Exosomes as Drug Delivery Systems: Endogenous Nanovehicles for Treatment of Systemic Lupus Erythematosus

Abstract

Exosomes, nanometer-sized lipid-bilayer-enclosed extracellular vesicles (EVs), have attracted increasing attention due to their inherent ability to shuttle proteins, lipids and genes between cells and their natural affinity to target cells. Their intrinsic features such as stability, biocompatibility, low immunogenicity and ability to overcome biological barriers, have prompted interest in using exosomes as drug delivery vehicles, especially for gene therapy. Evidence indicates that exosomes play roles in both immune stimulation and tolerance, regulating immune signaling and inflammation. To date, exosome-based nanocarriers delivering small molecule drugs have been developed to treat many prevalent autoimmune diseases. This review highlights the key features of exosomes as drug delivery vehicles, such as therapeutic cargo, use of targeting peptide, loading method and administration route with a broad focus. In addition, we outline the current state of evidence in the field of exosome-based drug delivery systems in systemic lupus erythematosus (SLE), evaluating exosomes derived from various cell types and engineered exosomes.

Exosomes Engineering and Their Roles as Therapy Delivery Tools, Therapeutic Targets, and Biomarkers

“…The route of administration of therapeutic biomaterials affects their distribution in tissues. Among all the mentioned routes, the intravenous route of therapeutics administration is the most commonly used and researched [2,11,102,147,173]. A brief description of the abovementioned administration routes of therapeutic biomaterials into the body through drug delivery (Figure 13), based on various studies performed in animal models, is presented below.…”

“…Intravenous injection, administration of drugs into the vein, is the most common route of administration, although it can lead to the accumulation of exosomes in the liver, spleen, and lung, and they can also be cleared from the circulation extremely quickly [173].…”

“…Representative structure of different administration routes of therapeutic biomaterials into the body through drug delivery: intravenous injection, intranasal administration, oral administration, intraperitoneal injection, subcutaneous injection, intratumoral injection, and intradermal injection (summarized from [2,11,102,147,173]).…”

“…Qu et al [174] determined that exosomes produced from mouse blood reticulocytes and loaded with dopamine have better therapeutic abilities in the treatment of Parkinson's Figure 13. Representative structure of different administration routes of therapeutic biomaterials into the body through drug delivery: intravenous injection, intranasal administration, oral administration, intraperitoneal injection, subcutaneous injection, intratumoral injection, and intradermal injection (summarized from [2,11,102,147,173]).…”

Mesenchymal stem cells and their derived exosomes to combat Covid–19

“…Exosomes have attracted increasing attention from drug delivery systems in the past decade owing to their intrinsic properties such as high stability, biodegradability, biocompatibility, prolonged circulation time, low immunogenicity, and the ability to pass blood barriers, all of which represent exosomes an ideal carrier for therapeutic agents such as anti‐viral drugs and miRNAs. 88 , 89 , 90 Exosomes injected intravenously accumulate in the damaged tissues and inflammation sites by preference, 91 resulting in a passive targeting delivery of exosome cargo. Similar to other lipid‐bilayer nanocarriers, exosomes can be tissue‐specifically targeted by surface modifications to enhance and improve their targeting activity.…”