Drug-loaded exosomal preparations from different cell types exhibit distinctive loading capability, yield, and antitumor efficacies: a comparative analysis

Abstract

BackgroundDespite tremendous advancement, cancer still remains one of the leading causes of death worldwide. Inefficiency of current drug delivery regimens is one important factor that limits the therapeutic efficacy of existing drugs, thus contributing to cancer mortality. To address this limitation, synthetic nanotechnology-based delivery systems have been developed; however, they raise concern of inducing adverse immunogenic reactions. Exosomes (Exos) are nonimmunogenic nanosized vesicles that have received significant attention as efficient drug delivery system.MethodsDrug loading in Exos were achieved by incubating different cell types viz pancreatic cancer cells (PCCs), pancreatic stellate cells (PSCs), and macrophages (MØs) with Doxorubicin (DOX). Differential ultracentrifugation was performed to isolate exosome and their size was determined by dynamic light scattering analysis. The efficacy of drug packaging into Exos was evaluated by HPLC. Flow cytometry was performed to examine the apoptosis. Cell viability was determined using the WST-1 assay.ResultsPCCs shed the most Exos and were the most efficient in drug loading followed by MØs and PSCs as examined by HPLC quantification. However, when compared for antitumor efficacy, MØ-derived Exos loaded with DOX (MØ-Exo-DOX) showed highest activity followed by PSCs and PCCs.ConclusionThese varying antitumor activities likely resulted from nondrug contents of Exos since we did not observe any significant differences in their uptake by the cancer cells. Altogether, our data suggest that donor cell-specific differences exist in Exos, which could influence their utility as drug carrier for therapeutic purposes.

Hypoxia alters the release and size distribution of extracellular vesicles in pancreatic cancer cells to support their adaptive survival

“…Although initially believed to serve as trash bags to get rid of unwanted cellular material, EVs are now established as functional entities that are capable of altering the properties of the recipient cells through transfer of bioactive cargo. 18,34 Interestingly, we also observed cell line-specific differences in the level of induction of EVs release. 18,19,34 F I G U R E 6 HIF-1α mediates the effect of hypoxia on the release of extracellular vesicles (EVs) and their effect on hypoxic survival of pancreatic cancer cells.…”

<p>Exosome: A Review of Its Classification, Isolation Techniques, Storage, Diagnostic and Targeted Therapy Applications</p>

“…As a result, different therapeutic effects may be produced. Kanchanapally et al 34 used co-incubation to successfully load doxorubicin (DOX) onto pancreatic stellate cells (PSCs), pancreatic cancer cells (PCCs) and macro-phage-derived exosomes. By contrast, exosomes derived from PSCs have the highest yield and high drug loading rate, while macrophagederived exosomes have the strongest antitumor activity, indicating the specificity of exosomes from different sources.…”

Extracellular Vesicles in the Development of Cancer Therapeutics

“…Indeed, experimental evidence has been provided to show that drug loading efficiency of sEVs derived from pancreatic stellate cells (PSCs), pancreatic cancer cells (PCCs), and macrophages significantly differ when doxorubicin was simply incubated with the sEVs, with those from PCCs being most efficient. However, the doxorubicin-loaded macrophage sEVs are most effective in killing cancer cells, indicating that higher loading capacity does not equal to high anticancer activity of the drug-loaded sEVs [ 127 ]. This implies that both the biological source of the sEVs and the drug loading efficiency need to be evaluated when sEVs are applied as drug carriers for cancer therapy.…”