Nanoparticles for nucleic acid delivery: Applications in cancer immunotherapy.

Immunotherapy has recently emerged as a powerful tool for cancer treatment. Early clinical successes from cancer immunotherapy have led to a growing list of FDA approvals, and many new therapies are in clinical and preclinical development. Nucleic acid therapeutics, including DNA, mRNA, and genome editing systems, hold significant potential as a form of immunotherapy due to its robust use in cancer vaccination, adoptive T-cell therapy, and gene regulation. However, these therapeutics must overcome numerous delivery obstacles to be successful, including rapid in vivo degradation, poor uptake into target cells, required nuclear entry, and potential in vivo toxicity in healthy cells and tissues. Nanoparticle delivery systems have been engineered to overcome several of these barriers as a means to safely and effectively deliver nucleic acid therapeutics to immune cells. In this Review, we discuss the applications of nucleic acid therapeutics in cancer immunotherapy, and we detail how nanoparticle platforms have been designed to deliver mRNA, DNA, and genome editing systems to enhance the potency and safety of these therapeutics.

Mukalel AJ ，Riley RS ，Zhang R ，Mitchell MJ ... -  《-》

Advances in targeted delivery of mRNA into immune cells for enhanced cancer therapy.

Huang L ，Huang Z ，Zhang Y ，Lin C ，Zhao Z ，Li R ，Saw PE ，Xu X ... -  《Theranostics》

Delivery technologies for cancer immunotherapy.

Riley RS ，June CH ，Langer R ，Mitchell MJ ... -  《-》

Developing Biodegradable Lipid Nanoparticles for Intracellular mRNA Delivery and Genome Editing.

Qiu M ，Li Y ，Bloomer H ，Xu Q ... -  《-》

Nanoscale platforms for messenger RNA delivery.

Messenger RNA (mRNA) has become a promising class of drugs for diverse therapeutic applications in the past few years. A series of clinical trials are ongoing or will be initiated in the near future for the treatment of a variety of diseases. Currently, mRNA-based therapeutics mainly focuses on ex vivo transfection and local administration in clinical studies. Efficient and safe delivery of therapeutically relevant mRNAs remains one of the major challenges for their broad applications in humans. Thus, effective delivery systems are urgently needed to overcome this limitation. In recent years, numerous nanoscale biomaterials have been constructed for mRNA delivery in order to protect mRNA from extracellular degradation and facilitate endosomal escape after cellular uptake. Nanoscale platforms have expanded the feasibility of mRNA-based therapeutics, and enabled its potential applications to protein replacement therapy, cancer immunotherapy, therapeutic vaccines, regenerative medicine, and genome editing. This review focuses on recent advances, challenges, and future directions in nanoscale platforms designed for mRNA delivery, including lipid and lipid-derived nanoparticles, polymer-based nanoparticles, protein derivatives mRNA complexes, and other types of nanomaterials. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures.

Li B ，Zhang X ，Dong Y 《-》