Related Experiment Video
Updated: Oct 13, 2025
Manufacture and Drug Delivery Applications of Silk Nanoparticles
Published on: October 8, 2016
Enzyme-Induced Transformable Peptide Nanocarriers with Enhanced Drug Permeability and Retention to Improve Tumor
Zhongying Gong1, Baolong Zhou2, Xiaoying Liu1
1School of Bioscience and Technology, Weifang Medical University, Weifang 261053, China.
Abstract:
Temporal persistence is as important for nanocarriers as spatial accuracy. However, because of the insufficient aggreagtion and short retention time of chemotherapy drugs in tumors, their clinical application is greatly limited. A drug delivery approach dependent on the sensitivity to an enzyme present in the microenvironment of the tumor is designed to exhibit different sizes in different sites, achieving enhanced drug permeability and retention to improve tumor nanotherapy efficacy. In this work, we report a small-molecule peptide drug delivery system containing both tumor-targeting groups and enzyme response sites. This system enables the targeted delivery of peptide nanocarriers to tumor cells and a unique response to alkaline phosphatase (ALP) in the tumor microenvironment to activate morphological transformation and drug release. The amphiphilic peptide AYR self-aggregated into a spherical nanoparticle structure after encapsulating the lipid-soluble model drug doxorubicin (DOX) and rapidly converted to nanofibers via the induction of ALP. This morphological transformation toward a high aspect ratio allowed rapid, as well as effective drug release to tumor location while enhancing specific toxicity to tumor cells. Interestingly, this "transformer"-like drug delivery strategy can enhance local drug accumulation and effectively inhibit drug efflux. In vitro along with in vivo experiments further proved that the permeability and retention of antitumor drugs in tumor cells and tissues were significantly enhanced to reduce toxic side effects, and the therapeutic effect was remarkably improved compared with that of nondeformable drug-loaded peptide nanocarriers. The developed AYR nanoparticles with the ability to undergo morphological transformation in situ can improve local drug aggregation and retention time at the tumor site. Our findings provide a new and simple method for nanocarrier morphology transformation in novel cancer treatments.
Insights
This study introduces a peptide nanocarrier system that transforms in response to tumor enzymes, enhancing drug delivery and retention. This novel approach improves chemotherapy efficacy by increasing drug accumulation and reducing side effects.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery
Background:
- Chemotherapy drug delivery is limited by poor tumor aggregation and short retention times.
- Nanocarrier spatial accuracy is crucial, but temporal persistence is equally important for efficacy.
- Enzyme-responsive systems offer potential for targeted drug release in tumor microenvironments.
Purpose of the Study:
- To develop a peptide nanocarrier system that transforms in response to tumor-specific enzymes.
- To enhance drug permeability, retention, and efficacy in tumor nanotherapy.
- To investigate a novel drug delivery strategy for improved cancer treatment.
Main Methods:
- Designed a small-molecule peptide drug delivery system with tumor-targeting and enzyme-responsive elements.
- Utilized amphiphilic peptide AYR to encapsulate doxorubicin (DOX) into spherical nanoparticles.
- Induced morphological transformation from spheres to nanofibers using alkaline phosphatase (ALP) in the tumor microenvironment.
Main Results:
- AYR nanoparticles transformed into nanofibers upon ALP induction, facilitating rapid and effective drug release.
- Morphological transformation enhanced local drug accumulation and inhibited drug efflux.
- In vitro and in vivo studies demonstrated significantly improved drug permeability, retention, and reduced toxicity.
Conclusions:
- The developed AYR nanoparticles exhibit in situ morphological transformation, improving drug aggregation and retention at tumor sites.
- This enzyme-responsive, shape-shifting nanocarrier strategy offers a promising approach for enhanced cancer nanotherapy.
- The findings present a novel and simple method for nanocarrier morphology transformation in cancer treatment.
