Related Experiment Video
Updated: Oct 14, 2025
Uptake of New Lipid-coated Nanoparticles Containing Falcarindiol by Human Mesenchymal Stem Cells
Published on: February 9, 2019
Triglyceride-Mimetic Structure-Gated Prodrug Nanoparticles for Smart Cancer Therapy
Chutong Tian1, Jingjing Guo1, Yifan Miao1
1Department of Pharmaceutics, Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, PR China.
Abstract:
Off-target drug release and insufficient drug delivery are the main obstacles for effective anticancer chemotherapy. Prodrug-based self-assembled nanoparticles bioactivated under tumor-specific conditions are one of the effective strategies to achieve on-demand drug release and effective tumor accumulation. Herein, stimuli-activable prodrugs are designed yielding smart tumor delivery by combination of the triglyceride-mimic (TG-mimetic) prodrug structure and disulfide bond. Surprisingly, these prodrugs can self-assemble into uniform nanoparticles (NPs) with a high drug loading (over 40%) and accumulate in tumor sites specifically. The super hydrophobic TG structure can act as a gate that senses lipase to selectively control over NP dissociation and affect the glutathione-triggered prodrug activation. In addition, the impacts of the double bonds in the prodrug NPs on parent drug release and the following cytotoxicity, pharmacokinetics, and antitumor efficiency are further demonstrated. Our findings highlight the promising potential of TG-mimetic structure-gated prodrug nanoparticles for tumor-specific drug delivery.
Insights
Novel triglyceride-mimic prodrug nanoparticles offer targeted cancer chemotherapy. These smart nanoparticles self-assemble, accumulate in tumors, and release drugs on demand, improving treatment efficacy.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Anticancer chemotherapy faces challenges with off-target drug release and insufficient delivery.
- Prodrug-based self-assembled nanoparticles activated by tumor-specific conditions offer a promising strategy for controlled drug release and tumor accumulation.
Purpose of the Study:
- To design stimuli-activable prodrugs for smart tumor delivery using a triglyceride-mimic (TG-mimetic) structure and disulfide bonds.
- To investigate the self-assembly, tumor-specific accumulation, and drug release mechanisms of these novel prodrug nanoparticles.
Main Methods:
- Synthesis of TG-mimetic prodrugs incorporating disulfide bonds.
- Characterization of self-assembled nanoparticles (NPs), including drug loading and size uniformity.
- In vitro and in vivo studies to evaluate lipase-triggered NP dissociation, glutathione-induced prodrug activation, drug release kinetics, cytotoxicity, pharmacokinetics, and antitumor efficiency.
Main Results:
- Prodrugs self-assembled into uniform nanoparticles with high drug loading (>40%).
- Nanoparticles exhibited specific accumulation in tumor sites.
- The TG-mimetic structure acted as a lipase-sensitive gate, controlling NP dissociation and influencing glutathione-triggered prodrug activation.
- Demonstrated the impact of double bonds on drug release, cytotoxicity, pharmacokinetics, and antitumor efficacy.
Conclusions:
- TG-mimetic structure-gated prodrug nanoparticles show significant potential for tumor-specific drug delivery in cancer chemotherapy.
- This approach offers on-demand drug release and enhanced tumor accumulation, overcoming key limitations of conventional chemotherapy.
