TY - JOUR
T1 - Repurposing Tamoxifen for Tumor Microenvironment Priming and Enhanced Tumor-Targeted Drug Delivery
AU - Biancacci, Ilaria
AU - De Santis, Daniele
AU - Rama, Elena
AU - Benderski, Karina
AU - Momoh, Jeffrey
AU - Pohlberger, Robert
AU - Moeckel, Diana
AU - Kaps, Leonard
AU - Rijcken, Cristianne J.F.
AU - Prakash, Jai
AU - Thewissen, Marielle
AU - Kiessling, Fabian
AU - Shi, Yang
AU - Peña, Quim
AU - Sofias, Alexandros Marios
AU - Consolino, Lorena
AU - Lammers, Twan
N1 - Funding Information:
The authors gratefully acknowledge financial support by the European Research Council (ERC‐CoG: Meta‐Targeting 864121), by the German Research Foundation (DFG: GRK2375 (grant number 331065168), LA‐2937/4‐1 and SFB1066), and by the German Federal Ministry of Research and Education (BMBF: Gezielter Wirkstofftransport; PP‐TNBC, Project No. 16GW0319K). Support by the Two‐Photon Imaging Core Facility at the Interdisciplinary Center for Clinical Research (IZKF) at the Faculty of Medicine at RWTH Aachen University is also acknowledged. The table of contents image was created by using BioRender.com.
Publisher Copyright:
© 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.
PY - 2023/11
Y1 - 2023/11
N2 - The dense stromal matrix in fibrotic tumors hinders tumor-targeted drug delivery. Tamoxifen (TMX), an estrogen receptor modulator that is clinically used for the treatment of breast cancer, is shown to reprogram the tumor microenvironment (TME) and to alleviate desmoplasia. It is investigated if TMX, administered in free and nano-formulated form, can be repurposed as a TME remodeling agent to improve tumor accumulation of nano-formulations in pancreatic ductal adenocarcinoma and triple-negative breast cancer mouse models, evaluated using clinical-stage Cy7-labeled core-crosslinked polymeric micelles (CCPM). Under control conditions, higher levels of Cy7-CCPM are found in PANC-1 tumors (16.7% ID g−1 at 48 h post i.v. injection) than in 4T1 tumors (11.0% ID g−1). In both models, free and nano-formulated TMX failed to improve CCPM delivery. These findings are congruent with the results from histopathological immunofluorescence analysis of tumor tissue, which indicate that TMX treatment does not significantly change vascularization, perfusion, macrophage infiltration, collagen density, and collagen fiber thickness. Altogether, these results demonstrate that in PANC-1 and 4T1 mouse models, TMX treatment does not contribute to beneficial TME priming and enhanced tumor-targeted drug delivery.
AB - The dense stromal matrix in fibrotic tumors hinders tumor-targeted drug delivery. Tamoxifen (TMX), an estrogen receptor modulator that is clinically used for the treatment of breast cancer, is shown to reprogram the tumor microenvironment (TME) and to alleviate desmoplasia. It is investigated if TMX, administered in free and nano-formulated form, can be repurposed as a TME remodeling agent to improve tumor accumulation of nano-formulations in pancreatic ductal adenocarcinoma and triple-negative breast cancer mouse models, evaluated using clinical-stage Cy7-labeled core-crosslinked polymeric micelles (CCPM). Under control conditions, higher levels of Cy7-CCPM are found in PANC-1 tumors (16.7% ID g−1 at 48 h post i.v. injection) than in 4T1 tumors (11.0% ID g−1). In both models, free and nano-formulated TMX failed to improve CCPM delivery. These findings are congruent with the results from histopathological immunofluorescence analysis of tumor tissue, which indicate that TMX treatment does not significantly change vascularization, perfusion, macrophage infiltration, collagen density, and collagen fiber thickness. Altogether, these results demonstrate that in PANC-1 and 4T1 mouse models, TMX treatment does not contribute to beneficial TME priming and enhanced tumor-targeted drug delivery.
KW - drug delivery
KW - nanomedicine
KW - polymeric micelles
KW - tamoxifen
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=85165240506&partnerID=8YFLogxK
U2 - 10.1002/adtp.202300098
DO - 10.1002/adtp.202300098
M3 - Article
AN - SCOPUS:85165240506
SN - 2366-3987
VL - 6
JO - Advanced Therapeutics
JF - Advanced Therapeutics
IS - 11
M1 - 2300098
ER -
