Large-scale generation of cell-derived nanovesicles. Nanoscale 6:12056–12064
39. Grossman JG, Nywening TM, Belt B,
Ahlers M, Hawkins WG, Strasberg SM, Goedegebuure PS, Linehan D, Fields RC (2017)
Targeting inflammatory monocytes in human
metastatic colorectal cancer. J Clin Oncol
35:605–605
40. Goh WJ, Lee CK, Zou S, Woon EC, Czarny B,
Pastorin G (2017) Doxorubicin-loaded cellderived nanovesicles: an alternative targeted
approach for anti-tumor therapy. Int J
Nanomed 12:2759–2767
41. Goh WJ, Zou S, Lee CK, Ou Y-H, Wang J-W,
Czarny B, Pastorin G (2018) EXOPLEXs: chimeric drug delivery platform from the fusion of
cell-derived nanovesicles and liposomes. Biomacromolecules 19:22–30
42. Fritze A, Hens F, Kimpfler A, Schubert R,
Peschka-Su ¨ss R (2006) Remote loading of
doxorubicin into liposomes driven by a transmembrane phosphate gradient. Biochim Biophys Acta Biomembr 1758:1633–1640
43. Sun D, Zhuang X, Xiang X, Liu Y, Zhang S,
Liu C, Barnes S, Grizzle W, Miller D, Zhang
H-G (2010) A novel nanoparticle drug delivery system: the anti-inflammatory activity of
curcumin is enhanced when encapsulated in
exosomes. Mol Ther 18:1606–1614
44. Takahashi Y, Nishikawa M, Shinotsuka H,
Matsui Y, Ohara S, Imai T, Takakura Y
(2013) Visualization and in vivo tracking of
the exosomes of murine melanoma B16-BL6
cells in mice after intravenous injection. J Biotechnol 165:77–84
45. Smyth T, Kullberg M, Malik N, Smith-Jones P,
Graner MW, Anchordoquy TJ (2015) Biodistribution and delivery efficiency of unmodified
tumor-derived exosomes. J Control Release
199:145–155
46. Abe M, Havre PA, Urasaki Y, Ohnuma K,
Morimoto C, Dang LH, Dang NH (2011)
Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines. BMC
Cancer 11:51
47. Ruutu M, Johansson B, Grenman R,
Syrj€ anen K, Syrj€ anen S (2004) Effect of confluence state and passaging on global cancer gene
expression pattern in oral carcinoma cell lines.
Anticancer Res 24:2627–2631
48. Saeki K, Yuo A, Kato M, Miyazono K, Yazaki Y,
Takaku F (1997) Cell density-dependent apoptosis in HL-60 cells, which is mediated by an
unknown soluble factor, is inhibited by transforming growth factor beta1 and overexpression of Bcl-2. J Biol Chem 272:20003–20010
49. Fang C-Y, Wu C-C, Fang C-L, Chen W-Y,
Chen C-L (2017) Long-term growth comparison studies of FBS and FBS alternatives in six
head and neck cell lines. PLoS One. https://
doi.org/10.1371/journal.pone.0178960
50. Shelke GV, L€ asser C, Gho YS, Lo ¨tvall J (2014)
Importance of exosome depletion protocols to
eliminate functional and RNA-containing
extracellular vesicles from fetal bovine serum.
J Extracell Vesicles 3:24783
51. Li P, Kaslan M, Lee SH, Yao J, Gao Z (2017)
Progress in exosome isolation techniques.
Theranostics 7:789–804
52. Witwer KW, Buza ´s EI, Bemis LT et al (2013)
Standardization of sample collection, isolation
and analysis methods in extracellular vesicle
research. J Extracell Vesicles. https://doi.org/
10.3402/jev.v2i0.20360
53. Rhodes DG, Laue TM (2009) Determination
of protein purity. In: Methods enzymol. Academic Press, New York, pp 677–689
54. Lu GW, Gao P (2010) Emulsions and microemulsions for topical and transdermal drug
delivery. In: Personal Care & Cosmetic Technology, Handbook of Non-invasive Drug
Delivery Systems, VS. Kulkarni (ed), William
Andrew Publishing, pp 59–94, ISBN
9780815520252, https://doi.org/10.1016/
B978-0-8155-2025-2.10003-4. (http://www.
sciencedirect.com/science/article/pii/
B9780815520252100034)
55. Gumustas M, Sengel-Turk CT, Gumustas A,
Ozkan SA, Uslu B (2017) Effect of polymerbased nanoparticles on the assay of antimicrobial drug delivery systems. In: Multifunctional
systems for combined delivery, biosensing and
diagnostics (pp 67–108)
56. Malvern Instruments (2009) Technical Manual: Zetasizer Nano
57. Lobb RJ, Becker M, Wen SW, Wong CSF,
Wiegmans AP, Leimgruber A, Mo ¨ller A
(2015) Optimized exosome isolation protocol
for cell culture supernatant and human plasma.
J Extracell Vesicles 4:27031
58. Zhu L, Gangadaran P, Kalimuthu S, Oh JM,
Baek SH, Jeong SY, Lee S-W, Lee J, Ahn B-C
(2018) Novel alternatives to extracellular
vesicle-based
immunotherapy—exosome
mimetics derived from natural killer cells. Artif
Cells Nanomed Biotechnol 46:S166–S179
59. Emam SE, Ando H, Selim A et al (2018) A
novel strategy to increase the yield of exosomes
(extracellular vesicles) for an expansion of basic
research. Biol Pharm Bull 41:733–742
60. Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MM (2015) Active loading into extracellular vesicles significantly improves the cellular
Exosome-Mimetics For Drug Delivery
169
39. Grossman JG, Nywening TM, Belt B,
Ahlers M, Hawkins WG, Strasberg SM, Goedegebuure PS, Linehan D, Fields RC (2017)
Targeting inflammatory monocytes in human
metastatic colorectal cancer. J Clin Oncol
35:605–605
40. Goh WJ, Lee CK, Zou S, Woon EC, Czarny B,
Pastorin G (2017) Doxorubicin-loaded cellderived nanovesicles: an alternative targeted
approach for anti-tumor therapy. Int J
Nanomed 12:2759–2767
41. Goh WJ, Zou S, Lee CK, Ou Y-H, Wang J-W,
Czarny B, Pastorin G (2018) EXOPLEXs: chimeric drug delivery platform from the fusion of
cell-derived nanovesicles and liposomes. Biomacromolecules 19:22–30
42. Fritze A, Hens F, Kimpfler A, Schubert R,
Peschka-Su ¨ss R (2006) Remote loading of
doxorubicin into liposomes driven by a transmembrane phosphate gradient. Biochim Biophys Acta Biomembr 1758:1633–1640
43. Sun D, Zhuang X, Xiang X, Liu Y, Zhang S,
Liu C, Barnes S, Grizzle W, Miller D, Zhang
H-G (2010) A novel nanoparticle drug delivery system: the anti-inflammatory activity of
curcumin is enhanced when encapsulated in
exosomes. Mol Ther 18:1606–1614
44. Takahashi Y, Nishikawa M, Shinotsuka H,
Matsui Y, Ohara S, Imai T, Takakura Y
(2013) Visualization and in vivo tracking of
the exosomes of murine melanoma B16-BL6
cells in mice after intravenous injection. J Biotechnol 165:77–84
45. Smyth T, Kullberg M, Malik N, Smith-Jones P,
Graner MW, Anchordoquy TJ (2015) Biodistribution and delivery efficiency of unmodified
tumor-derived exosomes. J Control Release
199:145–155
46. Abe M, Havre PA, Urasaki Y, Ohnuma K,
Morimoto C, Dang LH, Dang NH (2011)
Mechanisms of confluence-dependent expression of CD26 in colon cancer cell lines. BMC
Cancer 11:51
47. Ruutu M, Johansson B, Grenman R,
Syrj€ anen K, Syrj€ anen S (2004) Effect of confluence state and passaging on global cancer gene
expression pattern in oral carcinoma cell lines.
Anticancer Res 24:2627–2631
48. Saeki K, Yuo A, Kato M, Miyazono K, Yazaki Y,
Takaku F (1997) Cell density-dependent apoptosis in HL-60 cells, which is mediated by an
unknown soluble factor, is inhibited by transforming growth factor beta1 and overexpression of Bcl-2. J Biol Chem 272:20003–20010
49. Fang C-Y, Wu C-C, Fang C-L, Chen W-Y,
Chen C-L (2017) Long-term growth comparison studies of FBS and FBS alternatives in six
head and neck cell lines. PLoS One. https://
doi.org/10.1371/journal.pone.0178960
50. Shelke GV, L€ asser C, Gho YS, Lo ¨tvall J (2014)
Importance of exosome depletion protocols to
eliminate functional and RNA-containing
extracellular vesicles from fetal bovine serum.
J Extracell Vesicles 3:24783
51. Li P, Kaslan M, Lee SH, Yao J, Gao Z (2017)
Progress in exosome isolation techniques.
Theranostics 7:789–804
52. Witwer KW, Buza ´s EI, Bemis LT et al (2013)
Standardization of sample collection, isolation
and analysis methods in extracellular vesicle
research. J Extracell Vesicles. https://doi.org/
10.3402/jev.v2i0.20360
53. Rhodes DG, Laue TM (2009) Determination
of protein purity. In: Methods enzymol. Academic Press, New York, pp 677–689
54. Lu GW, Gao P (2010) Emulsions and microemulsions for topical and transdermal drug
delivery. In: Personal Care & Cosmetic Technology, Handbook of Non-invasive Drug
Delivery Systems, VS. Kulkarni (ed), William
Andrew Publishing, pp 59–94, ISBN
9780815520252, https://doi.org/10.1016/
B978-0-8155-2025-2.10003-4. (http://www.
sciencedirect.com/science/article/pii/
B9780815520252100034)
55. Gumustas M, Sengel-Turk CT, Gumustas A,
Ozkan SA, Uslu B (2017) Effect of polymerbased nanoparticles on the assay of antimicrobial drug delivery systems. In: Multifunctional
systems for combined delivery, biosensing and
diagnostics (pp 67–108)
56. Malvern Instruments (2009) Technical Manual: Zetasizer Nano
57. Lobb RJ, Becker M, Wen SW, Wong CSF,
Wiegmans AP, Leimgruber A, Mo ¨ller A
(2015) Optimized exosome isolation protocol
for cell culture supernatant and human plasma.
J Extracell Vesicles 4:27031
58. Zhu L, Gangadaran P, Kalimuthu S, Oh JM,
Baek SH, Jeong SY, Lee S-W, Lee J, Ahn B-C
(2018) Novel alternatives to extracellular
vesicle-based
immunotherapy—exosome
mimetics derived from natural killer cells. Artif
Cells Nanomed Biotechnol 46:S166–S179
59. Emam SE, Ando H, Selim A et al (2018) A
novel strategy to increase the yield of exosomes
(extracellular vesicles) for an expansion of basic
research. Biol Pharm Bull 41:733–742
60. Fuhrmann G, Serio A, Mazo M, Nair R, Stevens MM (2015) Active loading into extracellular vesicles significantly improves the cellular
Exosome-Mimetics For Drug Delivery
169