Abstract
Mesoporous silica nanoparticles have been broadly applied as drug delivery systems owing to their exquisite features, such as excellent textural properties or biocompatibility. However, there are various biological barriers that prevent their proper translation into the clinic, including: (1) lack of selectivity toward tumor tissues, (2) lack of selectivity for tumoral cells and (3) endosomal sequestration of the particles upon internalization. In addition, their open porous structure may lead to premature drug release, consequently affecting healthy tissues and decreasing the efficacy of the treatment. First, this review will provide a comprehensive and systematic overview of the different approximations that have been implemented into mesoporous silica nanoparticles to overcome each of such biological barriers. Afterward, the potential premature and non-specific drug release from these mesoporous nanocarriers will be addressed by introducing the concept of stimuli-responsive gatekeepers, which endow the particles with on-demand and localized drug delivery.
Highlights
In the last few decades, the application of nanotechnology to medicine, the so-called nanomedicine, has attracted much interest among the scientific community, and it is expected to revolutionize the biotechnological and healthcare industries in the near future [1,2,3]
Aside from serving as targeting agents for the CD44 receptor, hyaluronic acid (HA) [156,158,352] and chondroitin sulfate [160,162] can be employed as gatekeepers for enzyme-responsive mesoporous silica nanoparticles (MSNs), as they are both degraded by hyaluronidase, an enzyme that can be found in the lysosomes
The great features that mesoporous silica nanoparticles offer have boosted their application for cancer treatment
Summary
In the last few decades, the application of nanotechnology to medicine, the so-called nanomedicine, has attracted much interest among the scientific community, and it is expected to revolutionize the biotechnological and healthcare industries in the near future [1,2,3]. Drug-loaded MSNs should be able to release their cargo only inside the tumoral cells To obtain such behavior, researchers have focused on the development of stimuli-responsive gatekeepers. Schematic representation of relevant barriers that mesoporous silica nanoparticles (MSNs) have to face wwhen aaddministered to aa ppaattiieenntt These barriers include potential premature release and difffferent bbiioological barriers, such as llaack ooff aaccccuummulation in ttuummor ttiissssues, lack ooff aaccccuumulation in ccaanncceerr cceellllss aanndd sseeqquueessttrraattiioonn iinn tthhee eennddoo--llyyssoossoommeess. That non-universality of the EPR effect has fueled the development of active approaches to improve the delivery of nanoparticles to the tumor tissues Examples of this strategy include the use of tumor-tropic peptides and tumor-tropic cells, among others
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