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Pharmaceutics
Special Issues
Therapeutic RNA Delivery Systems for Treatment of Cancer
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Therapeutic RNA Delivery Systems for Treatment of Cancer

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Biopharmaceutics".

Deadline for manuscript submissions: closed (10 January 2024) | Viewed by 10369

Special Issue Editors

Dr. Claudia Conte

E-Mail Website
Guest Editor
Drug Delivery Laboratory, Department of Pharmacy, University of Napoli Federico II, 80131 Napoli, Italy
Interests: siRNA-based therapy; polymeric nanoparticles for cancer; combination therapies; drug delivery
Dr. Ernest Moles

E-Mail Website
Guest Editor
Translational Cancer NanoMedicine Program, Children’s Cancer Institute, Australian Centre for Nanomedicine, University of New South Wales (UNSW), Sydney, NSW, Australia
Interests: nanoparticle-assisted RNA delivery; cancer immunotherapy; RNA interference; drug delivery systems; systemic drug delivery
Dr. Zerong Ma

E-Mail Website
Guest Editor
Translational Cancer NanoMedicine Program, Children’s Cancer Institute, Australian Centre for Nanomedicine, University of New South Wales (UNSW), Sydney, NSW, Australia
Interests: nanoparticle-assisted RNA delivery; siRNA-based therapy; drug delivery systems; systemic and aerosol delivery

Special Issue Information

Dear Colleagues,

RNA therapeutics are changing the way we treat cancer. Adding to their cost-effective manufacturing, RNA drugs can be custom-engineered to silence specific cellular pathways necessary for the cancer cells to survive. Lipid-based and polymeric nanoparticle systems have been developed to protect the RNA and mediate its intracellular delivery. Recent advances in the synthesis of vitro-transcribed mRNA, accompanied by the development of novel nanoparticle carriers for its effective systemic delivery, have additionally marked a new era in cancer therapy, introducing new treatment strategies where immunostimulatory and/or cancer-suppressor proteins are expressed directly in vivo. Since 2018, the United States Food and Drug Administration (FDA) has approved four nanoparticle-assisted RNA interference drugs for the treatment of haepatic diseases (Patisiran, Givosiran, Lumasiran, Inclisiran) and two lipid nanoparticle-formulated mRNA vaccines for COVID-19 (BNT162b2, Spikevax), and similar RNA nanotherapeutics are in the clinical pipeline in the treatment of cancer.

This Special Issue aims to summarize the most recent advances in the nanoparticle-assisted delivery of RNA for the treatment of cancer. In addition to recent research on nanoparticle carriers for RNA interference therapy, novel immunotherapeutic strategies using nanoparticle-formulated mRNAs (e.g., immunomodulator expression, dendritic cell activation, and/or T cell reprogramming) will be discussed.

Dr. Claudia Conte
Dr. Ernest Moles
Dr. Zerong Ma
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • RNA therapy
  • cancer immunotherapy
  • lipid nanoparticles
  • mRNA vaccine delivery
  • RNA interference
  • nanoparticle-formulated mRNA
  • non-viral RNA delivery systems
  • systemic RNA delivery

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Published Papers (2 papers)

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19 pages, 4126 KiB  
Article
Effect of PEG Anchor and Serum on Lipid Nanoparticles: Development of a Nanoparticles Tracking Method
by Manon Berger, Manon Degey, Jeanne Leblond Chain, Erik Maquoi, Brigitte Evrard, Anna Lechanteur and Géraldine Piel
Pharmaceutics 2023, 15(2), 597; https://doi.org/10.3390/pharmaceutics15020597 - 10 Feb 2023
Cited by 28 | Viewed by 6246
Abstract
Polyethylene glycol (PEG) is used in Lipid Nanoparticles (LNPs) formulations to confer stealth properties and is traditionally anchored in membranes by a lipid moiety whose length significantly impacts the LNPs fate in vivo. C18 acyl chains are efficiently anchored in the membrane, while [...] Read more.
Polyethylene glycol (PEG) is used in Lipid Nanoparticles (LNPs) formulations to confer stealth properties and is traditionally anchored in membranes by a lipid moiety whose length significantly impacts the LNPs fate in vivo. C18 acyl chains are efficiently anchored in the membrane, while shorter C14 lipids are quickly desorbed and replaced by a protein corona responsible for the completely different fate of LNPs. In this context, a method to predict the biological behavior of LNPs depending on the lipid-PEG dissociation was developed using the Nanoparticle Tracking Analysis (NTA) method in serum. Two formulations of siRNA-containing LNPs were prepared including CSL3 or SM-102 lipids and were grafted with different lipids-PEG (C18, C14 lipids-PEG, and Ceramide-PEG). The impact of the lipid-PEG on the interactions between LNPs and serum components was demonstrated by monitoring the mean particle size and the concentration over time. In vitro, these formulations demonstrated low toxicity and efficient gene knockdown on tumor MDA-MB-231 cells, but serum was found to significantly impact the efficiency of C18-PEG-based LNPs, while it did not impact the efficiency of C14-PEG-based LNPs. The NTA method demonstrated the ability to discriminate between the behaviors of LNPs according to serum proteins’ interactions. CSL3 lipid and Cer-PEG were confirmed to have promise for LNP formulation. Full article
(This article belongs to the Special Issue Therapeutic RNA Delivery Systems for Treatment of Cancer)
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16 pages, 3425 KiB  
Article
Combination of Nanovectorized siRNA Directed against Survivin with Doxorubicin for Efficient Anti-Cancer Activity in HER2+ Breast Cancer Cells
by Sahar Eljack, Emilie Allard-Vannier, Yoann Misericordia, Katel Hervé-Aubert, Nicolas Aubrey, Igor Chourpa, Areeg Faggad and Stephanie David
Pharmaceutics 2022, 14(11), 2537; https://doi.org/10.3390/pharmaceutics14112537 - 21 Nov 2022
Cited by 11 | Viewed by 2976
Abstract
According to Globocan 2020, breast cancer is considered one of the most common cancers affecting women and is one of the leading causes of death in over 100 countries. The available classical treatment options do not always give satisfactory outcomes, and some patients [...] Read more.
According to Globocan 2020, breast cancer is considered one of the most common cancers affecting women and is one of the leading causes of death in over 100 countries. The available classical treatment options do not always give satisfactory outcomes, and some patients develop resistance to these treatments. This study aims to investigate the combination of nanovectorized siRNA directed against anti-apoptotic protein Survivin (siSurvivin) by targeted stealth magnetic siRNA nanovectors (TS-MSN), designed in our lab, with Doxorubicin (DOX), as an option for HER2+ breast cancer treatment. The hypothesis is that the pretreatment of the HER2+ breast cancer cell line SK-BR-3 with siSurvivin will induce apoptosis in the cancer cells and enhance the therapeutic efficacy of DOX, allowing a dose reduction of DOX and hence a reduction of potential side effects. TS-MSN are based on superparamagnetic iron oxide nanoparticles (SPIONs) covalently coupled with a fluorophore sulfocyanine-5 and polyethylene glycol 5000 (PEG5000) and functionalized with single-chain variable fragments (scFv) of an antibody targeting the HER2 membrane receptor. These covalently functionalized SPIONs are then complexed via electrostatic interactions with therapeutic siRNA and the cationic polymers, chitosan, and poly-L-arginine. TS-MSNsiSurvivin had an average size of 144 ± 30 nm, a PDI of 0.3, and a slightly positive zeta potential value of 10.56 ± 05.70 mV. The agarose gel electrophoresis assay confirmed that the siRNA is well-complexed into TS-MSN without leakage, as no free siRNA was detected. Moreover, siRNA in TS-MSN was protected from RNAse A degradation for up to 6 h at 37 °C. Formulations of TS-MSN with siSurvivin demonstrated in vitro gene knockdown up to 89% in the HER2+ breast cancer cell line SK-BR-3. Furthermore, qRT-PCR confirmed a significant Survivin mRNA relative expression inhibition (about 50%) compared to control siRNA or untreated cells. A combination protocol was evaluated between TS-MSN and Doxorubicin (DOX) for the first time. Therefore, SK-BR-3 cells were pretreated with TS-MSN formulated with siSurvivin at 50 nM for 24 h alone, before a DOX treatment at a concentration of 0.5 µM (corresponding to the IC50) was added for 48 h. The MTT cytotoxicity tests, performed after 72 h of treatment, revealed that the combination had a significant synergistic cytotoxic effect on SK-BR-3 cells compared to monotherapies or untreated cells. We confirmed that pretreatment of cells with siSurvivin potentializes the cytotoxic effect of DOX as an alternative approach for treating HER2+ breast cancer. In conclusion, a combination of anti-Survivin siRNA and DOX would be a good alternative in HER2+ breast cancer therapy. Full article
(This article belongs to the Special Issue Therapeutic RNA Delivery Systems for Treatment of Cancer)
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