Table 3 Summary of studies investigating EVs as drug delivery and the therapeutic targets in pancreatic cancer

MSCs

Paclitaxel

MSCs package and deliver active drugs through their MVs with a higher cell-target specificity and anticancer cytotoxicity

[120]

MSCs

Paclitaxel

EVs derived from MSCs pre-treated with paclitaxel against pancreatic cancer cells, showing a significant proliferation inhibition and direct anticancer activity

[145]

Macrophages

Doxorubicin

Macrophages-derived EVs-doxorubicin preparation induces greater apoptosis and higher antitumor activity in cancer cells compared to those derived from pancreatic cancer or PSCs

[146]

PDAC

Gemcitabine

Autologous exosomes facilitate cellular uptake of GEM and contributed to increased cytotoxic effect of GEM. Autologous exosomes also show targeting ability to pancreatic cancer in biodistribution study

[147]

MSCs

KrasG12D siRNA

The are expected to be presented by March 2022

NCT03608631

CAFs

miR-146a

The EVs of CAFs exposed to gemcitabine results in increasing expression of Snail (SNAI1) as well as the Snail target, microRNA-146a, which promote pancreatic cancer cells drug resistance

[67]

CAFs

miR-106b

MiR-106b can be directly transferred from CAFs to pancreatic cancer cells through EVs, which promotes gemcitabine resistance of cancer cells by targeting TP53INP1

[68]

PDAC

miR-155

Pancreatic cancer cells secrete EVs containing miR-155 to impact tumor-adjacent normal fibroblasts to convert them into CAFs, thus increasing drug resistance

[72]

Macrophage

miR-365

Transfer of miR-365 in macrophage-derived EVs induces resistance of pancreatic cancer cells to gemcitabine

[91]

PDAC

EphA2

EVs derived from chemo-resistant pancreatic cells confer gemcitabine resistance to sensitive cells via an EphA2-dependent mechanism

[151]