Advanced strategies for nucleic acids and small-molecular drugs in combined anticancer therapy

Abstract

Cancer has been considered as complex malignant consequence of genetic mutations that control the cellular proliferation, differentiation and homeostasis, thus making tumor treatment extremely challenging. To date, a variety of cargo molecules, including nucleic acids drugs (pDNA, miRNA and siRNA), therapeutic drugs (doxorubicin, paclitaxel, daunomycin and gefitinib) and imaging agents (radioisotopes, fluorescence dyes, and MRI contrast agents) have been regarded as the potential medicines in clinical application. However, non-single therapeutic drug could induce the satisfied clinical results because of tumor heterogeneity and multiple drug resistance and the nanotechnology-based combined therapy is becoming an advanced important mode for enhanced anticancer effects. The review gathers the current advanced development to co-deliver small-molecular drugs and nucleic acids for the anticancer therapy with nanomedicine-based combination. Furthermore, the superiority is definitely presented and the barriers are detail discussed to surmount the clinical challenges. In final, future perspectives in rational direction for combined tumor therapy of drugs and nucleic acids are exhibited.

Bioengineered chimeric tRNA/pre‐miRNAs as prodrugs in cancer therapy

“…GOA/miRNA nanoparticles can effectively penetrate into cancer cells after intravenous injection and significantly inhibit tumor growth. 33 GOA/miR-122 and GOA/miR-34a nanoparticles inhibited the migration and proliferation of HepG2 hepatocellular carcinoma cells by affecting CCNG1, SIRT1, and Notch1. 34 Other delivery systems for better bioavailability are polyethylene glycol (PEG)-contained liposomes, biodegradable polymers, and lipidoids.…”

“…Gemcitabine‐oleic acid conjugate (GOA) is a synthetic amphiphilic gemcitabine prodrug that could carry miRNAs. GOA/miRNA nanoparticles can effectively penetrate into cancer cells after intravenous injection and significantly inhibit tumor growth 33 . GOA/miR‐122 and GOA/miR‐34a nanoparticles inhibited the migration and proliferation of HepG2 hepatocellular carcinoma cells by affecting CCNG1, SIRT1, and Notch1 34 .…”

Folate-Targeted Nanocarriers Co-Deliver Ganciclovir and miR-34a-5p for Combined Anti-KSHV Therapy

“…Due to the complexity of the KSHV infection site, monotherapeutic agents cannot achieve satisfactory therapeutic effects. At present, combination therapy based on nanotechnology is becoming an important model of the advanced enhancement of anti-cancer effects [ 19 , 20 , 21 , 22 ]. One promising anti-KSHV strategy is the design of nanocarriers that can simultaneously load GCV and miR-34a-5p and deliver these two drugs to the KSHV infection site as an anti-KSHV drug combination.…”

What lower the development of nanodrug?

“…Discuss the importance of evaluating the toxicity and biocompatibility of various nanomaterials and delivery systems.Scalability and manufacturing: The translation of these strategies to clinical settings will require scalable and cost-effective manufacturing processes. It is important to discuss the challenges related to scaling up the production of nanodrug delivery systems, as well as the need for standardized protocols to ensure reproducibility and quality control [9] .Regulatory considerations: Address the importance of considering regulatory requirements in the development of nanodrug delivery systems and strategies, particularly as they pertain to safety, efficacy, and quality.Interdisciplinary collaboration: An in-depth understanding of nanocarrier trafficking and metabolization may facilitate the rational design of smarter nanodrug delivery systems [10] . This includes collaborations between researchers from the fields of chemistry, materials science, biology, and medicine, as well as partnerships with industry and regulatory agencies.Of course, other factors will also affect the process of nanodrug development.…”

“…Interdisciplinary collaboration: An in-depth understanding of nanocarrier trafficking and metabolization may facilitate the rational design of smarter nanodrug delivery systems [10] . This includes collaborations between researchers from the fields of chemistry, materials science, biology, and medicine, as well as partnerships with industry and regulatory agencies.…”