BACKGROUND: Exosomes are membrane-enclosed extracellular vesicles implicated in cell-cell communication. Exosomes contain proteins, mRNAs, non-coding RNAs (miRNAs and lncRNAs) and lipids that are derived from producing cells. These nano-sized vesicles are present in biofluids including blood, urine, saliva, amniotic fluid, semen and conditioned media of cultured cells. METHODS: This review summarizes current progress on the strategies of development of diagnostic biomarkers and drug loading onto exosomes for overcoming cancer progression. RESULTS: A number of studies indicate that the exosome appears to be a key player in tissue repair and regeneration of in a number of animal disease models. In addition, alterations of the molecular profiles in exosomes are known to be correlated with the disease progression including cancer, suggesting their usefulness in disease diagnosis and prognosis. Studies utilizing engineered exosomes either by chemical or biological methods have demonstrated promising results in a number of animal models with cancer. CONCLUSION: Understanding the molecular and cellular properties of exosomes offer benefits for cancer diagnosis by liquid biopsy and for their application in therapeutic drug delivery systems. Studies have shown that genetic or molecular engineering of exosomes augmented their target specificity and anticancer activity with less toxicity. Thus, deeper understanding of exosome biology will facilitate their therapeutic potential as an innovative drug delivery system for cancer.
Amniotic Fluid ; Biology ; Biomarkers ; Biopsy ; Cells, Cultured ; Culture Media, Conditioned ; Diagnosis ; Disease Models, Animal ; Disease Progression ; Drug Delivery Systems ; Exosomes ; Extracellular Vesicles ; Female ; Models, Animal ; Prognosis ; Regeneration ; RNA, Messenger ; RNA, Untranslated ; Saliva ; Semen ; Sensitivity and Specificity

Objective: We used paclitaxel and cisplatin, known to be effective in intraperitoneal chemotherapy, in a novel prototype of rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) and evaluated the pharmacokinetics, tissue concentrations, and toxicities in a pig model. Methods: We developed RIPAC, including the nozzle with the conical pendulum motion, and used 10% of intravenous doses of paclitaxel and cisplatin. We used high-performance liquid chromatography followed by tandem mass spectrometry to analyze serum and tissue concentrations. We applied a non-compartment model to study pharmacokinetics to analyze the time-dependent serum concentrations measured before RIPAC to 48 hours. We evaluated the difference in tissue concentrations between twelve peritoneal regions by the modified peritoneal cancer index. For evaluating toxicities, we observed hepatic and renal function until 4 days after RIPAC. Results: Six pigs underwent RIPAC using paclitaxel (n=3) and cisplatin (n=3). The peak serum concentration (Cmax) and the area under the curve were higher for cisplatin, while the time to the peak serum concentration (Tmax) was longer for paclitaxel. Moreover, the parietal peritoneum showed higher tissue concentrations than the visceral peritoneum, and the ratio of tissue to serum concentrations using Cmax was higher for paclitaxel (172.2–6,237.9) than for cisplatin (0.1–9.3). However, there were no renal and hepatic toxicities after RIPAC with paclitaxel or cisplatin. Conclusion Delayed absorption of paclitaxel sprayed by RIPAC into the peritoneum to the bloodstream may lead to higher tissue concentrations at different regions and lower serum concentrations than cisplatin.