Hyaluronan degrading silica nanoparticles for skin cancer therapy

We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly techniq...

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Bibliographic Details
Published in:Nanoscale 2013-10, Vol.5 (20), p.9690-9698
Main Authors: Scodeller, P, Catalano, P N, Salguero, N, Duran, H, Wolosiuk, A, Soler-Illia, G J A A
Format: Article
Language:English
Subjects:
Adjuvants
Animals
Antineoplastic Agents - administration & dosage
Cancer
Carboplatin - administration & dosage
Degradation
Drug Carriers - chemistry
Enzymes
Enzymes, Immobilized - chemistry
Enzymes, Immobilized - metabolism
Female
Humans
Hyaluronic Acid - metabolism
Hyaluronoglucosaminidase - chemistry
Hyaluronoglucosaminidase - metabolism
Melanoma - drug therapy
Melanoma - pathology
Mice
Mice, Nude
Nanoparticles
Nanoparticles - chemistry
Nanostructure
Porosity
Self assembly
Silicon Dioxide - chemistry
Skin Neoplasms - drug therapy
Skin Neoplasms - pathology
Transplantation, Heterologous
Tumors
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Summary:We report the first nanoformulation of Hyaluronidase (Hyal) and its enhanced adjuvant effect over the free enzyme. Hyaluronic acid (HA) degrading enzyme Hyal was immobilized on 250 nm silica nanoparticles (SiNP) maintaining specific activity of the enzyme via the layer-by-layer self-assembly technique. This process was characterized by dynamic light scattering (DLS), zeta potential, infrared and UV-Vis spectroscopy, transmission electron microscopy (TEM) and enzymatic activity measurements. The nanoparticles were tested in vivo as adjuvants of carboplatin (CP), peritumorally injected in A375 human melanoma bearing mice and compared with the non-immobilized enzyme, on the basis of equal enzymatic activity. Alcian Blue staining of A375 tumors indicated large overexpression of hyaluronan. At the end of the experiment, tumor volume reduction with SiNP-immobilized Hyal was significantly enhanced compared to non-immobilized Hyal. Field emission scanning electron microscopy (FE-SEM) images together with energy dispersive X-ray spectroscopy (EDS) spectra confirmed the presence of SiNP on the tumor. We mean a proof of concept: this extracellular matrix (ECM) degrading enzyme, immobilized on SiNP, is a more effective local adjuvant of cancer drugs than the non-immobilized enzyme. This could prove useful in future therapies using other or a combination of ECM degrading enzymes.
ISSN:2040-3364
2040-3372
DOI:10.1039/c3nr02787b