TY - JOUR
T1 - Preferential uptake of antibody targeted calcium phosphosilicate nanoparticles by metastatic triple negative breast cancer cells in co-cultures of human metastatic breast cancer cells plus bone osteoblasts
AU - Bussard, Karen M.
AU - Gigliotti, Christopher M.
AU - Adair, Bernadette M.
AU - Snyder, Jenna M.
AU - Gigliotti, Nicholas T.
AU - Loc, Welley S.
AU - Wilczynski, Zachary R.
AU - Liu, Zi Kui
AU - Meisel, Kacey
AU - Zemanek, Cecilia
AU - Mastro, Andrea M.
AU - Shupp, Alison B.
AU - McGovern, Christopher
AU - Matters, Gail L.
AU - Adair, James H.
N1 - Funding Information:
Acknowledgments: This study was funded in part by National Institutes of Health (NIH) grants R01CA167535 (GLM and JHA) and R21CA170121 (GLM) from the National Cancer Institute (NCI), NIH, NCI CA178177-05 (KMB); Pennsylvania Department of Health, Tobacco CURE funds SAP#4100072562 (GLM and JHA); and The Pennsylvania Breast Cancer Coalition (KMB). CMG and WSL were supported, in part, by grants UL1 TR000127 and TL1 TR000125 from the National Center for Advancing Translational Sciences (NCATS). The Department of Materials Science and Engineering at Penn State disclaims responsibility for any analyses, interpretations or conclusions. Penn State Research Foundation has licensed CPSNP technology to Keystone Nano, Inc. (PA, USA). JHA is a co-founder of PandreaBio (formerly Keystone Nano) and CSO. All other authors declare no conflicts of interest.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/6
Y1 - 2021/6
N2 - Calcium phosphosilicate nanoparticles (CPSNPs) are bioresorbable nanoparticles that can be bioconjugated with targeting molecules and encapsulate active agents and deliver them to tumor cells without causing damage to adjacent healthy tissue. Data obtained in this study demonstrated that an anti-CD71 antibody on CPSNPs targets these nanoparticles and enhances their internalization by triple negative breast cancer cells in-vitro. Caspase 3,7 activation, DNA damage, and fluorescent microscopy confirmed the apoptotic breast cancer response caused by targeted anti-CD71-CPSNPs encapsulated with gemcitabine monophosphate, the active metabolite of the chemotherapeutic gemcitabine used to treat cancers including breast and ovarian. Targeted anti-CD71-CPSNPs encapsulated with the fluorophore, Rhodamine WT, were preferentially internalized by breast cancer cells in co-cultures with osteoblasts. While osteoblasts partially internalized anti-CD71-GemMP-CPSNPs, their cell growth was not affected. These results suggest that CPSNPs may be used as imaging tools and selective drug delivery systems for breast cancer that has metastasized to bone.
AB - Calcium phosphosilicate nanoparticles (CPSNPs) are bioresorbable nanoparticles that can be bioconjugated with targeting molecules and encapsulate active agents and deliver them to tumor cells without causing damage to adjacent healthy tissue. Data obtained in this study demonstrated that an anti-CD71 antibody on CPSNPs targets these nanoparticles and enhances their internalization by triple negative breast cancer cells in-vitro. Caspase 3,7 activation, DNA damage, and fluorescent microscopy confirmed the apoptotic breast cancer response caused by targeted anti-CD71-CPSNPs encapsulated with gemcitabine monophosphate, the active metabolite of the chemotherapeutic gemcitabine used to treat cancers including breast and ovarian. Targeted anti-CD71-CPSNPs encapsulated with the fluorophore, Rhodamine WT, were preferentially internalized by breast cancer cells in co-cultures with osteoblasts. While osteoblasts partially internalized anti-CD71-GemMP-CPSNPs, their cell growth was not affected. These results suggest that CPSNPs may be used as imaging tools and selective drug delivery systems for breast cancer that has metastasized to bone.
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U2 - 10.1016/j.nano.2021.102383
DO - 10.1016/j.nano.2021.102383
M3 - Article
C2 - 33722692
AN - SCOPUS:85103758624
SN - 1549-9634
VL - 34
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
M1 - 102383
ER -