Non-viral nucleic acid containing nanoparticles as cancer therapeutics

ABSTRACT

Introduction: The delivery of nucleic acids such as DNA and short interfering RNA (siRNA) is promising for the treatment of many diseases, including cancer, by enabling novel biological mechanisms of action. Non-viral nanoparticles are a promising class of nucleic acid carriers that can be designed to be safer and more versatile than traditional viral vectors.

Areas covered: In this review, recent advances in the intracellular delivery of DNA and siRNA are described with a focus on non-viral nanoparticle-based delivery methods. Material properties that have enabled successful delivery are discussed as well as applications that have directly been applied to cancer therapy. Strategies to co-deliver different nucleic acids are highlighted, as are novel targets for nucleic acid co-delivery.

Expert opinion: The treatment of complex genetically-based diseases such as cancer can be enabled by safe and effective intracellular delivery of multiple nucleic acids. Non-viral nanoparticles can be fabricated to deliver multiple nucleic acids to the same cell simultaneously to prevent tumor cells from easily compensating for the knockdown or overexpression of one genetic target. The continued innovation of new therapeutic modalities and non-viral nanotechnologies to provide target-specific and personalized forms of gene therapy hold promise for genetic medicine to treat diseases like cancer in the clinic.

KEYWORDS:

• Cancer
• DNA
• gene delivery
• gene therapy
• nanoparticle
• polymer
• siRNA

Article highlights

• Obstacles to intracellular nucleic acid delivery include rapid clearance from circulation, tissue and tumor targeting, cellular internalization, endosomal escape, and intracellular release.

• Lipid-based and inorganic materials protect nucleic acids from degradation and condense them into nanoparticles for improved cellular uptake.

• Cationic polymers self-assemble into polyplexes with nucleic acids via electrostatic interactions and possess functional groups to aid in improved cellular uptake, endosomal escape through endosomal buffering, and intracellular cargo release via biodegradable linkages.

• Nanoparticle formulations optimized for the co-delivery of multiple DNA or siRNA cargos can be used to reach novel synergistic cancer therapy targets.

• Therapeutic modalities such as DNA, siRNA, and CRISPR/Cas technology may benefit from non-viral nanoparticle delivery platforms for the treatment of complex genetically-based diseases.

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Declaration of interest

This work was supported in part by the NIH (1R01EB016721). K Kozielski thanks the NIH (1F31CA196163) for fellowship support. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.