Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer

Ap, Dinis Ano Bom; Pc, da Costa Neves; Almeida, Carlos Eduardo Bonacossa de; Silva, Dı́lson; Missailidis, Sotiris

doi:10.3390/pharmaceutics11120684

Cited by 15 publications

(12 citation statements)

References 72 publications

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“…Many studies have demonstrated the efficacies of aptamer-siRNA chimeras as targeted delivery, anti-cancer, or anti-viral therapies. This includes studies against various cancers such as lung carcinoma, melanoma, breast, and lymphoma [58][59][60][61] as well as against HIV by targeting the cell surface markers such as CD4, C-C chemokine receptor type 5 (CCR5), and glycoprotein 120 (gp120) [34,[62][63][64]. Therefore, presenting the potential of this combination as a useful dual-functioning antiviral treatment against SARS-CoV-2.…”

Section: Aptamersmentioning

confidence: 99%

Aptamer-Mediated Antiviral Approaches for SARS-CoV-2

Tan¹,

Jeevanandam²,

Rodrigues³

et al. 2022

Front. Biosci. (Landmark Ed)

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2020 and 2021 were disastrous years across the world, with the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus as a pandemic, which continues to be a top global health issue. There are still many countries and regions struggling to fight coronavirus disease 2019 (COVID-19), and, with the emergence of the various variants of the virus, we are still far from considering this global pandemic over. In addition to having good diagnostic tools and a variety of vaccines with high efficacy, it is of utmost importance to develop effective antiviral drugs or therapies to battle COVID-19. Aptamers known as the next-generation targeting elements can offer promising opportunities in developing antiviral drugs against SARS-CoV-2. This is owing to their high specificity and affinity, making them ideal for targeting ligands and neutralizers to impede both, viral entry and replication or even further enhance the anti-infection effects in the infected host cells. Also, aptamers are extremely attractive as they can be rapidly synthesized and scalable with a lower production cost. This work provides in-depth discussions on the potential of aptamers in therapeutic applications, their mode of action, and current progress on the use of aptamer-based therapies against SARS-CoV-2 and other viruses. The article also discusses the limitations associated with aptamer-based SARS-CoV-2-antiviral therapy with several proposed ideas to resolve them. Lastly, theranostic applications of aptamer nanoformulated dendrimers against viral infections are discussed.

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Section: Aptamersmentioning

confidence: 99%

Aptamer-Mediated Antiviral Approaches for SARS-CoV-2

Tan¹,

Jeevanandam²,

Rodrigues³

et al. 2022

Front. Biosci. (Landmark Ed)

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“…The small interfering RNAs (siRNAs), are a promising approach for gene therapy, however their intracellular administration remains difficult. To date, a great variety of delivery system for siRNAs has been investigated such as lipids, polymers, aptamers and cell penetrating peptides (CPPs) [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. In this regard, CPPs appear as a new class of transporters, which increase intracellular uptake of biologically active molecules including siRNAs [ 45 ] ( Figure 2 ).…”

Section: Benefit Of Cpps Used As Vehicles In Oligonucleotides Delimentioning

confidence: 99%

Cell Penetrating Peptides Used in Delivery of Therapeutic Oligonucleotides Targeting Hepatitis B Virus

et al. 2020

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Peptide Nucleic Acid (PNAs) and small noncoding RNAs including small interfering RNAs (siRNAs) represent a new class of oligonucleotides considered as an alternative therapeutic strategy in the chronic hepatitis B treatment. Indeed, chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide, despite the availability of an effective prophylactic vaccine. Current therapeutic approaches approved for chronic HBV treatment are pegylated-interferon alpha (IFN)-α and nucleos(t)ide analogues (NAs). Both therapies do not completely eradicate viral infection and promote severe side effects. In this context, the development of new effective treatments is imperative. This review focuses on antiviral activity of both PNAs and siRNAs targeting hepatitis B virus. Thus, we briefly present our results on the ability of PNAs to decrease hepadnaviral replication in duck hepatitis B virus (DHBV) model. Interestingly, other oligonucleotides as siRNAs could significantly inhibit HBV antigen expression in transient replicative cell culture. Because the application of these oligonucleotides as new antiviral drugs has been hampered by their poor intracellular bioavailability, we also discuss the benefits of their coupling to different molecules such as the cell penetrating peptides (CPPs), which were used as vehicles to deliver therapeutic agents into the cells.

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“…Several nanomaterials have been used for siRNA delivery like lipid nanoparticles, polymer nanoparticles, exosomes, aptamers, and inorganic nanoparticles. , Cationic polyelectrolytes and lipids are without any doubt the most efficient in complexing siRNAs through their positive charges via electrostatic interactions. However, positive charges induce toxicological endpoints over a certain concentration, limiting the therapeutic outcome.…”

Section: Introductionmentioning

confidence: 99%

Self-Assembled Oleic Acid-Modified Polyallylamines for Improved siRNA Transfection Efficiency and Lower Cytotoxicity

Salvador

Andreozzi

Romero

et al. 2023

ACS Appl. Bio Mater.

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Small interference RNA (siRNA) is a tool for gene modulation, which can silence any gene involved in genetic disorders. The potential of this therapeutic tool is hampered by RNA instability in the blood stream and difficulties to reach the cytosol. Polyamine-based nanoparticles play an important role in gene delivery. Polyallylamine hydrochloride (PAH) is a polycation displaying primary amines that can be easily chemically modified to match the balance between cell viability and siRNA transfection. In this work, PAH has been covalently functionalized with oleic acid at different molar ratios by carbodiimide chemistry. The substituted polymers form polyplexes that keep positive surface charge and fully encapsulate siRNA. Oleic acid substitution improves cell viability in the pulmonary cell line A549. Moreover, 6 and 14% of oleic acid substitution show an improvement in siRNA transfection efficiency. CD47 is a ubiquitous protein which acts as “don’t eat me signal.” SIRPα protein of macrophages recognizes CD47, leading to tumor cell phagocytosis by macrophages. By knocking down CD47 with siRNA, cancer cells become vulnerable to be eliminated by the immune system. PAH–oleic acid substitutes show high efficacy in silencing the CD47 protein, making them a potential candidate for immunotherapy.

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Aptamers as Delivery Agents of siRNA and Chimeric Formulations for the Treatment of Cancer

Cited by 15 publications

References 72 publications

Aptamer-Mediated Antiviral Approaches for SARS-CoV-2

Aptamer-Mediated Antiviral Approaches for SARS-CoV-2

Cell Penetrating Peptides Used in Delivery of Therapeutic Oligonucleotides Targeting Hepatitis B Virus

Self-Assembled Oleic Acid-Modified Polyallylamines for Improved siRNA Transfection Efficiency and Lower Cytotoxicity

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