Multifunctional Protocells for Enhanced Penetration in 3D Extracellular Tumoral Matrices
[1];
[4];
- Univ. Complutense Madrid (Spain); Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid (Spain)
- Univ. of New Mexico, Albuquerque, NM (United States)
- Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Univ. of New Mexico, Albuquerque, NM (United States)
- Univ. of New Mexico, Albuquerque, NM (United States); Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
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.
- Research Organization:
- Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
- Sponsoring Organization:
- USDOE National Nuclear Security Administration (NNSA)
- Grant/Contract Number:
- AC04-94AL85000
- OSTI ID:
- 1469638
- Report Number(s):
- SAND2018-9208J; 667256
- Journal Information:
- Chemistry of Materials, Vol. 30, Issue 1; ISSN 0897-4756
- Publisher:
- American Chemical Society (ACS)Copyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
Similar Records
Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry and Fluorescence Microscopy
Magnetic/NIR-responsive drug carrier, multicolor cell imaging, and enhanced photothermal therapy of gold capped magnetite-fluorescent carbon hybrid nanoparticles