Hyaluronic acid-based hydrogels as 3D matrices for in vitro evaluation of chemotherapeutic drugs using poorly adherent prostate cancer cells.
The current investigation aimed to develop a biomimetic, three-dimensional (3D) culture system for poorly adherent bone metastatic prostate cancer cells (C4-2B) for use as an in vitro platform for anti-cancer drug screening. To this end, hyaluronic acid (HA) derivatives carrying complementary aldehyde (HAALD) and hydrazide (HAADH) groups were synthesized and characterized. In situ encapsulation of C4-2B cells was achieved by simple mixing of HAALD and HAADH in the presence of the cells. Unlike two-dimensional (2D) monolayer culture in which cells adopt an atypical spread morphology, cells residing in the HA matrix formed distinct clustered structures which grew and merged, reminiscent of real tumors. Anti-cancer drugs added to the media surrounding the cell/gel construct diffused into the gel and killed the embedded cells. The HA hydrogel system was used successfully to test the efficacy of anti-cancer drugs including camptothecin, docetaxel, and rapamycin, alone and in combination, including specificity, dose and time responses. Responses of cells to anti-neoplastics differed between the 3D HA hydrogel and 2D monolayer systems. We suggest that the data obtained from 3D HA systems is superior to that from conventional 2D monolayers as the 3D system better reflects the bone metastatic microenvironment of the cancer cells.
Gurski
Lisa A
LA
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
Jha
Amit K
AK
Zhang
Chu
C
Jia
Xinqiao
X
Farach-Carson
Mary C
MC
D000447:Aldehydes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion; D018929:Cell Culture Techniques / Q000379:methods; D004058:Diffusion; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006834:Hydrazines / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020100:Hydrogels / Q000737:chemistry*; D008297:Male; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D000447:Aldehydes; D000970:Antineoplastic Agents; D006834:Hydrazines; D020100:Hydrogels; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C029424:hydrazine; D006820:Hyaluronic Acid
Acta Biomater. 2008 Mar;4(2):256-63
17936097
Nat Rev Drug Discov. 2007 Jun;6(6):455-63
17541418
Mol Pharm. 2008 Sep-Oct;5(5):849-62
18680382
Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6315-20
16606824
Fed Proc. 1958 Dec;17(4):1075-7
13619775
Semin Cancer Biol. 2005 Oct;15(5):365-77
15975824
Matrix Biol. 2008 Jul;27(6):573-585
18411046
Cell. 2007 Aug 24;130(4):601-10
17719539
Nat Methods. 2007 Oct;4(10):855-60
17767164
Acc Chem Res. 2008 Jan;41(1):139-48
17655274
Nat Rev Cancer. 2006 Oct;6(10):813-23
16990858
Int J Pharm. 2004 Dec 9;287(1-2):13-9
15541907
J Biol Chem. 2002 Oct 18;277(42):39703-12
12145287
Biotechnol Adv. 2007 Nov-Dec;25(6):537-57
17716848
Acta Histochem. 2006;108(2):141-7
16713618
Ann N Y Acad Sci. 1995 Dec 29;770:70-8
8597383
Macromolecules. 2009;42(2):537-546
20046226
Int J Pharm. 2001 Feb 1;213(1-2):25-9
11165091
Semin Cancer Biol. 2008 Aug;18(4):244-50
18534864
J Pharmacokinet Pharmacodyn. 2007 Jun;34(3):373-400
17431753
Biomaterials. 2004 Aug;25(19):4797-804
15120526
Biomacromolecules. 2005 Mar-Apr;6(2):1132-9
15762686
Am J Pathol. 2009 Mar;174(3):1027-36
19218337
J Control Release. 2008 Jul 14;129(2):144-50
18538885
Expert Opin Pharmacother. 2008 Aug;9(11):1969-79
18627334
Expert Rev Mol Med. 2008 Mar 06;10:e7
18321396
Biochim Biophys Acta. 2004 Jul 5;1692(2-3):103-19
15246682
Front Biosci. 2007 May 01;12:3273-86
17485298
J Cell Biochem. 2009 Jun 1;107(3):473-81
19347904
In Vitro Cell Dev Biol Anim. 2006 Sep-Oct;42(8-9):242-7
17163781
J Natl Cancer Inst. 2006 Aug 16;98(16):1118-28
16912264
J Nat Prod. 2004 Feb;67(2):232-44
14987065
FEBS Lett. 2002 Sep 25;528(1-3):101-8
12297287
Cancer Res. 1999 Jun 15;59(12):2891-7
10383151
Prostate. 2000 Jul 1;44(2):91-103 Jul 1;44(2)
10881018
J Control Release. 2008 May 8;127(3):231-8
18384903
Nat Rev Cancer. 2005 Sep;5(9):675-88
16148884
J Biol Chem. 2003 Aug 8;278(32):29420-34
12748184
Anticancer Res. 2004 Jul-Aug;24(4):2169-77
15330157
Bioorg Med Chem Lett. 1999 Jan 18;9(2):295-300
10021948
Prostate. 2008 Jun 1;68(8):861-71
18361409
Clin Cancer Res. 2007 Jun 1;13(11):3109-14
17545512
Biomacromolecules. 2006 Dec;7(12):3336-44
17154461