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Updated: Jan 17, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
Selective and spatiotemporal‑resolved nano-PROTAC for lung cancer therapy
Xiaowei Xu1, Le Wang2, Shitao Lin1
1The first Affiliated Hospital, The fifth Affiliated Hospital, Guangzhou Municipal and Guangdong Provincial KeyLaboratory of Molecular Target & Clinical Pharmacology, the NMPA and StateKey Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 511436, PR China.
Abstract:
The Proteolysis-Targeting Chimeras (PROTAC) technology has become a promising tool in lung cancer therapy. The PROTAC regents targeting to Bromodomain-containing Protein 4 (BRD4) showed effective induction of apoptosis in lung cancer cells. However, the application of this kind of PROTAC regents is still hindered by the low tissue specificity, solubility, and detectability. Herein, we developed a selective and spatiotemporal‑resolved nano-PROTAC, which was constructed using the functional polymer Poly(lactic-co-glycolic acid)-Polyethylene glycol 2000-Maleimide (PLGA-PEG-Mal) to load PROTAC regent dBET6 and the fluorescence dye, and further modification with aptamer targeting to the lung cancer cells. The drug-loaded nanoparticles can be uptaken by lung cancer cells effectively, inducing the complete degradation of BRD4 and effective apoptosis of lung cancer cells. In vivo experiments indicated that the aptamer-modified nanoparticles accumulated in the tumors, which led to the effective suppression of tumor growth in the tumor-bearing mouse model. Furthermore, this type of nano-PROTAC was endowed with real-time tracking capability, avoiding the extra and tedious modifications. The integrated diagnosis and treatment system showed great promise in lung cancer therapy.
Insights
This study introduces a novel nano-PROTAC system for lung cancer therapy, enhancing specificity and enabling real-time tracking. The aptamer-modified nanoparticles effectively degrade BRD4, induce apoptosis, and suppress tumor growth in mice.
Area of Science:
- Biomedical Engineering
- Oncology
- Nanotechnology
Background:
- Proteolysis-Targeting Chimeras (PROTAC) show promise for lung cancer therapy by targeting Bromodomain-containing Protein 4 (BRD4).
- Current PROTAC applications face limitations in tissue specificity, solubility, and detectability.
Purpose of the Study:
- To develop a selective and spatiotemporal-resolved nano-PROTAC for improved lung cancer treatment.
- To enhance drug delivery, targeting, and real-time monitoring of PROTAC agents.
Main Methods:
- Constructed a nano-PROTAC using Poly(lactic-co-glycolic acid)-Polyethylene glycol 2000-Maleimide (PLGA-PEG-Mal) to encapsulate the PROTAC reagent dBET6 and a fluorescence dye.
- Modified nanoparticles with an aptamer for targeted delivery to lung cancer cells.
- Evaluated in vitro efficacy (BRD4 degradation, apoptosis) and in vivo performance (tumor accumulation, growth suppression, real-time tracking) in a mouse model.
Main Results:
- Nano-PROTAC effectively induced BRD4 degradation and apoptosis in lung cancer cells.
- Aptamer-modified nanoparticles showed enhanced accumulation in tumors and suppressed tumor growth in vivo.
- The system provided real-time tracking capabilities without additional modifications.
Conclusions:
- The developed nano-PROTAC offers a selective and spatiotemporal-resolved approach for lung cancer therapy.
- This integrated diagnostic and therapeutic system demonstrates significant potential for advancing lung cancer treatment.
