Inhibited Metastasis and Amplified Chemotherapeutic Effects by Epigene-Transfection Based on a Tumor-Targeting
Mengzhu Wang1, Zhigang Wang1, Bin Qiao1
1Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People's Republic of China.
Purpose:
Tumor metastasis and drug resistance have always been vital aspects to cancer mortality and prognosis. To compromise metastasis and drug resistance, a nanoparticle IPPD-PHF2 (IR780/PLGA-PEI(Dox)-PHF2) has been engineered to accomplish efficient targeted epigenotherapy forced by PHF2-induced MET (mesenchymal to epithelial transition).
Materials And Methods:
IPPD-PHF2 nanoparticle was synthesized and characterized by several analytical techniques. The transfection efficiency of IPP-PHF2 (IR780/PLGA-PEI-PHF2) was compared with PP-PHF2 (PLGA-PEI-PHF2) in vitro by WB and in vivo by IHC, and the cytotoxicity of IPP was compared with Lipo2000 in vitro by CCK8 assay. The inhibition of cancer cell migration caused by PHF2-upregulation was tested by wound healing assay, and the enhanced chemotherapeutic sensitivity was detected by flow cytometry. Tumor-targeting property of IPPD-PHF2 was proved by fluorescent imaging in vivo with MDA-MB-231 tumor-bearing nude mice. Except for fluorescent imaging ability, considerable photoacoustic signals of IPPD-PHF2 at tumor sites were verified. The anti-tumor activity of IPPD-PHF2 was investigated using in vivo human breast cancer MDA-MB-231 cell models.
Results:
Tumor-targeting nanoparticle IPPD-PHF2 had an average size of about 319.2 nm, a stable zeta potential at about 38 mV. The encapsulation efficiency of doxorubicin was around 39.28%, and the adsorption capacity of plasmids was about 64.804 μg/mg. Significant up-regulation of PHF2 induced MET and caused reduced migration as well as enhanced chemotherapeutic sensitivity. Either IPPD (IR780/PLGA-PEI(Dox)) or IPP-PHF2 (IR780/PLGA-PEI-PHF2) presented minor therapeutic effects, whereas IPPD-PHF2 specifically accumulated within tumors, showed extraordinary transfection efficiency specifically in tumor sites, acted as inhibitors of metastasis and proliferation, and presented good multimodality imaging potentials in vivo.
Conclusion:
IPPD-PHF2 NPs is a promising tool to bring epigenotherapy into a more practical era, and the potential application of harm-free multimodality imaging guidance is of great value.
Insights
A novel nanoparticle, IPPD-PHF2, effectively targets tumors and induces mesenchymal-to-epithelial transition (MET) to combat cancer metastasis and drug resistance. This epigenotherapy approach shows promise for improved cancer treatment and multimodal imaging guidance.
Area of Science:
- Nanotechnology in oncology
- Epigenetics and cancer therapy
- Multimodal cancer imaging
Background:
- Tumor metastasis and drug resistance significantly impact cancer patient outcomes.
- Targeted epigenotherapy offers a strategy to overcome these challenges.
- Mesenchymal-to-epithelial transition (MET) is a key process in reversing metastasis.
Purpose of the Study:
- To engineer a nanoparticle, IPPD-PHF2, for targeted epigenotherapy.
- To leverage PHF2-induced MET to inhibit metastasis and drug resistance.
- To evaluate the therapeutic and imaging capabilities of IPPD-PHF2 in vivo.
Main Methods:
- Synthesis and characterization of IPPD-PHF2 nanoparticles.
- In vitro and in vivo assessment of transfection efficiency and cytotoxicity.
- Evaluation of cancer cell migration inhibition and chemotherapeutic sensitivity.
- In vivo tumor targeting, imaging (fluorescence and photoacoustic), and anti-tumor activity studies in a human breast cancer model.
Main Results:
- IPPD-PHF2 nanoparticles demonstrated efficient tumor targeting and accumulation.
- PHF2 upregulation via IPPD-PHF2 induced MET, reducing cell migration.
- Enhanced chemotherapeutic sensitivity was observed.
- The nanoparticle exhibited significant anti-tumor activity and multimodal imaging potential.
Conclusions:
- IPPD-PHF2 nanoparticles represent a promising platform for targeted epigenotherapy.
- This approach effectively compromises cancer metastasis and drug resistance.
- The integrated multimodal imaging guidance offers significant value for clinical application.
More Related Videos
14:20Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
08:02Isolation of Primary Cancer-Associated Fibroblasts from a Syngeneic Murine Model of Breast Cancer for the Study of Targeted Nanoparticles
Published on: May 14, 2021
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:38Mitogens and the Cell Cycle