Versatile protamine nanocapsules to restore miR-145 levels and interfere tumor growth in colorectal cancer cells

Reimondez-Troitiño, Sonia; González-Aramúndiz, José Vicente; Ruíz-Bañobre, Juan; López‐López, Rafael; Alonso, María José; Csaba, Nœmi; Fuente, María de la

doi:10.1016/j.ejpb.2019.07.016

Cited by 22 publications

(12 citation statements)

References 53 publications

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“…From Figure S2, a band corresponding to free unbound miRNA after the incubation of SNs-ST (miR) with heparin can be observed. This indicated that the negatively charged molecule miRNA was at least partially displaced with high concentrations of the negatively charged heparin, indicating that an additional layer of protection, as for example, reported for protamine nanocapsules [17], could greatly improve their biological performance. A different strategy is the one reported in this work (see next section), with the encapsulation of the nucleic acids inside SNs previous complexation with cationic lipids (SNs-Lpx)…”

Section: Formulationsmentioning

confidence: 78%

“…Results evidenced again the superior performance of the formulation that encapsulates Lpx (SNs-Lpx), probably due to a protective effect of the miRNA145 ( Figure 4B). Importantly, results obtained with SNs-Lpx were superior to those recently published with miRNA145-loaded PLGA/PEI/HA nanoparticles in HTC-116 cells (11-fold increase), miRNA-145-loaded magnetic nanoparticles in AsPC-1cells (19-fold increase) and HPAF-II cells (4-fold increase), miRNA145-loaded cationic liposomes in HepG2 cells (9-fold increase), miRNA145 associated to a lentiviral vector in SW620 cells (8.2-fold increase), and miRNA145-loaded protamine nanocapsules in SW480 cells (33-fold increase) [15][16][17]49,50]. In relation to nanometric porous metal-organic frameworks (nanoMOFs), they show a similar efficiency in SW480 cells, superior to lipofectamine, as recently published by our group [51].…”

Section: Transfection Efficiencymentioning

confidence: 99%

“…However, the major barriers of miRNA delivery are (i) poor systemic stability, (ii) rapid clearance, (iii) degradation by nucleases, (iv) risk of systemic toxicity, (v) elimination by phagocytic immune cells, and (vi) lack of efficient delivery to targeted cells to achieve the desired therapeutic outcome [14]. For overcoming these constraints, different delivery systems have been proposed to date, such as PLGA/PEI/miRNA/HA nanoparticles, protamine nanoparticles, and magnetic nanoparticles [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

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Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics

et al. 2020

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Gene replacement therapy with oncosuppressor microRNAs (miRNAs) is a promising alternative to interfere with cancer progression. However, miRNAs are highly inefficient in a biological environment, hampering a successful translation to clinics. Nanotechnology can tackle this drawback by providing delivery systems able to efficiently deliver them to cancer cells. Thus, the objective of this work was to develop biocompatible nanosystems based on sphingomyelin (SM) for the intracellular delivery of miRNAs to colorectal cancer cells. We pursued two different approaches to select the most appropriate composition for miRNA delivery. On the one hand, we prepared sphingomyelin-based nanosystems (SNs) that incorporate the cationic lipid stearylamine (ST) to support the association of miRNA by the establishment of electrostatic interactions (SNs–ST). On the other hand, the cationic surfactant (DOTAP) was used to preform lipidic complexes with miRNA (Lpx), which were further encapsulated into SNs (SNs-Lpx). Restitution of miRNA145 levels after transfection with SNs-Lpx was related to the strongest anticancer effect in terms of tumor proliferation, colony forming, and migration capacity assays. Altogether, our results suggest that SNs have the potential for miRNA delivery to develop innovative anticancer therapies.

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Section: Formulationsmentioning

confidence: 78%

Section: Transfection Efficiencymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics

et al. 2020

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“…In our research group, alternative nanocarriers for the delivery of polynucleotides have already been explored. Based on the known capacity of cell penetrating peptides (CPPs) to efficiently condense nucleic acids and facilitate their transport across biological barriers ( 37 ), we have developed polyarginine- (pArg) and protamine-based nanosystems, which have shown the capacity to efficiently deliver different polynucleotides ( 38 – 40 ). Indeed, we have recently reported the formation of nanocomplexes of polynucleotides with cationic molecules, and their posterior envelopment with an hydrophilic anionic polymer, named as enveloped nanocomplexes (ENCPs), as a way to facilitate the delivery of miRNA to the brain ( 40 ).…”

Section: Introductionmentioning

confidence: 99%

Arginine-Based Poly(I:C)-Loaded Nanocomplexes for the Polarization of Macrophages Toward M1-Antitumoral Effectors

et al. 2020

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Tumor-associated macrophages (TAMs), with M2-like immunosuppressive profiles, are key players in the development and dissemination of tumors. Hence, the induction of M1 pro-inflammatory and anti-tumoral states is critical to fight against cancer cells. The activation of the endosomal toll-like receptor 3 by its agonist poly(I:C) has shown to efficiently drive this polarization process. Unfortunately, poly(I:C) presents significant systemic toxicity, and its clinical use is restricted to a local administration. Therefore, the objective of this work has been to facilitate the delivery of poly(I:C) to macrophages through the use of nanotechnology, that will ultimately drive their phenotype toward pro-inflammatory states. Methods: Poly(I:C) was complexed to arginine-rich polypeptides, and then further enveloped with an anionic polymeric layer either by film hydration or incubation. Physicochemical characterization of the nanocomplexes was conducted by dynamic light scattering and transmission electron microscopy, and poly(I:C) association efficiency by gel electrophoresis. Primary human-derived macrophages were used as relevant in vitro cell model. Alamar Blue assay, ELISA, PCR and flow cytometry were used to determine macrophage viability, polarization, chemokine secretion and uptake of nanocomplexes. The cytotoxic activity of pre-treated macrophages against PANC-1 cancer cells was assessed by flow cytometry. Results: The final poly(I:C) nanocomplexes presented sizes lower than 200 nm, with surface charges ranging from +40 to −20 mV, depending on the envelopment. They all presented high poly(I:C) loading values, from 12 to 50%, and great stability in cell culture media. In vitro, poly(I:C) nanocomplexes were highly taken up by macrophages, in comparison to the free molecule. Macrophage treatment with these nanocomplexes did not reduce their viability and efficiently stimulated the secretion of the T-cell recruiter chemokines CXCL10 and CCL5, of great importance for an effective anti-tumor immune response. Finally, poly(I:C) nanocomplexes significantly increased the ability of treated macrophages to directly kill cancer cells. Dacoba et al. Poly(I:C) Nanocomplexes for Macrophage M1-Polarization Conclusion: Overall, these enveloped poly(I:C) nanocomplexes might represent a therapeutic option to fight cancer through the induction of cytotoxic M1-polarized macrophages.

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“…In this study, CircInteractome was used to predict the potential miRNAs binding to circ-PRMT5, and miR-145 and miR-1304 were found to be the best prospective candidates. MiR-145 has been reported as a tumour suppressor in many cancer types, such as colorectal cancer [24], cervical carcinoma [25], prostate cancer [26], oesophageal squamous cell carcinoma [27] and gastric cancer [28]. MiR-1304 has also been reported being sponged by circRNAs to promote cancer progression [29,30].…”

Section: Discussionmentioning

confidence: 99%

Circ-PRMT5 promotes gastric cancer progression by sponging miR-145 and miR-1304 to upregulate MYC

Wei

Ding

Guo

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Background: Gastric cancer (GC) is a global leading source of cancer-associated deaths. Circular RNAs (circRNAs) are a new type of non-coding RNA and promising biomarkers for diagnosis of multiple diseases such as cancer. Methods: Circ-PRMT5 expression was validated in 90 GC patient tissues and 6 different GC cells by qRT-PCR. Sublocalization of circ-PRMT5 in GC cells was determined in isolated nuclear and cytoplasmic RNAs. CircInteractome and miRanda were used to predict binding sites between circ-PRMT5 with micRNAs, and micRNAs with target mRNA. The correlation between genes was determined by the Pearson correlation analysis. The molecular mechanism was demonstrated by RNA in vivo precipitation, point mutation, luciferase activity and rescue experiments. Results: Circ-PRMT5 expression was significantly higher in GC than in adjacent normal tissues, and GC patients with circ-PRMT5 high expression had shorter survival times. Functionally, circ-PRMT5 silence inhibited GC cell growth and invasion. Mechanism analysis showed that circ-PRMT5 sponged miR-145/ miR-1304 to upregulate MYC expression and GC development. Conclusion: Our findings demonstrated that circ-PRMT5 function as an oncogene in GC patients by targeting miR-145/miR-1304/MYC axis. High circ-PRMT5 expression may provide a poor prognostic indicator of survival in GC patients and targeting circ-PRMT5/miR-145/miR-1304/MYC axis may be a novel therapeutic strategy for GC.

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Versatile protamine nanocapsules to restore miR-145 levels and interfere tumor growth in colorectal cancer cells

Cited by 22 publications

References 53 publications

Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics

Sphingomyelin-Based Nanosystems (SNs) for the Development of Anticancer miRNA Therapeutics

Arginine-Based Poly(I:C)-Loaded Nanocomplexes for the Polarization of Macrophages Toward M1-Antitumoral Effectors

Circ-PRMT5 promotes gastric cancer progression by sponging miR-145 and miR-1304 to upregulate MYC

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