Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 28:3:100103.
doi: 10.1016/j.crphar.2022.100103. eCollection 2022.

New paradigm in combination therapy of siRNA with chemotherapeutic drugs for effective cancer therapy

Affiliations
Review

New paradigm in combination therapy of siRNA with chemotherapeutic drugs for effective cancer therapy

Krishan Kumar et al. Curr Res Pharmacol Drug Discov. .

Abstract

Chemotherapeutics drugs play a pivotal role in the treatment of cancer. However, many issues generate by chemotherapy drugs, including unfavorable harm to healthy cells and multidrug resistance (MDR), persist and have a negative impact on therapeutic outcomes. When compared to monotherapy, combination cancer therapy has many advantages, like improving efficacy through synergistic effects and overcoming drug resistance. Combination treatment may comprise several chemotherapeutics drugs and combinations of chemotherapeutic drugs with some other therapeutic options such as surgery or radiation. Cancer treatment that utilizes co-delivery strategies with siRNA and chemotherapeutic drugs has been shown to have highly effective antitumor effects in the treatment of many cancers. However, the highly complex mechanisms of chemotherapeutic drugs-siRNA pairs during the co-delivery process have received little attention. The ideal combination of chemotherapeutic drugs with siRNA is very crucial for producing the desirable anticancer effects that would greatly enhance therapeutic efficiency. This review puts an emphasis on the logic for choosing suitable chemotherapeutic drug-siRNA combinations, which may open the way for the co-delivery of chemotherapeutic drugs and siRNA for treating cancer in the clinic. This review summarizes recent breakthrough in the area of diverse mechanism-based chemotherapeutic drugs-siRNA combinations in cancer treatment.

Keywords: Apoptosis; Cancer treatment; Chemotherapeutic drug; Combination therapy; Gene silencing; Multidrug resistance; RNA interference; siRNA.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships, which have, or could be perceived to have, influenced the work reported in this article.

Figures

Image 1
Graphical abstract
Fig. 1
Fig. 1
Process of siRNA mediated RNA interference: The siRNA pathway starts with the Dicer enzyme complex cleaving long double-stranded RNA (dsRNA) into siRNA or introducing exogenous siRNA into the cytoplasm. Then siRNAs are bound to Argonaute 2 (AGO2) and the RNA-induced silencing complex (RISC). If the RNA duplex packed onto RISC has an ideal complementarity sequence, AGO2 cleaves the passenger (sense) strand, resulting in active RISC containing the guide (antisense) strand. The siRNA guide strand detects target sites for direct mRNA cleavage (brought out via catalytic domain of AGO2), which results in translation inhibition that further blocks protein synthesis (de Fougerolles et al., 2007).
Fig. 2
Fig. 2
Advantages of combination therapy of siRNA with chemotherapeutic drug for safe and targeted treatment of cancer.
Fig. 3
Fig. 3
Extracellular barriers to RNAi mediated siRNA therapy (A) Enzymatic degradation: Endonuclease degrades siRNA in blood circulation (B) Phagocytosis: The phagocyte cells (macrophages) removes siRNA from blood circulation via clearance through liver, lungs, and spleen (C) Tissue penetration: Repulsion interactions (due to anionic charge) between siRNA and plasma membrane of endothelial cells prevent internalization of siRNA into cells, only transported by transcellular and paracellular transport mechanisms.
Fig. 4
Fig. 4
Schematic diagram of nanocarrier chemotherapeutics-siRNA co-delivery system synergistically enhance their individual anticancer effects.

Similar articles

Cited by

References

    1. Acharya R. The recent progresses in shRNA-nanoparticle conjugate as a therapeutic approach. Mater. Sci. Eng. C. 2019;104(June):109928. doi: 10.1016/j.msec.2019.109928. - DOI - PubMed
    1. Amreddy N., et al. Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment. Nanomed. Nanotechnol. Biol. Med. 2018;14(2):373–384. doi: 10.1016/j.nano.2017.11.010. - DOI - PMC - PubMed
    1. Andreozzi P., et al. Exploring the pH sensitivity of poly(allylamine) phosphate supramolecular nanocarriers for intracellular siRNA delivery. ACS Appl. Mater. Interfaces. Nov. 2017;9(44):38242–38254. doi: 10.1021/acsami.7b11132. - DOI - PubMed
    1. Attia M.F., Anton N., Wallyn J., Omran Z., Vandamme T.F. An overview of active and passive targeting strategies to improve the nanocarriers efficiency to tumour sites. J. Pharm. Pharmacol. Aug. 2019;71(8):1185–1198. doi: 10.1111/JPHP.13098. - DOI - PubMed
    1. Babu A., Munshi A., Ramesh R. Combinatorial therapeutic approaches with RNAi and anticancer drugs using nanodrug delivery systems. Drug Dev. Ind. Pharm. 2017;43(9):1391–1401. doi: 10.1080/03639045.2017.1313861. - DOI - PMC - PubMed

Further reading

    1. Baghirov H., et al. Feasibility study of the permeability and uptake of mesoporous silica nanoparticles across the blood-brain barrier. PLoS One. 2016;11(8) doi: 10.1371/journal.pone.0160705. - DOI - PMC - PubMed
    1. Gangopadhyay S., Nikam R.R., Gore K.R. Folate receptor-mediated small interfering RNA delivery: recent developments and future directions for RNA interference therapeutics. Feb. 2021. https://home.liebertpub.com/nat - PubMed
    1. Hillaireau H., Couvreur P. Nanocarriers' entry into the cell: relevance to drug delivery. Cell. Mol. Life Sci. 2009;66(17):2873–2896. doi: 10.1007/S00018-009-0053-Z. - DOI - PMC - PubMed
    1. Lee C.H., Ni Y.H., Chen C.C., Chou C.K., Chang F.H. Synergistic effect of polyethylenimine and cationic liposomes in nucleic acid delivery to human cancer cells. Biochim. Biophys. Acta Biomembr. Apr. 2003;1611(1–2):55–62. doi: 10.1016/S0005-2736(03)00027-0. - DOI - PubMed
    1. Li A., et al. The gene transfection and endocytic uptake pathways mediated by PEGylated PEI-entrapped gold nanoparticles. Arab. J. Chem. Jan. 2020;13(1):2558–2567. doi: 10.1016/J.ARABJC.2018.06.009. - DOI

LinkOut - more resources