Future trends and emerging issues for nanodelivery systems in oral and oropharyngeal cancer

Abstract

Oral cancer is a prevalent cancer type on a global scale, whose traditional treatment strategies have several drawbacks that could in the near future be overcome through the development of novel therapeutic and prognostic strategies. Nanotechnology provides an alternative to traditional therapy that leads to enhanced efficiency and less toxicity. Various nanosystems have been developed for the treatment of oral cancer, including polymeric, metallic, and lipid-based formulations that incorporate chemotherapeutics, natural compounds, siRNA, or other molecules. This review summarizes the main benefits of using these nanosystems, in parallel with a particular focus on the issues encountered in medical practice. These novel strategies have provided encouraging results in both in vitro and in vivo studies, but few have entered clinical trials. The use of nanosystems in oral cancer has the potential of becoming a valid therapeutic option for patients suffering from this malignancy, considering that clinical trials have already been completed and others are currently being developed.

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

“…While siRNAs and other small molecules (with sizes <8 nm) are removed via renal clearance, larger nano‐scale objects are readily identified by the body's immune system to be phagocytosed by macrophages in the major RES organs, such as the liver, spleen, and lungs . The primary mechanism by which the immune cells recognize and clear these objects is by opsonization, where molecules that recognize foreign body (opsonins; e.g., antibodies) bind to the surface of the target to label them for phagocytic clearance by the complement immune response . The effect may be diminished by adjusting the particle properties, such as size and shape, surface chemistry (e.g., PEGylation), and surface charge (decreased clearance is observed in positive compared to neutral and negative surface charges) .…”

“…Based on published data accumulated over the past decade, average gene silencing efficiencies of 64.6 ± 24.7% in vitro and 61.5 ± 19.6% in vivo have been achieved (Figure and Table ). The three most frequently employed types of polymer nanoparticles for siRNA delivery have been solid polymeric nanoparticles, dendrimers, and hydrogels, but across the wide range of structural designs in polymeric delivery systems, there are a number of proven components that are regularly used: poly(lactic‐co‐glycolic acid) (PLGA), poly‐L‐lysine (PLL), chitosan, and polyethyleneimine (PEI) …”

RNA interference: new mechanistic and biochemical insights with application in oral cancer therapy

“…Neutral liposomes have a size of 30-40 nm and are the most commonly used lipid-based nanosystems. 36 siRNA therapy is well-tolerated, but in some cases, particularly for the case of transcripts with .23 nucleotides, interferon responses can be activated together with the induction of cell death within in vitro systems. The immune reaction is different, dependent of the type of cells used, and it is hard to predict the in vivo responses.…”

“…49 siRNA delivery strategies that use viral particles have a constitutive effect while different nanostructures have only a transitory effect, implying multiple administration doses. 36 The viral delivery of siRNA is composed of two main strategies: siRNA is either chemically synthesized and loaded into a viral capsule or it can be expressed from the DNA of a recombinant virus. The major disadvantages of viral siRNA delivery are lower targeted delivery of a specific cell in vivo, the host immune reaction, and the danger of oncogenic transformation of the virus.…”

Microfluidic On-demand Engineering of Exosomes towards Cancer Immunotherapy

“…Compared to other nano-sized delivery systems, such as lipid, polymers, gold, and silica material [27][28][29][30][31][32] , exosomes are living-cell derived, highly biocompatible nano-carriers with intrinsic payload, and exhibit much stronger flexibility in loading desired antigens for effective delivery 33 . Exosomes also eliminate allergenic responses without concerns of carrying virulent factors and avoid degradation or loss during delivery [34][35] .…”