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Updated: Apr 1, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Hybrid Collagenase Nanocapsules for Enhanced Nanocarrier Penetration in Tumoral Tissues
María Rocío Villegas1,2, Alejandro Baeza1,2, María Vallet-Regí1,2
1Departamento Química Inorgánica y Bioinorgánica, UCM, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12 , Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
Abstract:
Poor penetration of drug delivery nanocarriers within dense extracellular matrices constitutes one of the main liabilities of current nanomedicines. The conjugation of proteolytic enzymes on the nanoparticle surface constitutes an attractive alternative. However, the scarce resistance of these enzymes against the action of proteases or other aggressive agents present in the bloodstream strongly limits their application. Herein, a novel nanodevice able to transport proteolytic enzymes coated with an engineered pH-responsive polymeric is presented. This degradable coat protects the housed enzymes against proteolytic attack at the same time that it triggers their release under mild acidic conditions, usually present in many tumoral tissues. These enzyme nanocapsules have been attached on the surface of mesoporous silica nanoparticles, as nanocarrier model, showing a significatively higher penetration of the nanoparticles within 3D collagen matrices which housed human osteosarcoma cells (HOS). This strategy can improve the therapeutic efficacy of the current nanomedicines, allowing a more homogeneous and deeper distribution of the therapeutic nanosystems in cancerous tissues.
Insights
This study presents a novel nanodevice that protects proteolytic enzymes with a pH-responsive coat, enhancing drug delivery nanocarrier penetration into dense tumor tissues for improved cancer therapy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Drug Delivery
Background:
- Nanomedicine faces challenges with poor drug delivery nanocarrier penetration in dense extracellular matrices.
- Enzyme conjugation to nanoparticles offers potential but is limited by enzyme instability in the bloodstream.
Purpose of the Study:
- To develop a novel nanodevice for enhanced drug delivery nanocarrier penetration through dense tissues.
- To protect enzymes from degradation and enable targeted release in tumor microenvironments.
Main Methods:
- Engineered pH-responsive polymeric nanocapsules housing proteolytic enzymes were developed.
- These enzyme nanocapsules were coated onto mesoporous silica nanoparticles.
- Nanoparticle penetration was evaluated in 3D collagen matrices with human osteosarcoma cells (HOS).
Main Results:
- The pH-responsive coat protected enzymes from proteolytic degradation.
- Enzyme release was triggered under mild acidic conditions characteristic of tumoral tissues.
- Significant enhancement in nanoparticle penetration within 3D collagen matrices was observed.
Conclusions:
- This enzyme nanocapsule strategy improves nanoparticle distribution in cancerous tissues.
- The approach offers a promising method to overcome penetration barriers in nanomedicine.
- Enhanced tissue penetration can improve the therapeutic efficacy of nanomedicines.
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