Advances in Nanomaterials Used in Co-Delivery of siRNA and Small Molecule Drugs for Cancer Treatment

Abstract

Recent advancements in nanotechnology have improved our understanding of cancer treatment and allowed the opportunity to develop novel delivery systems for cancer therapy. The biological complexities of cancer and tumour micro-environments have been shown to be highly challenging when treated with a single therapeutic approach. Current co-delivery systems which involve delivering small molecule drugs and short-interfering RNA (siRNA) have demonstrated the potential of effective suppression of tumour growth. It is worth noting that a considerable number of studies have demonstrated the synergistic effect of co-delivery systems combining siRNA and small molecule drugs, with promising results when compared to single-drug approaches. This review focuses on the recent advances in co-delivery of siRNA and small molecule drugs. The co-delivery systems are categorized based on the material classes of drug carriers. We discuss the critical properties of materials that enable co-delivery of two distinct anti-tumour agents with different properties. Key examples of co-delivery of drug/siRNA from the recent literature are highlighted and discussed. We summarize the current and emerging issues in this rapidly changing field of research in biomaterials for cancer treatments.

Recent Advances in Nanoparticle-Based Co-Delivery Systems for Cancer Therapy

“…Nanocarriers possess unique characteristics, such as a nanometric size, a high surface area to volume ratio, advantageous drug release patterns, and targeting qualities that can help them accumulate preferentially in tumor tissues [ 15 ]. Most importantly, nanomaterials can significantly increase the accumulation of their load at tumor locations by utilizing the enhanced permeability and retention effect (EPR) [ 4 , 30 ]. EPR is a phenomenon that is hypothesized to be caused by leaky tumor vasculature and poor lymphatic outflow.…”

“…Various inorganic nanoparticles have been developed, such as mesoporous silica nanoparticles (MSNs), gold nanoparticles (Au NPs), quantum dots, and iron-based nanoparticles. Using inorganic nanoparticles as co-delivery carriers frequently necessitates nanoparticle modification [ 4 , 13 ]. To accomplish an efficient and successful co-delivery, two or more physical or chemical modifications can be used.…”

“…None of the inorganic nanoparticles for co-delivery have been approved to be available on the market as they have not yet crossed the first clinical stages. Pegylated colloidal gold nanoparticles conjugated to tumor necrosis factor-alpha (TNFa) particles for cancer therapy and silicon nanocarriers for parenteral peptide administration, for example, are in early clinical development [ 4 , 32 ]. At the moment, gold and mesoporous silica nanoparticles are receiving the greatest attention in terms of experimentation and development [ 31 ].…”

“…Advancements in modern anti-cancer therapies, such as gene therapy, have also achieved remarkable results in synergistic anti-tumor effects. Likewise, immunotherapy is also considered a promising therapeutic platform [ 4 ], where researchers manipulate the body’s immune system to hinder the haphazard division and spread of cancer cells through the bloodstream and into adjacent organs and other tissues [ 5 ]. Despite the latter advances, cancer treatment continues to be strenuous and challenging due to the complexity of cancer, and hence conventional chemotherapy remains the fundamental therapeutic approach [ 4 , 5 , 6 ].…”

“…Likewise, immunotherapy is also considered a promising therapeutic platform [ 4 ], where researchers manipulate the body’s immune system to hinder the haphazard division and spread of cancer cells through the bloodstream and into adjacent organs and other tissues [ 5 ]. Despite the latter advances, cancer treatment continues to be strenuous and challenging due to the complexity of cancer, and hence conventional chemotherapy remains the fundamental therapeutic approach [ 4 , 5 , 6 ]. Chemotherapy, defined as the systemic administration of cytotoxic agents that halt the division and proliferation of cancer cells, has several side effects that limit its effectiveness [ 6 ], including (i) low solubility and bioavailability, that often results in irregular biodistribution, causing poor localization of the chemotherapeutic agent at the tumor site, (ii) detrimental systemic toxicity, that affects normal cells and healthy tissues [ 7 ], and (iii) multi-drug resistance (MDR) induced by long-term and continuous administration, which is considered a critical consequence [ 5 , 6 , 8 , 9 ].…”