Related Experiment Video
Updated: Aug 7, 2025
Monitoring of Nanodrug Accumulation in Murine Breast Cancer Metastases
Published on: August 23, 2024
Nanocarrier of Pin1 inhibitor based on supercritical fluid technology inhibits cancer metastasis by blocking multiple
Fengzhu Zhang1, Aiwen Zhang1, Youning Xie1
1Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, 350108, PR China.
Abstract:
Cancer metastasis is the primary cause of all cancer-related deaths due to the lack of effective targeted drugs that simultaneously block multiple signaling pathways that drive the dissemination and growth of cancer cells. The unique proline isomerase Pin1 activates numerous cancer pathways, but its role in cancer metastasis and the inhibitory efficacy of Pin1 inhibitors on cancer metastasis are unknown. Moreover, the applicability of Pin1 inhibitor-all-trans retinoic acid (ATRA) is limited due to its several drawbacks. Herein, uniform ATRA-loaded polylactic acid-polyethylene glycol block copolymer nanoparticles (ATRA-NPs) with high encapsulation efficiency, good cellular uptake, excellent controlled release performance and pharmacokinetics are developed using supercritical carbon dioxide processing combined with an optimized design. ATRA-NPs exhibited excellent biosafety and significant inhibition on the growth and metastasis of hepatocellular carcinoma. Pin1 played a key role in cancer metastasis and was the main target of ATRA-NPs. ATRA-NPs exerted their potent anti-metastatic effect by inhibiting Pin1 and then simultaneously blocking multiple signaling pathways and cancer epithelial-mesenchymal progression. Since ATRA-NPs could effectively couple the inhibition of cancer cell dissemination with cancer growth, it provided a novel therapeutic strategy for efficiently inhibiting cancer metastasis.
Insights
Novel nanoparticles deliver all-trans retinoic acid (ATRA) to inhibit cancer metastasis by targeting Pin1, blocking multiple pathways, and improving drug delivery for hepatocellular carcinoma treatment.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Cancer metastasis is a leading cause of cancer mortality, driven by complex signaling pathways.
- The proline isomerase Pin1 activates cancer pathways, but its role in metastasis and inhibition efficacy are unclear.
- All-trans retinoic acid (ATRA) has limitations as a Pin1 inhibitor.
Purpose of the Study:
- To develop effective ATRA-loaded nanoparticles (ATRA-NPs) for cancer metastasis inhibition.
- To investigate the role of Pin1 in cancer metastasis and its targeting by ATRA-NPs.
- To evaluate the therapeutic potential of ATRA-NPs against hepatocellular carcinoma.
Main Methods:
- Supercritical carbon dioxide processing was used to create uniform ATRA-loaded polylactic acid-polyethylene glycol block copolymer nanoparticles (ATRA-NPs).
- The study assessed nanoparticle characteristics, including encapsulation efficiency, cellular uptake, controlled release, and pharmacokinetics.
- In vitro and in vivo models were used to evaluate the biosafety and anti-metastatic efficacy of ATRA-NPs on hepatocellular carcinoma.
Main Results:
- ATRA-NPs demonstrated high encapsulation efficiency, good cellular uptake, controlled release, and favorable pharmacokinetics.
- The developed nanoparticles exhibited excellent biosafety and significantly inhibited hepatocellular carcinoma growth and metastasis.
- Pin1 was identified as a key mediator of cancer metastasis and the primary target of ATRA-NPs.
Conclusions:
- ATRA-NPs effectively inhibit cancer metastasis by targeting Pin1, simultaneously blocking multiple signaling pathways and epithelial-mesenchymal transition.
- This novel nanoparticle-based strategy couples the inhibition of cancer cell dissemination and growth.
- ATRA-NPs offer a promising therapeutic approach for efficiently combating cancer metastasis.
