In clinical practice, we noticed that triple negative breast cancer (TNBC) patients had higher shear-wave elasticity (SWE) stiffness than non-TNBC patients and a higher α-SMA expression was found in TNBC tissues than the non-TNBC tissues. Moreover, SWE stiffness also shows a clear correlation to neoadjuvant response efficiency. To elaborate this phenomenon, TNBC cell membrane-modified polylactide acid-glycolic acid (PLGA) nanoparticle was fabricated to specifically deliver artesunate to regulate SWE stiffness through inhibiting CAFs functional status. As tested in MDA-MB-231 and E0771 orthotopic tumor models, CAFs functional status inhibited by 231M-ARS@PLGA nanoparticles (231M-AP NPs) had reduced the SWE stiffness as well as attenuated hypoxia of tumor as tumor soil loosening agent which amplified the antitumor effects of paclitaxel and PD1 inhibitor. Single-cell sequencing indicated that the two main CAFs (extracellular matrix and wound healing CAFs) that produces extracellular matrix could influence the tumor SWE stiffness as well as the antitumor effect of drugs. Further, biomimetic nanoparticles inhibited CAFs function could attenuate tumor hypoxia by increasing proportion of inflammatory blood vessels and oxygen transport capacity. Therefore, our finding is fundamental for understanding the role of CAFs on affecting SWE stiffness and drugs antitumor effects, which can be further implied in the potential clinical theranostic predicting in neoadjuvant therapy efficacy through non-invasive analyzing of SWE imaging.
|DOI - pysyväislinkit|
|Tila||Julkaistu - huhtik. 2023|
|OKM-julkaisutyyppi||A1 Julkaistu artikkeli, soviteltu|
SormenjälkiSukella tutkimusaiheisiin 'Biomimetic nanoparticles drive the mechanism understanding of shear-wave elasticity stiffness in triple negative breast cancers to predict clinical treatment'. Ne muodostavat yhdessä ainutlaatuisen sormenjäljen.
Åbo Akademi Functional Printing Center
Martti Toivakka (PI), Jessica Rosenholm (PI), Nicklas Anttu (PI), Johan Bobacka (PI), Tan Phat Huynh (PI), Jouko Peltonen (PI), Xiaoju Wang (PI), Carl-Eric Wilen (PI), Chunlin Xu (PI), Hongbo Zhang (PI) & Ronald Österbacka (PI)Faculty of Science and Engineering
- 2 Aktiivinen
FCFH: Finland-China Network in Food and Health Sciences
Rosenholm, J., Xu, C. & Zhang, H.
Opetus- ja kulttuuriministeriö
01/01/21 → 31/12/24
Projekti: Ministry / Government Agency
Targeted delivery of CRISPR/Cas9 for advanced liver cancer therapy through c-Myc knockout
01/09/19 → 31/08/24
Projekti: Academy of Finland/Other Research Councils