Perspectives of using microRNA-loaded nanocarriers for epigenetic reprogramming of drug resistant colorectal cancers

Olga A Sukocheva; Junqi Liu; Margarita E Neganova; Narasimha M Beeraka; Yulia R Aleksandrova; Prasath Manogaran; Ekaterina M Grigorevskikh; Vladimir N Chubarev; Ruitai Fan

doi:10.1016/j.semcancer.2022.05.012

Perspectives of using microRNA-loaded nanocarriers for epigenetic reprogramming of drug resistant colorectal cancers

Semin Cancer Biol. 2022 Nov;86(Pt 2):358-375. doi: 10.1016/j.semcancer.2022.05.012. Epub 2022 May 24.

Authors

Olga A Sukocheva¹, Junqi Liu², Margarita E Neganova³, Narasimha M Beeraka⁴, Yulia R Aleksandrova³, Prasath Manogaran⁵, Ekaterina M Grigorevskikh⁶, Vladimir N Chubarev⁶, Ruitai Fan⁷

Affiliations

¹ Cancer Center and Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou 450052, China; The National Centre for Neuroimmunology and Emerging Diseases, Menzies Health Institute, Griffith University, Queensland, Australia; Discipline of Health Sciences, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA 5042, Australia. Electronic address: olga.sukocheva@flinders.edu.au.
² Cancer Center and Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou 450052, China.
³ Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1, Severnii pr., Chernogolovka 142432, Russia.
⁴ Cancer Center and Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou 450052, China; Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Street, Moscow 119991, Russia; Center of Excellence in Molecular Biology and Regenerative Medicine (CEMR), Department of Biochemistry, JSS Academy of Higher Education and Research (JSS AHER), JSS Medical College, Mysuru, Karnataka, India.
⁵ Translational Research Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu 641046, India.
⁶ Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8/2 Trubetskaya Street, Moscow 119991, Russia.
⁷ Cancer Center and Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshedong Str., Zhengzhou 450052, China. Electronic address: fccfanrt@zzu.edu.cn.

PMID: 35623562
DOI: 10.1016/j.semcancer.2022.05.012

Abstract

Epigenetic regulation by microRNAs (miRs) demonstrated a promising therapeutic potential of these molecules to regulate genetic activity in different cancers, including colorectal cancers (CRCs). The RNA-based therapy does not change genetic codes in tumor cells but can silence oncogenes and/or reactivate inhibited tumor suppressor genes. In many cancers, specific miRs were shown to promote or stop tumor progression. Among confirmed and powerful epigenetic regulators of colon carcinogenesis and development of resistance are onco-miRs, which include let-7, miR-21, miR-22, miR-23a, miR-27a, miR-34, miR-92, miR-96, miR-125b, miR-135b, miR-182, miR-200c, miR-203, miR-221, miR-421, miR-451, and others. Moreover, various tumor-suppressor miRs (miR-15b-5b, miR-18a, miR-20b, miR-22, miR-96, miR-139-5p, miR-145, miR-149, miR-197, miR-199b, miR-203, miR-214, miR-218, miR-320, miR-375-3p, miR-409-3p, miR-450b-5p, miR-494, miR-577, miR-874, and others) were found silenced in drug-resistant CRCs. Re-expression of tumor suppressor miR is complicated by the chemical nature of miRs that are not long-lasting compounds and require protection from the enzymatic degradation. Several recent studies explored application of miRs using nanocarrier complexes. This study critically describes the most successfully tested nanoparticle complexes used for intracellular delivery of nuclear acids and miRs, including micelles, liposomes, inorganic and polymeric NPs, dendrimers, and aptamers. Nanocarriers shield incorporated miRs and improve the agent stability in circulation. Attachment of antibodies and/or specific peptide or ligands facilitates cell-targeted miR delivery. Addressing in vivo challenges, a broad spectrum of non-toxic materials has been tested and indicated reliable advantages of lipid-based (lipoplexes) and polymer-based liposomes. Recent cutting-edge developments indicated that lipid-based complexes with multiple cargo, including several miRs, are the most effective approach to eradicate drug-resistant tumors. Focusing on CRC-specific miRs, this review provides a guidance and insights towards the most promising direction to achieve dramatic reduction in tumor growth and metastasis using miR-nanocarrier complexes.

Keywords: Cancer; Epigenetics; Lipoplexes; MicroRNAs; Nanocarriers; Nanoparticles.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Colorectal Neoplasms* / drug therapy
Colorectal Neoplasms* / genetics
Colorectal Neoplasms* / metabolism
Epigenesis, Genetic
Humans
Lipids
Liposomes / chemistry
MicroRNAs* / genetics

Substances

Lipids
Liposomes
MicroRNAs
MIRN139 microRNA, human
MIRN145 microRNA, human
MIRN149 microRNA, human
MIRN203 microRNA, human
MIRN214 microRNA, human
MIRN218 microRNA, human
MIRN421 microRNA, human
MIRN577 microRNA, human
MIRN874 microRNA, human