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Title: Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices

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 (SLBs). 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 ofmore » the transported drug as a consequence of its more homogeneous distribution throughout the tumoral tissue.« less
Authors:
 [1] ; ORCiD logo [1] ;  [2] ;  [2] ;  [3] ;  [2] ; ORCiD logo [4] ;  [1]
  1. Univ. Complutense Madrid (Spain); Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid (Spain)
  2. Univ. of New Mexico, Albuquerque, NM (United States)
  3. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States)
  4. Univ. of New Mexico, Albuquerque, NM (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Publication Date:
Report Number(s):
SAND2018-9208J
Journal ID: ISSN 0897-4756; 667256
Grant/Contract Number:
AC04-94AL85000
Type:
Accepted Manuscript
Journal Name:
Chemistry of Materials
Additional Journal Information:
Journal Volume: 30; Journal Issue: 1; Journal ID: ISSN 0897-4756
Publisher:
American Chemical Society (ACS)
Research Org:
Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Sponsoring Org:
USDOE National Nuclear Security Administration (NNSA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES
OSTI Identifier:
1469638

Villegas, María Rocío, Baeza, Alejandro, Noureddine, Achraf, Durfee, Paul N., Butler, Kimberly S., Agola, Jacob Ongudi, Brinker, C. Jeffrey, and Vallet-Regí, María. Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices. United States: N. p., Web. doi:10.1021/acs.chemmater.7b03128.
Villegas, María Rocío, Baeza, Alejandro, Noureddine, Achraf, Durfee, Paul N., Butler, Kimberly S., Agola, Jacob Ongudi, Brinker, C. Jeffrey, & Vallet-Regí, María. Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices. United States. doi:10.1021/acs.chemmater.7b03128.
Villegas, María Rocío, Baeza, Alejandro, Noureddine, Achraf, Durfee, Paul N., Butler, Kimberly S., Agola, Jacob Ongudi, Brinker, C. Jeffrey, and Vallet-Regí, María. 2017. "Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices". United States. doi:10.1021/acs.chemmater.7b03128. https://www.osti.gov/servlets/purl/1469638.
@article{osti_1469638,
title = {Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices},
author = {Villegas, María Rocío and Baeza, Alejandro and Noureddine, Achraf and Durfee, Paul N. and Butler, Kimberly S. and Agola, Jacob Ongudi and Brinker, C. Jeffrey and Vallet-Regí, María},
abstractNote = {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 (SLBs). 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.},
doi = {10.1021/acs.chemmater.7b03128},
journal = {Chemistry of Materials},
number = 1,
volume = 30,
place = {United States},
year = {2017},
month = {12}
}