RNAi nanomaterials targeting immune cells as an anti-tumor therapy: the missing link in cancer treatment?

Gold Nanoparticle Approach to the Selective Delivery of Gene Silencing in Cancer—The Case for Combined Delivery?

“…Moreover, tumor-associated immune cells are major contributors to the tumor microenvironment (TME) as well as tumor growth and development [80]. Nowadays, the focus has been mostly on tackling more advanced stages (metastasized tumors), profiting from the seek-and-destroy capability of the immune-drugs.…”

“…Cancerous cells are recognized and their elimination is induced through immune cells, in a first line of defense via macrophages, neutrophils, and natural killer (NK) cells (innate cells), mediated through their cytotoxic mechanisms; and in a second line by macrophages and dendritic cells (DCs), which present tumor-associated antigens (TAAs) to T cells and induce a potent adaptive immune response. However, tumors develop mechanisms to evade the immune system, including changing the expression of surface molecules to become undetectable to immune cells and inducing immunotolerance by actively suppressing tumor-directed immunogenic responses (immunoediting) [80]. …”

“…This immunostimulation is related to siRNA structure and sequence, siRNA delivery system, and cell type, and it occurs when there is a link between cellular antiviral systems and the siRNA pathway [79]. In addition, intrinsic inhibitory pathways can be abolished and further immunity function can be empowered by RNAi, allowing an inhibition of immune suppression [80,81]. The combination of gene silencing with other immunotherapies can target cells from different aspects, thus possibly decreasing the tumor immune invasion.…”

MicroRNAs in Cancer: Challenges and Opportunities in Early Detection, Disease Monitoring, and Therapeutic Agents

“…In fact, recent studies have shown that in specific types of cancer such as CRC, the TME gene expression profiles are better predictors of overall survival rather than tumor cell gene expression profiles [65, 66]. Development of tools taking advantage of the physical and chemical nature of the TME for targeting RNA therapies has become an attractive research focus [67, 68]. For example, Cheng and colleagues utilized a novel hybrid molecule consisting of a peptide nucleic acid miRNA antagonist linked to a low pH-transmembrane structure (pHLIP) that preferentially targets the inherent acidity of the TME.…”

Cancer Nanotheranostics: What Have We Learned so Far?

“…As such, the effect and response of diverse properties of nanodiagnostics platforms in the organisms have been discussed by Clift et al [12], where nanoconjugates are discussed in terms of the immune response triggered after systemic delivery; whereas Conniot et al [13] and Pearson et al [14] have demonstrated how nanotheranostics may use and profit from the specific and unspecific immune response to enhance efficacy. Actually, cancer immunotherapy is nowadays consider a hot topic and a huge breakthrough in modern Science [15].…”