Organotropic drug delivery: Synthetic nanoparticles and extracellular vesicles

Abstract

Most clinically approved drugs (primarily small molecules or antibodies) are rapidly cleared from circulation and distribute throughout the body. As a consequence, only a small portion of the dose accumulates at the target site, leading to low efficacy and adverse side effects. Therefore, new delivery strategies are necessary to increase organ and tissue-specific delivery of therapeutic agents. Nanoparticles provide a promising approach for prolonging the circulation time and improving the biodistribution of drugs. However, nanoparticles display several limitations, such as clearance by the immune systems and impaired diffusion in the tissue microenvironment. To overcome common nanoparticle limitations various functionalization and targeting strategies have been proposed. This review will discuss synthetic nanoparticle and extracellular vesicle delivery strategies that exploit organ-specific features to enhance drug accumulation at the target site.

Adipose‐Derived Biogenic Nanoparticles for Suppression of Inflammation

“…Therefore, we hypothesized that loading Lipo‐NPs with GBZ could further suppress TLR4‐induced inflammatory cytokines. Additionally, there are several advantages of NP‐encapsulation as opposed to co‐administration of a free drug, including prolonged circulation times, enhanced site‐specific delivery, reduced side effects, and simultaneous delivery with other NP cargo 17–19…”

“…Although the loading of therapeutic agents, such as RNAs and proteins, in BiNPs is usually highly inefficient,63 this study demonstrates that high levels of hydrophobic small molecules can be loaded in BiNPs. However, it is unclear whether this dose of GBZ would be sufficient for in vivo use, although previous studies have demonstrated that nanoparticle loading of therapeutic drugs improves circulation times and site‐specific delivery, reducing the required dose 17–21…”

“…However, in vivo, small molecules undergo rapid renal clearance, which is prevented with nanoparticle encapsulation. Therefore, nanoparticle‐encapsulated drugs usually outperform their free counterparts in vivo due to size‐mediated prolonged circulation times and also improved targeted delivery 17–21…”

Brain metastases-derived extracellular vesicles induce binding and aggregation of low-density lipoprotein

“…Animal studies have demonstrated that pretreatment with pro-metastatic EVs prior to cancer cell injection can substantially increase the formation of subsequent metastatic lesions [ 4 , 9 , 10 ]. Evidence suggests that EV-mediated metastatic organotropism involves integrin interactions with tissue-specific epithelial, endothelial, or resident immune cells [ 4 , 11 ]. Cancer cell-derived EVs have also been shown to carry microRNAs (miRNAs) that disrupt the integrity of endothelial barriers in distant organs [ 12 , 13 ].…”

Design and Synthesis of ZnII‐Coordination Polymers Anchored with NSAIDs: Metallovesicle Formation and Multi‐drug Delivery

“…Ever since the first report of synthetic vesicles derived from a simple organic molecule by Kunitake et al. in late 70′s of the last century, there have been abundance of examples of synthetic vesicles derived from organic molecules, that are actively being pursued as potential drug delivery vehicles . However, there are obvious impediments (e.g.…”