitaxel efficacy and overcomes chemoresistance in lung cancer cells

Monteleone

Lutz

2020

Oncotarget

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Section: Discussionmentioning

confidence: 99%

miR-708-5p enhances erlotinib/paclitaxel efficacy and overcomes chemoresistance in lung cancer cells

Monteleone

Lutz

2020

Oncotarget

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“…There are several hurdles to overcome, speci cally concerning e cacy and side effects. The most pressing issue is miRNA delivery, as researchers have struggled to get su cient amounts of miRNA intratumorally (77). While ineffective delivery remains a major obstacle, in vivo studies using miRNA as single agents have also been underwhelming (78).…”

Section: Discussionmentioning

confidence: 99%

miR-708-5p Enhances Erlotinib/paclitaxel Efficacy and Overcomes Chemoresistance in Lung Cancer Cells

Monteleone

Lutz

2020

Preprint

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BackgroundLung cancer is a collection of aggressive tumors generally not diagnosed until late-stage, resulting in high mortality rates. The vast majority of non-small cell lung cancer (NSCLC) patients undergo combinatory chemotherapeutic treatment, which initially reduces tumor growth, but frequently becomes ineffective due to toxicity and resistance. Researchers have identified multiple signaling pathways involved in lung cancer chemoresistance, including cyclooxygenase-2 (COX-2)/microsomal prostaglandin E synthase-1 (mPGES-1) derived prostaglandin E2 (PGE2). While COX-2 inhibitors have shown promise in the clinic, their use is limited due to severe side effects. One novel approach to effectively suppress COX-2 signaling is through microRNA (miRNA). MiRNAs are small-noncoding RNAs commonly misexpressed in cancer. One tumor suppressive miRNA, miR-708-5p, has been shown to repress pro-resistant signaling pathways, including COX-2 and mPGES-1. MethodsmiR-708-5p expression was measured via RT-qPCR, while protein expression was assessed using western blotting. Biological changes in lung cancer cell proliferation and survival were evaluated using Ki-67 and Annexin V staining via flow cytometry, respectively. ResultsHere, we demonstrate that chemotherapies reduce COX-2 expression, possibly through induction of miR-708-5p. Moreover, combination treatment of erlotinib (ERL) or paclitaxel (PAC) with miR-708-5p enhances COX-2 and mPGES-1 protein suppression. We also show that combination chemotherapeutic and miR-708-5p treatment intensifies the anti-proliferative and pro-apoptotic effects of ERL and PAC. We also created ERL and PAC resistant lung cancer cell lines, which have increased COX-2 expression and diminished miR-708-5p levels compared to naïve lung cancer cells. While ERL and PAC treatments do not alter resistant cell phenotype alone, combination treatment with miR-708-5p partially restores the chemotherapies’ anti-proliferative effects and fully restores their pro-apoptotic qualities. ConclusionThese data suggest miR-708-5p may have potential combinatory therapeutic value to more efficaciously treat lung tumors while overcoming chemoresistance.

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“…SiRNAs can be incorporated into an NP formulation through covalent bonds with the NP components or by electrostatic interactions with the NP surface, due to their strong negative charge. NP-based delivery systems can also be used to deliver shRNAs [15] or miRNAs [16]. However, this review focuses on recent advances in non-viral siRNA delivery systems, including lipid, polymer, and inorganic-based NPs aimed at delivering siRNAs to tumor cells or immune cells for cancer treatment and the induction of anti-tumor immune responses.…”

Section: Introductionmentioning

confidence: 99%

Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

2020

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RNA interference (RNAi) uses small interfering RNAs (siRNAs) to mediate gene-silencing in cells and represents an emerging strategy for cancer therapy. Successful RNAi-mediated gene silencing requires overcoming multiple physiological barriers to achieve efficient delivery of siRNAs into cells in vivo, including into tumor and/or host cells in the tumor micro-environment (TME). Consequently, lipid and polymer-based nanoparticle siRNA delivery systems have been developed to surmount these physiological barriers. In this article, we review the strategies that have been developed to facilitate siRNA survival in the circulatory system, siRNA movement from the blood into tissues and the TME, targeted siRNA delivery to the tumor or specific cell types, cellular uptake, and escape from endosomal degradation. We also discuss the use of various types of lipid and polymer-based carriers for cancer therapy, including a section on anti-tumor nanovaccines enhanced by siRNAs. Finally, we review current and recent clinical trials using NPs loaded with siRNAs for cancer therapy. The siRNA cancer therapeutics field is rapidly evolving, and it is conceivable that precision cancer therapy could, in the relatively near future, benefit from the combined use of cancer therapies, for example immune checkpoint blockade together with gene-targeting siRNAs, personalized for enhancing and fine-tuning a patient’s therapeutic response.

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Nanoparticle-Based Delivery of Tumor Suppressor microRNA for Cancer Therapy

Cited by 68 publications

References 64 publications

miR-708-5p enhances erlotinib/paclitaxel efficacy and overcomes chemoresistance in lung cancer cells

miR-708-5p enhances erlotinib/paclitaxel efficacy and overcomes chemoresistance in lung cancer cells

miR-708-5p Enhances Erlotinib/paclitaxel Efficacy and Overcomes Chemoresistance in Lung Cancer Cells

Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy

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