Nanotechnological Approaches in Prostate Cancer Therapy: Integration of engineering and biology

Pancreatic cancer is one of the most lethal forms of cancer, predicted to be the second leading cause of cancer-associated death by 2025. Despite intensive research for effective treatment strategies and novel anticancer drugs over the past decade, the overall patient survival rate remains low. RNA interference (RNAi) is capable of interfering with expression of specific genes and has emerged as a promising approach for pancreatic cancer because genetic aberrations and dysregulated signaling are the drivers for tumor formation and the stromal barrier to conventional therapy. Despite its therapeutic potential, RNA-based drugs have remaining hurdles such as poor tumor delivery and susceptibility to serum degradation, which could be overcome with the incorporation of nanocarriers for clinical applications. Here we summarize the use of small interfering RNA (siRNA) and microRNA (miRNA) in pancreatic cancer therapy in preclinical reports with approaches for targeting either the tumor or tumor microenvironment (TME) using various types of nanocarriers. In these studies, inhibition of oncogene expression and induction of a tumor suppressive response in cancer cells and surrounding immune cells in TME exhibited a strong anticancer effect in pancreatic cancer models. The review discusses the remaining challenges and prospective strategies suggesting the potential of RNAi-based therapeutics for pancreatic cancer.

RNAi-Based Approaches for Pancreatic Cancer Therapy.

Small interfering RNAs based therapies for intracerebral hemorrhage: challenges and progress in drug delivery systems

Recent advances in the manufacturing, modification, purification, and cellular delivery of ribonucleic acid (RNA) have enabled the development of RNA-based therapeutics for a broad array of applications. The approval of two SARS-CoV-2-targeting mRNA-based vaccines has highlighted the advances of this technology. Offering rapid and straightforward manufacturing, clinical safety, and versatility, this paves the way for RNA therapeutics to expand into cancer immunotherapy. Together with ongoing trials on RNA cancer vaccination and cellular therapy, RNA therapeutics could be introduced into clinical practice, possibly stewarding future personalized approaches. In the present review, we discuss recent advances in RNA-based immuno-oncology together with an update on ongoing clinical applications and their current challenges. 

RNA in Cancer Immunotherapy: Unlocking the Potential of the Immune System

Simple Summary Natural killer cells are a part of the native immune response to cancer. NK cell-based immunotherapies are an emerging strategy to kill tumor cells. This paper reviews the role of NK cells, their mechanism of action for killing tumor cells, and the receptors which could serve as potential targets for signaling. In this review, the role of nanoparticles in NK cell activation and increased cytotoxicity of NK cells against cancer are highlighted. Abstract Natural killer (NK) cells are one of the first lines of defense against infections and malignancies. NK cell-based immunotherapies are emerging as an alternative to T cell-based immunotherapies. Preclinical and clinical studies of NK cell-based immunotherapies have given promising results in the past few decades for hematologic malignancies. Despite these achievements, NK cell-based immunotherapies have limitations, such as limited performance/low therapeutic efficiency in solid tumors, the short lifespan of NK cells, limited specificity of adoptive transfer and genetic modification, NK cell rejection by the patient’s immune system, insignificant infiltration of NK cells into the tumor microenvironment (TME), and the expensive nature of the treatment. Nanotechnology could potentially assist with the activation, proliferation, near-real time imaging, and enhancement of NK cell cytotoxic activity by guiding their function, analyzing their performance in near-real time, and improving immunotherapeutic efficiency. This paper reviews the role of NK cells, their mechanism of action in killing tumor cells, and the receptors which could serve as potential targets for signaling. Specifically, we have reviewed five different areas of nanotechnology that could enhance immunotherapy efficiency: nanoparticle-assisted immunomodulation to enhance NK cell activity, nanoparticles enhancing homing of NK cells, nanoparticle delivery of RNAi to enhance NK cell activity, genetic modulation of NK cells based on nanoparticles, and nanoparticle activation of NKG2D, which is the master regulator of all NK cell responses.

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Nanoparticle Enhancement of Natural Killer (NK) Cell-Based Immunotherapy

RNAi effectors (e.g., siRNA, shRNA, and miRNA) can efficiently trigger the silencing of specific genes, and its genomic alteration functions allowed to pursue clinical trials in distinct areas, including infectious diseases, neurodegenerative disorders, and cancer. Moreover, regarding cancer immunotherapy, RNAi therapeutics showed potential immunomodulatory ability by downregulating suppressive receptors such as PD-1 and CTLA-4, which restrict immune cell function and present challenges in cancer immunotherapy. Therefore, compared with extracellular targeting by antibodies, RNAi-mediated, cell-intrinsic disruption of inhibitory pathways in immune cells can promote an increased antitumor immune response. Along with nonviral vectors, DNA-based RNAi strategies might be a more promising method for immunomodulation to silence multiple inhibitory pathways in T cells than immune checkpoint blockade antibodies. Thus, in this review, we discuss diverse RNAi implementation strategies, with recent viral and non-viral mediated RNAi synergism to immunotherapy that augments the antitumor immunity. Finally, we provide the current progress of RNAi in clinical pipeline.

Xu Nan

Papers

Emerging role of RNA interference in immune cells engineering and its therapeutic synergism in immunotherapy.