Nanocarrier mediated delivery of siRNA/miRNA in combination with chemotherapeutic agents for cancer therapy: current progress and advances.

Chemotherapeutic agents have certain limitations when it comes to treating cancer, the most important being severe side effects along with multidrug resistance developed against them. Tumor cells exhibit drug resistance due to activation of various cellular level processes viz. activation of drug efflux pumps, anti-apoptotic defense mechanisms, etc. Currently, RNA interference (RNAi) based therapeutic approaches are under vibrant scrutinization to seek cancer cure. Especially small interfering RNA (siRNA) and micro RNA (miRNA), are able to knock down the carcinogenic genes by targeting the mRNA expression, which underlies the uniqueness of this therapeutic approach. Recent research focus in the regime of cancer therapy involves the engagement of targeted delivery of siRNA/miRNA in combinations with other therapeutic agents (such as gene, DNA or chemotherapeutic drug) for targeting permeability glycoprotein (P-gp), multidrug resistant protein 1 (MRP-1), B-cell lymphoma (BCL-2) and other targets that are mainly responsible for resistance in cancer therapy. RNAi-chemotherapeutic drug combinations have also been found to be effective against different molecular targets as well and can increase the sensitization of cancer cells to therapy several folds. However, due to stability issues associated with siRNA/miRNA suitable protective carrier is needed and nanotechnology based approaches have been widely explored to overcome these drawbacks. Furthermore, it has been univocally advocated that the co-delivery of siRNA/miRNA with other chemodrugs significantly enhances their capability to overcome cancer resistance compared to naked counterparts. The objective of this article is to review recent nanocarrier based approaches adopted for the delivery of siRNA/miRNA combinations with other anticancer agents (siRNA/miRNA/pDNA/chemodrugs) to treat cancer.

Gandhi NS ，Tekade RK ，Chougule MB 《-》

Combinatorial therapeutic approaches with RNAi and anticancer drugs using nanodrug delivery systems.

Babu A ，Munshi A ，Ramesh R 《-》

Simultaneous nanocarrier-mediated delivery of siRNAs and chemotherapeutic agents in cancer therapy and diagnosis: Recent advances.

Recently, investigations have revealed that RNA interference (RNAi) has a remarkable potential to decrease cancer burden by downregulating genes. Among various RNAi molecules, small interfering RNA (siRNA) has been more attractive for this goal and is able to silence a target pathological path and promote the degradation of a certain mRNA, resulting in either gain or loss of function of proteins. Moreover, therapeutic siRNAs have exhibited low side effects compared to other therapeutic molecular candidates. Nevertheless, siRNA delivery has its own limitations including quick degradation in circulation, ineffective internalization and low passive uptake by cells, possible toxicity against off-target sites, and inducing unfavorable immune responses. Therefore, delivery tools must be able to specifically direct siRNAs to their target locations without inflicting detrimental effects on other sites. To conquer the mentioned problems, nanocarrier-mediated delivery of siRNAs, using inorganic nanoparticles (NPs), polymers, and lipids, has been developed as a biocompatible delivery approach. In this review, we have discussed recent advances in the siRNA delivery methods that employ nanoparticles, lipids, and polymers, as well as the inorganic-based co-delivery systems used to deliver siRNAs and anticancer agents to target cells.

Bidar N ，Darroudi M ，Ebrahimzadeh A ，Safdari M ，de la Guardia M ，Baradaran B ，Goodarzi V ，Oroojalian F ，Mokhtarzadeh A ... -  《-》

RNAi-combined nano-chemotherapeutics to tackle resistant tumors.

The merger of nanotechnology and combination chemotherapy has shown notable promise in the therapy of resistant tumors. The latest scientific attention encompasses the engagement of anticancer drugs in combination with small interfering (si)RNAs, such as VEGF, XLAP, PGP, MRP-1, BCL-2 and cMyc, to name but a few. siRNAs have shown immense promise to knockout drug resistance genes as well as to recover the sensitivity of resistant tumors to anticancer therapy. The nanotechnology approach could also protect siRNA against RNAse degradation as well as prevent off-target effects. In this article, we discuss the approaches that have been used to deliver of siRNA in combination with chemotherapeutic drugs to treat resistant tumors. We also discuss the stipulations that must be considered in formulating a nanotechnology-assisted siRNA-drug cancer therapy.

Tekade RK ，Tekade M ，Kesharwani P ，D'Emanuele A ... -  《-》

Chemotherapy with si-RNA and Anti-Cancer Drugs.

To treat cancer, chemotherapy is a key therapeutic approach which is associated with several limitations. This chemotherapeutical agent exhibits multi drug resistance coupled with undesirable side effects. This multidrug resistance is exhibited by tumor cell due to actuation of drug out flow mechanism, programmed cell death and protection mechanisms etc. One of the therapeutic approaches to cure cancer is RNA interference (RNAi). Small interfering RNA (si-RNA) is considered as a major therapeutic tool used to control expression of a particular gene. It is a well known fact that intake of more drugs can lead to cancer chemo resistance, thus siRNA based therapeutic approach is under scrutiny to cure cancer. This review article gives an overview of various combination approaches for si-RNA with chemotherapeutics. Further, article highlights the potential of nanotechnology to improve bioavailability of drug and bio-therapeutics at the site of action. Combination chemotherapy is employed in clinics as a main cancer treatment tool to suppress multidrug resistance in cancer. On the other hand, suitable protective carrier is needed due to the stability issues and small size of si-RNA. To overcome these drawbacks associated with siRNA currently, nanotechnology based approaches have been widely used. Delivery of anti-cancer drugs with si-RNA will be one of important intermingled approach to reduce duration of chemotherapy and improve therapeutic outcomes in cancer patient.

Kaur K ，Rath G ，Chandra S ，Singh R ，Goyal AK ... -  《-》