Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices.



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Villegas Díaz, María Rocío and Baeza García, Alejandro and Nouredinne, Achraf and Durfee, Paul N and Butler, Kimberly S and Agola, Jacob Ongudi and Brinker, C.Jeffrey and Vallet Regí, María (2018) Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices. Chemistry of Materials, 30 (1). ISSN ISSN: 0897-4756 (In Press)

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The high density of the extracellular matrix in solid tumors is an important obstacle to nanocarriers for reaching deep tumor regions and has severely limited the efficacy of administrated nanotherapeutics. The use of proteolytic enzymes prior to nanoparticle administration or directly attached to the nanocarrier surface has been proposed to enhance their penetration, but the low in vivo stability of these macromolecules compromises their efficacy and strongly limits their application. Herein, we have designed a multifunctional nanocarrier able to transport cytotoxic drugs to deep areas of solid tumors and once there, to be engulfed by tumoral cells causing their destruction. This system is based on mesoporous silica nanocarriers encapsulated within supported lipid bilayers (SLB). The SLB avoids premature release of the housed drug while providing high colloidal stability and an easy to functionalize surface. The tumor penetration property is provided by attachment of engineered polymeric nanocapsules that transport and controllably unveil and release the proteolytic enzymes that in turn digest the extracellular matrix, facilitating the nanocarrier diffusion through the matrix. Additionally, targeting properties were endowed by conjugating an antibody specific to the investigated tumoral cells to enhance binding, internalization, and drug delivery. This multifunctional design improves the therapeutic efficacy of the transported drug as a consequence of its more homogeneous distribution throughout the tumoral tissue.

Item Type:Article
Additional Information:

RESEARCHER ID V-7077-2017 (María Rocío Villegas Díaz)
ORCID 0000-0002-1297-2355 (María Rocío Villegas Díaz)
RESEARCHER ID K-8193-2014 (Alejandro Baeza)
ORCID 0000-0002-9042-8865 (Alejandro Baeza)
RESEARCHER ID M-3378-2014 (María Vallet Regí)
ORCID 0000-0002-6104-4889 (María Vallet Regí)

Uncontrolled Keywords:Mesoporous silica nanoparticles, Supported lipid bilayers, Protocells, Penetration, Targeting, 3D tumoral tissue model
Subjects:Sciences > Chemistry > Materials
Sciences > Chemistry > Chemistry, Inorganic
ID Code:45826
Deposited On:01 Feb 2018 14:59
Last Modified:16 Dec 2018 00:01

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