Aptamer-guided siRNA-loaded nanomedicines for systemic gene silencing in CD-44 expressing murine triple-negative breast cancer model

Alshaer, Walhan; Hillaireau, Hervé; Vergnaud-Gauduchon, Juliette; Mura, Simona; Deloménie, Claudine; Sauvage, Félix; Ismail, Said I.; Fattal, Elias

doi:10.1016/j.jconrel.2017.12.022

Cited by 109 publications

(67 citation statements)

References 45 publications

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“…He et al have reported aptamer-drug conjugate (ApDC), AS1411-triptolide conjugate (ATC) for TNBC therapeutics with higher efficacies [148]. Nanomedicine is advancing rapidly, and now researchers have focused on combining all the technologies mentioned above (siRNA, miRNA, aptamers) by loading them into nanoparticles that pursue the CD-44 receptor characteristic of TNBC pluripotent cells [149].…”

Section: Aptamersmentioning

confidence: 99%

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

Medina

Oza

Sharma

et al. 2020

IJERPH

211

164

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Triple-negative breast cancer (TNBC) cells are deficient in estrogen, progesterone and ERBB2 receptor expression, presenting a particularly challenging therapeutic target due to their highly invasive nature and relatively low response to therapeutics. There is an absence of specific treatment strategies for this tumor subgroup, and hence TNBC is managed with conventional therapeutics, often leading to systemic relapse. In terms of histology and transcription profile these cancers have similarities to BRCA-1-linked breast cancers, and it is hypothesized that BRCA1 pathway is non-functional in this type of breast cancer. In this review article, we discuss the different receptors expressed by TNBC as well as the diversity of different signaling pathways targeted by TNBC therapeutics, for example, Notch, Hedgehog, Wnt/b-Catenin as well as TGF-beta signaling pathways. Additionally, many epidermal growth factor receptor (EGFR), poly (ADP-ribose) polymerase (PARP) and mammalian target of rapamycin (mTOR) inhibitors effectively inhibit the TNBCs, but they face challenges of either resistance to drugs or relapse. The resistance of TNBC to conventional therapeutic agents has helped in the advancement of advanced TNBC therapeutic approaches including hyperthermia, photodynamic therapy, as well as nanomedicine-based targeted therapeutics of drugs, miRNA, siRNA, and aptamers, which will also be discussed. Artificial intelligence is another tool that is presented to enhance the diagnosis of TNBC.

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Section: Aptamersmentioning

confidence: 99%

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

Medina

Oza

Sharma

et al. 2020

IJERPH

211

164

View full text Add to dashboard Cite

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“…However, they suffer from relatively low loading capacity for siRNA and premature leakage of payloads, and they require additional cationic materials to condense the highly anionic payloads into the liposomal core. Commonly used condensers include protamine, peptides, and polyethylenimine (PEI) …”

Section: Protective Carriers For Sirna Deliverymentioning

confidence: 99%

“…However, in other (non‐tumor) animal disease models, the use of selective homing agents can generate more substantial accumulation of siRNA . For applications beyond local administration and passive MPS‐mediated homing to clearance organs (e.g., liver, lungs, spleen), the literature contains a wide variety of homing moieties that can be decorated on the surface of carrier particles for in vivo targeting, including aptamers and receptor‐specific ligands . But currently peptides and antibodies have been the most widely used targeting agents.…”

Section: Selective Tissue Targetingmentioning

confidence: 99%

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

2019

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201903637.With the recent FDA approval of the first siRNA-derived therapeutic, RNA interference (RNAi)-mediated gene therapy is undergoing a transition from research to the clinical space. The primary obstacle to realization of RNAi therapy has been the delivery of oligonucleotide payloads. Therefore, the main aims is to identify and describe key design features needed for nanoscale vehicles to achieve effective delivery of siRNA-mediated gene silencing agents in vivo. The problem is broken into three elements: 1) protection of siRNA from degradation and clearance; 2) selective homing to target cell types; and 3) cytoplasmic release of the siRNA payload by escaping or bypassing endocytic uptake. The in vitro and in vivo gene silencing efficiency values that have been reported in publications over the past decade are quantitatively summarized by material type (lipid, polymer, metal, mesoporous silica, and porous silicon), and the overall trends in research publication and in clinical translation are discussed to reflect on the direction of the RNAi therapeutics field.

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“…These Apt1-functionalized liposomes showed higher selectivity and uptake by CD44+ cancer cell lines compared to the CD44− cell line [198]. Moreover, thiolated Apt1 conjugation with DSPE-PEG-maleimide using thiol-maleimide chemistry followed by successful post-insertion into liposomes was done by Alshaer et al [199]. Micelles composed of DSPE-PEG and DSPE-PEG-maleimide were prepared by the thin film evaporation hydration method.…”

Section: Thiol Maleiimide and Related Chemistrymentioning

confidence: 99%

“…Conjugation of Apt1-SH to micelle-DSPE-PEG-mal was performed using a thiol-maleimide cross-linking reaction to form a thioether bond. Then, the micelle-DSPE-PEG-Apt1 was post-inserted in siRNA-loaded liposomes by mixing and incubating at 60 • C for 1 h. Such nanocarriers showed a higher luc2 inhibition by Apt1-functionalized liposomes in vitro and a prolonged gene inhibition in vivo on an orthotopic MDA-MB-231 breast cancer model [199]. The same thiol-maleimide post-insertion protocol was also adapted with AS1411-functionalized thermosensitive liposomes encapsulating both doxorubicin and ammonium bicarbonate, for the selective targeting of multidrug-resistant breast cancer cells (MCF-7/MDR) that overexpress nucleolin [200].…”

Section: Thiol Maleiimide and Related Chemistrymentioning

confidence: 99%

Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

et al. 2019

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Soon after they were first described in 1990, aptamers were largely recognized as a new class of biological ligands that can rival antibodies in various analytical, diagnostic, and therapeutic applications. Aptamers are short single-stranded RNA or DNA oligonucleotides capable of folding into complex 3D structures, enabling them to bind to a large variety of targets ranging from small ions to an entire organism. Their high binding specificity and affinity make them comparable to antibodies, but they are superior regarding a longer shelf life, simple production and chemical modification, in addition to low toxicity and immunogenicity. In the past three decades, aptamers have been used in a plethora of therapeutics and drug delivery systems that involve innovative delivery mechanisms and carrying various types of drug cargos. However, the successful translation of aptamer research from bench to bedside has been challenged by several limitations that slow down the realization of promising aptamer applications as therapeutics at the clinical level. The main limitations include the susceptibility to degradation by nucleases, fast renal clearance, low thermal stability, and the limited functional group diversity. The solution to overcome such limitations lies in the chemistry of aptamers. The current review will focus on the recent arts of aptamer chemistry that have been evolved to refine the pharmacological properties of aptamers. Moreover, this review will analyze the advantages and disadvantages of such chemical modifications and how they impact the pharmacological properties of aptamers. Finally, this review will summarize the conjugation strategies of aptamers to nanocarriers for developing targeted drug delivery systems. Molecules 2020, 25, 3 2 of 51 molecules [2]. Nowadays, the aptamer field covers various biomedical applications, including [3], therapeutic [4-6], aptasensors [7], biosensors [8,9], diagnostic [10,11], and imaging systems [12].Aptamers need to be stabilized for in vivo use against nuclease degradation, and their small size makes them susceptible to renal filtration. Aptamers' stabilization can be attained by chemically modifying them using different approaches. Moreover, introducing chemical modifications into nucleic acid libraries increases the interaction capabilities of aptamers and thereby their target spectrum [12]. Modified aptamers may show improved chemical diversity relative to aptamers composed entirely of natural DNA or RNA nucleotides and expand their applications in diagnostics, therapeutics, and nanotechnology [1].Chemical modifications of aptamer oligonucleotides are needed mainly to enhance their resistance to nuclease degradation and lowering their renal filtration. Additionally, chemical modifications, in some cases, may increase the aptamer-binding affinity [13]. Many approaches have been introduced to promote the stability of aptamers without altering their binding affinity and specificity against their targets. These approaches include chemical modification of the phosphate...

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Aptamer-guided siRNA-loaded nanomedicines for systemic gene silencing in CD-44 expressing murine triple-negative breast cancer model

Cited by 109 publications

References 45 publications

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

Aptamers Chemistry: Chemical Modifications and Conjugation Strategies

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