Engineering the future of nanomedicine: Strategic approaches to extracellular vesicle-based drug administration regimens

Table 1 Summary table of key findings

EVs	Key components	Target disease	Research focus	Ref.
Bone marrow MSC-derived extracellular vesicles	Phase 2 multicenter double-anonymized randomized placebo-controlled dosing trial	Respiratory failure rom COVID-19	Clinical trial	Lightner et al[18]
Human placental mesenchymal stromal cell-derived small extracellular vesicles	Double-blind, randomized, controlled clinical trial	Acute respiratory distress syndrome	Clinical trial	Zamanian et al[19]
ExosCD47-HuR	Fusion gene CD47-HuR integrate into LO2 cells via antiviral infection	Hepatic ischemia/reperfusion injury	Engineered vesicles	Liu et al[20]
CD9 engineered ExoSmart	Integrate CD47 p110-130 into the exosomal membrane by engineering CD9 E174	Pancreatic ductal adenocarcinoma	Engineered vesicles	Creeden et al[21]
BV2 mouse microglial cell line exosome	Functional oligopeptide-modified exosome loaded with doxorubicin	Glioblastoma	Engineered vesicles	Wang et al[25]
Bone marrow MSCs derived exosomes	Genetically engineered exosomes expressing chondrocyte-affinity peptide on the surface	Cartilaginous endplate degeneration	Engineered vesicles	Lin et al[27]
MSCs derived exosomes	Anchored cartilage targeting optimally charged arginine-rich cationic motifs into the anionic exosome bilayer	Osteoarthritis	Engineered vesicles	Zhang et al[28]
Adipose-derived stem cell-exosome	Conjugate antitumor necrosis factor-α antibodies to the surface of adipose-derived stem cell-exosome	Corneal alkali burns	Engineered vesicles	Yu et al[29]
MSCs derived exosomes	Using engineered exosome to modulate ER homeostasis for restoring the function of MSCs	Bone defects in diabetic patients	Engineered vesicles	Liu et al[30]
siRNA encapsulated exosomes	UTMD can enhance the local delivery of exosomes via the cavitation effects	DOX-induced cardiomyopathy	UTMD-assisted exosomal delivery	Chen et al[33]
	The encapsulation of exosomes with ferric ions (Fe3+) and tannic acid		Tannic acid surface modification	Kumar et al[36]
	Tannic acid improves exosome ability to specifically target heart tissue	Heart diseases	Tannic acid surface modification	Shin et al[37]
MSCs derived exosomes	IONP-labeled exosomes intravenous injection followed by the application of a 12 Tesla magnetic field	Clinically relevant model of skin injury	Magnetic nanoparticles targeting	Li et al[39]
Bone marrow MSCs derived exosomes	Magnetic guidance: The retention of injected IONP-MSC-derived NVs within the infarcted heart	Myocardial infarction	Magnetic nanoparticles targeting	Lee et al[40]
Exosomes from neutrophils	Engineered exosomes selectively accumulate at the tumor sites under an external magnetic field	Tumor	Magnetic nanoparticles targeting	Zhang et al[41]
Endogenous extracellular vesicles	Magnetic-guided accumulation of captured CD63-expressing exosomes	Myocardial infarction	Magnetic nanoparticles targeting	Liu et al[42]
ANG peptide-modified engineered exosomes	MNP@BQR@ANG-EXOsiGPX4 platform enriched in the brain under magnetic field	Glioblastoma	Magnetic nanoparticles targeting	Li et al[43]
Milk-derived exosomes	Milk exosomes are good carriers for chemotherapy drugs	Tumor	Oral administration	Munagala et al[47]
Milk-derived exosomes	RSV-loaded milk-derived exosomes to enhance the RSV oral bioavailability	Colon inflammation	Oral administration	Esfahani et al[48]
Yam-derived exosome-like nanovesicles	The orally administered YNVs can be transported through the GI tract and absorbed through the small intestine	Osteoporosis	Oral administration	Hwang et al[49]
Tea leaves-derived exosome-like nanovesicles	Oral administration is significantly less toxic than intravenous administration	Breast cancer	Oral administration	Chen et al[50]
	Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain	Brain inflammatory-related diseases	Intranasal delivery	Zhuang et al[51]
Adipose MSC-EVs	Intranasally administered via intelligent hydrogel	Alzheimer’s disease	Intranasal delivery	Huang et al[52]
Dandelion-derived extracellular vesicle-like nanoparticles	Gelatin methacrylate composite hydrogel	Delayed wound healing caused by bacterial infection	Vesicles patch	Tan et al[58]
MSC derived exosomes	Chitosan-based composite hydrogel dressing	Full-thickness skin defects, diabetic wounds, and burn skin injury	Vesicles patch	Shang et al[59]
	An efficient strategy for delivering exosome-loaded nanoparticles under hypoxic conditions	Poor wound healing following trauma and surgical	Vesicles patch	Han et al[60]
MSCs derived exosomes	HA hydrogel coated with polydopamine and DP7	Burn injuries	Vesicles patch	Yang et al[61]
Curcumin-loaded exosome	An injectable self-healing biphasic hydrogel composed of carboxymethyl chitosan and pullulan	Flap necrosis	Local injection	Liu et al[62]
Exosomes originating from decidual stromal cells	An alginate-based hydrogel scaffold system	Intrauterine adhesion	Local injection	Liang et al[63]
dECM from human umbilical cord MSCs derived exosomes	Exo-dECM hydrogel is a promising therapeutic strategy for treating SCI	SCI	Local injection	Wang et al[64]
Adipose stem cells derived exosomes	Injectable thermosensitive hydrogel system	Androgenic alopecia	Local injection	Xiong et al[65]
Bone marrow MSCs derived exosomes	Exosome-loaded hydrogel microparticles using microfluidic technology	Bone fracture	Local injection	Pan et al[68]
Hybrid exosome-liposome system	Hyaluronic acid-based hydrogel microspheres via microfluidic techniques	Osteoarthritis	Local injection	Chen et al[69]
Adipose stem cells derived exosomes	Clinical efficacy of microneedle-based administration of exosome	Facial skin aging	Microneedles	Park et al[72]
Adipose-derived stem cell extracellular vesicles	A chondroitin sulfate C-based dissolving microneedle	Rheumatoid arthritis	Microneedles	Bui et al[75]
Bone marrow MSCs derived exosomes	A silk fibroin microneedle patch consisting of LPS-pre-Exos and zeolitic imidazolate framework-8	Oral ulcers	Microneedles	Ge et al[76]
MSCs derived exosomes	Gelatin methacrylate microneedles had excellent 3D-Exo loading capacity and enabled continuous 3D-Exo release to maintain effective therapeutic concentrations	Ischemia reperfusion	Microneedles	Zhang et al[77]
Mice breast cancer cell line 4T1 derived exosomes	Nano EXOs loaded within porous microneedles were employed for precise delivery of the STING agonist MSA-2 (MEM) to the tumor site	Tumor	Microneedles	Chen et al[78]
Platelet-derived exosomes	A methacrylate-modified decellularized dermal matrix hydrogel-based microneedle patch	Diabetic wounds	Microneedles	Cao et al[79]
	Microneedle system achieving a balance between mechanical robustness and solubility		Microneedles	Mu et al[80]
MSCs derived exosomes	A novel core-shell microneedle patch	Scarless skin repair	Microneedles	Lyu et al[81]
MSCs derived exosomes	A core-shell microneedle model	Osteoarthritis	Microneedles	Li et al[82]
T cells derived exosomes	A nanovesicle-based delivery platform to promote the efficacy of chemotherapeutic drugs with fewer side effects	Non-small cell lung cancer	Nebulizing	Zheng et al[83]
MSCs derived exosomes	Explored the safety of nebulized haMSC-EVs in healthy volunteers	Preclinical lung injury model	Nebulizing	Shi et al[84]
MSCs derived exosomes	Nebulization of MSC-derived exosomes is a safe, effective, and simple method, and their application at the beginning of treatment may be more beneficial	COVID-19 pneumonia	Nebulizing	Chu et al[85]

3D: Three-dimensional; ANG: Angiotensin; COVID-19: Coronavirus disease 2019; dECM: Decellularized extracellular matrix; DOX: Doxorubicin; ER: Endoplasmic reticulum; EV: Extracellular vesicle; GI: Gastrointestinal; haMSC-EVs: Human adipose-derived mesenchymal stem cell-extracellular vesicles IONP: Iron oxide nanoparticle; LPS: Lipopolysaccharide; MSC: Mesenchymal stem cell; RSV: Resveratrol; SCI: Spinal cord injury; siRNA: Small interfering RNA; UTMD: Ultrasound-mediated microbubble disruption; YNVs: Yam-derived exosome-like nanoparticles.