Extracellular vesicle‐based nucleic acid delivery

Abstract Extracellular vesicles (EVs) are a heterogeneous class of natural vesicles that facilitate intercellular communication by functional transfer of lipids and biomolecular cargoes, such as miRNAs, mRNAs and proteins. As a naturally occurring delivery vehicle for nucleic acids, EVs are characterized by multiple advantageous characteristics, such as unique size and structure, excellent biocompatibility, immunologically inert, increased stability in circulation, intrinsic targeting capacity and the capability of membrane fusion and crossing biological barriers. Of note, the delivery properties of EVs can be further improved by genetic engineering of donor cells or direct modification of EVs. Over the last decade, EVs have sparkled intensive interest for delivery of small RNAs, including small interfering RNAs (siRNAs) and microRNAs (miRNAs). In recent years, increasing attention has been focused on exploring a variety of strategies to harness EVs for delivery of more nucleic acid types. In the present perspective, we provide a capsule overview of the latest accomplishments and trends in the field of EV‐based delivery systems for siRNAs, miRNAs, messenger RNAs (mRNAs), clustered regularly interspaced short palindromic repeats‐associated endonuclease (CRISPR/Cas) systems, antisense oligonucleotides (ASOs), circular RNA (circRNAs), long noncoding RNAs (lncRNAs) and DNAs. This perspective may offer insights into the rational design of more cutting‐edge extracellular vesicle‐based nucleic acid delivery nanoplatforms

Surface Charge of Supramolecular Nanosystems for In Vivo Biodistribution: A MicroSPECT/CT Imaging Study

Bioimaging has revolutionized medicine by providing accurate information for disease diagnosis and treatment. Nanotechnology-based bioimaging is expected to further improve imaging sensitivity and specificity. In this context, supramolecular nanosystems based on self-assembly of amphiphilic dendrimers for single photon emission computed tomography (SPECT) bioimaging are developed. These dendrimers bear multiple In3+ radionuclides at their terminals as SPECT reporters. By replacing the macrocyclic 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid cage with the smaller 1,4,7-triazacyclononane-1,4,7-triacetic acid scaffold as the In3+ chelator, the corresponding dendrimer exhibits neutral In3+ -complex terminals in place of negatively charged In3+ -complex terminals. This negative-to-neutral surface charge alteration completely reverses the zeta-potential of the nanosystems from negative to positive. As a consequence, the resulting SPECT nanoprobe generates a highly sought-after biodistribution profile accompanied by a drastically reduced uptake in liver, leading to significantly improved tumor imaging. This finding contrasts with current literature reporting that positively charged nanoparticles have preferential accumulation in the liver. As such, this study provides new perspectives for improving the biodistribution of positively charged nanosystems for biomedical applications