Related Experiment Video
Updated: Sep 13, 2025
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Precision targeting of ALK-positive lung cancer: Engineering HFN@MS4078 nanocages for optimized PROTAC delivery
Yuan Fan1, Yuxiang Liu2, Liujiao Wang2
1School of Environmental and Chemical Engineering, Shanghai University, 333 Nanchen Road, Shanghai 200444, PR China.
Abstract:
Protein hydrolysis-targeted chimeras (PROTACs) are heterobifunctional molecules designed for the selective degradation of target proteins. MS4078, a novel PROTAC, shows promise for treating ALK-positive non-small cell lung cancer (NSCLC), yet its clinical efficacy is hindered by suboptimal tumor targeting and off-target toxicities. To enhance its therapeutic profile, we developed human heavy chain ferritin (HFN) as a targeted delivery system, leading to the creation of HFN@MS4078 nanocages. Prepared via passive loading, HFN@MS4078 achieved a drug loading capacity of 178 molecules per nanocage with a HFN recovery rate of 70.1 %. The nanocages exhibited a rapid release profile under lysosomal conditions (pH 5.0), with approximately 80 % drug release after 60 h, while maintaining over 80 % stability at physiological pH 7.4. In vitro, HFN@MS4078 was actively internalized into lysosomes via TfR1 receptor binding, resulting in a 2.7-2.8 times reduction in IC50 values compared to free MS4078. Furthermore, HFN@MS4078 significantly decreased the expression levels of ALK, p-ALK, p-AKT, and p-ERK in NCI-H2228 and NCI-H3122 cell lines. In vivo, HFN@MS4078 substantially reduced tumor volume and prolonged survival while exhibiting negligible systemic toxicity. These results suggest that HFN@MS4078 represents a promising strategy for targeted therapy in ALK-positive NSCLC, enhancing therapeutic efficacy while minimizing systemic toxicity.
Insights
Human heavy chain ferritin (HFN) nanocages loaded with MS4078 PROTACs improve targeted delivery for ALK-positive non-small cell lung cancer (NSCLC). This HFN@MS4078 formulation enhances efficacy and reduces toxicity in preclinical models.
Area of Science:
- Biotechnology
- Nanomedicine
- Oncology
Background:
- Protein hydrolysis-targeted chimeras (PROTACs) offer selective protein degradation for cancer therapy.
- MS4078 is a PROTAC with potential against ALK-positive non-small cell lung cancer (NSCLC).
- Current limitations of MS4078 include suboptimal tumor targeting and off-target toxicities.
Purpose of the Study:
- To develop a targeted delivery system for MS4078 using human heavy chain ferritin (HFN).
- To evaluate the efficacy and safety of HFN-based MS4078 nanocages (HFN@MS4078) in ALK-positive NSCLC models.
Main Methods:
- HFN@MS4078 nanocages were prepared via passive loading.
- Drug loading capacity, release kinetics, and stability were characterized.
- In vitro cellular uptake, cytotoxicity (IC50), and target protein degradation were assessed.
- In vivo anti-tumor efficacy and systemic toxicity were evaluated in relevant NSCLC models.
Main Results:
- HFN@MS4078 achieved high drug loading and demonstrated pH-dependent release.
- Nanocages showed enhanced cellular internalization via TfR1 and significantly reduced IC50 values.
- HFN@MS4078 effectively reduced ALK pathway signaling (ALK, p-ALK, p-AKT, p-ERK) in NSCLC cells.
- In vivo studies showed substantial tumor volume reduction, prolonged survival, and minimal systemic toxicity.
Conclusions:
- HFN@MS4078 nanocages represent a promising targeted delivery strategy for ALK-positive NSCLC.
- This formulation enhances therapeutic efficacy and significantly mitigates systemic toxicity.
- HFN-based nanocarriers show potential for improving PROTAC delivery in cancer therapy.
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
