Related Experiment Video
Updated: Jul 18, 2025
Fabrication of Extracellular Matrix-derived Foams and Microcarriers as Tissue-specific Cell Culture and Delivery Platforms
Published on: April 11, 2017
Nanoformulations based on collagenases loaded into halloysite/Veegum® clay minerals for potential pharmaceutical
Marina Massaro1, Giulio Ghersi1, Raquel de Melo Barbosa2
1Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Parco d'Orleans II, Ed. 16-17, 90128 Palermo, Italy.
Abstract:
The design and development of nanomaterials capable of penetrate cancer cells is fundamental when anticancer therapy is involved. The use of collagenase (Col) is useful since this enzyme can degrade collagen, mainly present in the tumor extracellular matrix. However, its use is often limited since collagenase suffers from inactivation and short half-life. Use of recombinant ultrapure collagenase or carrier systems for their delivery are among the strategies adopted to increase the enzyme stability. Herein, based on the more stability showed by recombinant enzymes and the possibility to use them in anticancer therapy, we propose a novel strategy to further increase their stability by using halloysite nanotubes (HNTs) as carrier. ColG and ColH were supramolecularly loaded onto HNTs and used as fillers for Veegum gels. The systems could be used for potential local administration of collagenases for solid tumor treatment. All techniques adopted for characterization showed that halloysite interacts with collagenases in different ways depending with the Col considered. Furthermore, the hydrogels showed a very slow release of the collagenases within 24 h. Finally, biological assays were performed by studying the digestion of a type-I collagen matrix highlighting that once released the Col still possessed some activity. Thus we developed carrier systems that could further increase the high recombinant collagenases stability, preventing their inactivation in future in vivo applications for potential local tumor treatment.
Insights
We developed halloysite nanotube (HNT) carriers for collagenase (Col) enzymes, enhancing their stability for potential anticancer therapy. These HNT-based hydrogels offer slow enzyme release, maintaining collagenase activity for solid tumor treatment.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Enzyme Engineering
Background:
- Collagenase (Col) is crucial for degrading tumor extracellular matrix in anticancer therapy.
- Enzyme instability and short half-life limit collagenase efficacy.
- Recombinant enzymes and carrier systems are strategies to improve collagenase stability.
Purpose of the Study:
- To enhance the stability of recombinant collagenases (ColG and ColH) using halloysite nanotubes (HNTs) as a carrier system.
- To develop injectable hydrogel formulations for localized delivery of collagenase-loaded HNTs for solid tumor treatment.
- To evaluate the interaction, release kinetics, and enzymatic activity of collagenases from HNT-based hydrogels.
Main Methods:
- Supramolecular loading of ColG and ColH onto HNTs.
- Formulation of Veegum hydrogels incorporating HNT-collagenase complexes.
- Characterization of HNT-collagenase interactions using various techniques.
- In vitro assessment of collagenase release profiles from hydrogels over 24 hours.
- Biological assays to evaluate the collagenolytic activity of released enzymes on a type-I collagen matrix.
Main Results:
- Halloysite nanotubes demonstrated varied interactions with ColG and ColH.
- The developed hydrogels exhibited a sustained, slow release of collagenases over 24 hours.
- Released collagenases retained significant enzymatic activity against type-I collagen.
- The HNT carrier system effectively enhanced the stability of recombinant collagenases.
Conclusions:
- Halloysite nanotubes serve as effective carriers to increase the stability of recombinant collagenases.
- The developed HNT-based hydrogel systems facilitate localized delivery and sustained release of active collagenases.
- This strategy holds promise for improving the in vivo efficacy of collagenase-based anticancer therapies, particularly for solid tumors.
