Abstract
The proposal of gene therapy to tackle cancer development has been instrumental for the development of novel approaches and strategies to fight this disease, but the efficacy of the proposed strategies has still fallen short of delivering the full potential of gene therapy in the clinic. Despite the plethora of gene modulation approaches, e.g., gene silencing, antisense therapy, RNA interference, gene and genome editing, finding a way to efficiently deliver these effectors to the desired cell and tissue has been a challenge. Nanomedicine has put forward several innovative platforms to overcome this obstacle. Most of these platforms rely on the application of nanoscale structures, with particular focus on nanoparticles. Herein, we review the current trends on the use of nanoparticles designed for cancer gene therapy, including inorganic, organic, or biological (e.g., exosomes) variants, in clinical development and their progress towards clinical applications.
Highlights
According to the World Health Organization, cancer is the second leading cause of death worldwide, accounting for 9.6 million deaths in 2018 [1]
Regardless of the described challenges for gene induced expression mediated by nanoparticles, that end up in modest antitumor effects, the observed severe toxicity related with increased IL-12 concentration in serum triggered the re-focusing towards anticancer therapies that combine the effect of IL-12 with other antitumor strategies, e.g., synergistic effect of IL-12 with other cytokines, such as tumor necrosis factors (TNF)-α, or GM-CSF, using anti-angiogenic factors, such as VEGF inhibitors, suicide gene therapy or chemotherapy [133,134,135]
Nanomedicine has been providing conceptual solutions to the limitations faced by viral-based gene delivery
Summary
According to the World Health Organization, cancer is the second leading cause of death worldwide, accounting for 9.6 million deaths in 2018 [1]. Major common features of tumor cells include continuous proliferative signaling, evasion of growth suppressors, resisting cell death, replicative immortality, deregulating cellular energetics, promoting angiogenesis, activating invasion and metastasis, and avoiding immune destruction [3] These features sustain the foundation of a TME composed by a characteristic extracellular matrix (ECM), cancer-associated fibroblasts (CAFs), mesenchymal stromal cells, endothelial cells and pericytes, and immune system cells, such as macrophages, T and B lymphocytes and natural killer cells (reviewed in [4]). For gene therapy it is necessary that the vector and payload pass across the complex hydrophobic layer of the tumor cell membrane [41] This mainly occurs via endocytosis mediated by ligand-receptor specific, using active targeting, or non-specific, such as electrostatic or hydrophobic, interactions with the cell membrane (reviewed in [40,65,66]). TThheerraappiieess ttaarrggeettiinngg tthhee ttuummoorrmmicircoroenenvviriornonmmenetn(tin(ingregernee),ni)n,cilnucdliundginagngaionggeiongeesinsetsairsgteatringgettihnegrathpey,raimpym, uimnimzautinoinzagteionne tgheenreapthye, rtaaprgye,ttianrggectainncgecraanscseorcaiastseodcifiatberdobfilbarsotsblaansdtstaanrgdettainrggettuinmgotrumceollrscdeellrsivdeedrievxeodseoxmoseos,maelsso, aulssoe tuhseedtehsecridbeesdcrmiboeldecumlaorlesctrualtaergisetsra(itnegpiuesrp(lien), spuucrhplaes),gesnuecshreapslagceenmeesntr,egpelanceesmileennct,ingge, ntreanssilcernipctiinogn, ftaracntosrcrdiepctoioyns,fmacitRorNdAectoarygse, tmediRtNheAratpayrgaenteddgtehneormapeyeadnitdingge.nome editing
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