miRacle of microRNA-Driven Cancer Nanotherapeutics

Abstract

MicroRNAs (miRNAs) are non-protein-coding RNA molecules 20–25 nucleotides in length that can suppress the expression of genes involved in numerous physiological processes in cells. Accumulating evidence has shown that dysregulation of miRNA expression is related to the pathogenesis of various human diseases and cancers. Thus, stragegies involving either restoring the expression of tumor suppressor miRNAs or inhibiting overexpressed oncogenic miRNAs hold potential for targeted cancer therapies. However, delivery of miRNAs to tumor tissues is a challenging task. Recent advances in nanotechnology have enabled successful tumor-targeted delivery of miRNA therapeutics through newly designed nanoparticle-based carrier systems. As a result, miRNA therapeutics have entered human clinical trials with promising results, and they are expected to accelerate the transition of miRNAs from the bench to the bedside in the next decade. Here, we present recent perspectives and the newest developments, describing several engineered natural and synthetic novel miRNA nanocarrier formulations and their key in vivo applications and clinical trials.

Nano-drug delivery system for pancreatic cancer: A visualization and bibliometric analysis

“…Various methods have been proven to be able to achieve targeted inhibition of specific miRNAs ( Sun et al, 2015 ; Liang et al, 2016 ; Van Roosbroeck et al, 2017 ; De Cola et al, 2018 ). However, susceptibility to degradation by nucleases, low intracellular absorption rate due to an inherent negative charge and hydrophilic structure, and potential off-target effects limit the application of miRNAs ( Kara et al, 2022 ). MiRNA nanocarriers based on polymers, inorganic materials, and lipids have demonstrated their potential in the treatment of PC ( Arora et al, 2014 ; Gurbuz and Ozpolat, 2019 ; Gokita et al, 2020 ; Wu et al, 2020 ; Borchardt et al, 2022 ).…”

“…MiRNA nanocarriers based on polymers, inorganic materials, and lipids have demonstrated their potential in the treatment of PC ( Arora et al, 2014 ; Gurbuz and Ozpolat, 2019 ; Gokita et al, 2020 ; Wu et al, 2020 ; Borchardt et al, 2022 ). However, it is important to note that therapeutic miRNAs can also accumulate in healthy tissues due to interstitial fluid pressure and shearing stress promoting NPs extravasation, which may lead to their degradation ( Zhang et al, 2019a ), and cause toxic and other adverse reactions ( Kara et al, 2022 ). Effective delivery and cell uptake of siRNA are major challenges in therapeutic applications ( Wang et al, 2016 ; Arnold et al, 2017 ; Tan et al, 2022 ).…”

Anti-ROR1 CAR-T cells: Architecture and performance

“…This product contains a recombinant herpes simplex virus type 1; it has been approved for the treatment of malignant glioma in Japan, and it is currently under clinical development for the management of prostate cancer (phase II), malignant pleural mesothelioma (phase I), and recurrent olfactory neuroblastoma (phase I) (42). Anticancer approaches based on microRNAs (43)(44)(45)(46), TILs (47)(48)(49), and T-cells engineered to express a chimeric antigen receptor (CAR-T cells) against tumor antigens are other current alternatives for the treatment of cancer (50)(51)(52).…”

Salivary miRNA 18a-5p Expression Level in Oral Squamous Cell Carcinoma

“…MicroRNAs have been examined in numerous cancers as significant biomarkers which play a significant role in the genesis of tumors, tumor invasion, and distant metastasis 8 . Small non-coding RNA molecules known as microRNAs, which have 18 to 22 nucleotides, regulate the expression of genes by attaching to the 3' region of the UTR 9 . Their function in numerous crucial sub-cellular biological processes, including cell differentiation, proliferation, and metabolism, has been widely studied 10 .…”