GelMA, Click-Chemistry Gelatin and Bioprinted Polyethylene Glycol-Based Hydrogels as 3D Ex Vivo Drug Testing Platforms for Patient-Derived Breast Cancer Organoids

被引：31

作者：

Bock, Nathalie ^{[1
,2
,3
,4
]}

Forouz, Farzaneh ^{[1
,4
]}

Hipwood, Luke ^{[1
,3
,5
]}

Clegg, Julien ^{[3
,5
,6
,7
,8
]}

Jeffery, Penny ^{[1
,6
]}

Gough, Madeline ^{[9
]}

van Wyngaard, Tirsa ^{[6
,10
]}

Pyke, Christopher ^{[9
]}

Adams, Mark N. ^{[1
,7
,11
]}

Bray, Laura J. ^{[3
,6
,7
]}

Croft, Laura ^{[1
,6
,11
]}

Thompson, Erik W. ^{[1
,6
]}

Kryza, Thomas ^{[9
]}

Meinert, Christoph ^{[3
,5
]}

机构：

[1] Queensland Univ Technol QUT, Translat Res Inst TRI, Fac Hlth, Sch Biomed Sci, Brisbane, Qld 4000, Australia

[2] Max Planck Queensland Ctr, Brisbane, Qld 4059, Australia

[3] QUT, Ctr Biomed Technol, Brisbane, Qld 4059, Australia

[4] QUT, Australian Prostate Canc Res Ctr APCRC Q, Brisbane, Qld 4102, Australia

[5] Gelomics Pty Ltd, Brisbane, Qld 4059, Australia

[6] Ctr Personalised Anal Canc CPAC, Brisbane, Qld 4102, Australia

[7] QUT, ARC Training Ctr Cell & Tissue Engn Technol, Brisbane, Qld 4059, Australia

[8] QUT, Sch Mech Med & Proc Engn, Brisbane, Qld 4000, Australia

[9] Mater Res Inst, Brisbane, Qld 4102, Australia

[10] Princess Alexandra Hosp, Breast & Endocrine Surg, Woolloongabba, Qld 4102, Australia

[11] Ctr Genom & Personalised Hlth, Brisbane, Qld 4000, Australia

来源：

PHARMACEUTICS | 2023年 / 15卷 / 01期

关键词：

3D cancer model; patient-derived organoid; hydrogel; GelMA; gelatin; polyethylene glycol; extracellular matrix; tumor microenvironment; doxorubicin; adriamycin; paclitaxel; EP31670; breast cancer; drug resistance; precision medicine; TUMOR HETEROGENEITY; PROSTATE; DOXORUBICIN; MODELS; CHEMOTHERAPY; PACLITAXEL; XENOGRAFT; GROWTH;

D O I：

10.3390/pharmaceutics15010261

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel((R))) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease's extracellular matrix. Here, we encapsulated patient-derived breast cancer cells in bioprinted polyethylene glycol-derived hydrogels (PEG), functionalized with adhesion peptides (RGD, GFOGER and DYIGSR) and gelatin-derived hydrogels (gelatin methacryloyl; GelMA and thiolated-gelatin crosslinked with PEG-4MAL; GelSH). Within ranges of BCa stiffnesses (1-6 kPa), GelMA, GelSH and PEG-based hydrogels successfully supported the growth and organoid formation of HR+,-/HER2+,- primary cancer cells for at least 2-3 weeks, with superior organoid formation within the GelSH biomaterial (up to 268% growth after 15 days). BCa organoids responded to doxorubicin, EP31670 and paclitaxel treatments with increased IC50 concentrations on organoids compared to 2D cultures, and highest IC50 for organoids in GelSH. Cell viability after doxorubicin treatment (1 mu M) remained >2-fold higher in the 3D gels compared to 2D and doxorubicin/paclitaxel (both 5 mu M) were similar to 2.75-3-fold less potent in GelSH compared to PEG hydrogels. The data demonstrate the potential of hydrogel matrices as easy-to-use and effective preclinical tools for therapy assessment in patient-derived breast cancer organoids.

引用

页数：23

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