Discoidal Porous Silicon Particles: Fabrication and Biodistribution in Breast Cancer Bearing Mice

Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave, Houston, TX 77030, USA.
Advanced Functional Materials (Impact Factor: 11.81). 10/2012; 22(20):4225-4235. DOI: 10.1002/adfm.201200869
Source: PubMed


Porous silicon (pSi) is emerging as a promising material in the development of nanovectors for the systemic delivery of therapeutic and imaging agents. The integration of photolithographic patterning, typical of the semiconductor industry, with electrochemical silicon etching provides a highly flexible strategy to fabricate monodisperse and precisely tailored nanovectors. Here, a microfabrication strategy for direct lithographic patterning of discoidal pSi particles is presented that enables precise and independent control over particle size, shape, and porous structure. Discoidal pSi nanovectors with diameters ranging from 500 to 2600 nm, heights from 200 to 700 nm, pore sizes from 5 to 150 nm, and porosities from 40 to 90% are demonstrated. The degradation in serum, interaction with immune and endothelial cells in vitro, and biodistribution in mice bearing breast tumors are assessed for two discoidal nanovectors with sizes of 600 nm × 400 nm and 1000 nm × 400 nm. It is shown that both particle types are degraded after 24 h of continuous gentle agitation in serum, do not stimulate cytokine release from macrophages or affect endothelial cell viability, and accumulate up to about 10% of the injected dose per gram tissue in orthotopic murine models of breast cancer. The accumulation of the discoidal pSi nanovectors into the breast tumor mass is found to be up to five times higher than for spherical silica beads with similar diameters.

Download full-text


Available from: Ciro Chiappini, Oct 04, 2015
42 Reads
  • Source
    • "3.3. Tumor targeting and biodistribution of a-VEGFR2 MSV The biodistribution of untargeted and a-VEGFR2 targeted MSV was followed in breast tumor bearing mice using whole body near infrared (NIR) fluorescent imaging, a technique that has shown excellent correlation to other quantitative techniques to assess MSV biodistribution such as inductively coupled plasma e atomic emission spectroscopy [25] [26] [39] [40] [48]. The invasive murine 4T1 cells were chose to establish the breast cancer model. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Nanovectors are a viable solution to the formulation of poorly soluble anticancer drugs. Their bioaccumulation in the tumor parenchyma is mainly achieved exploiting the enhanced permeability and retention (EPR) effect of the leaky neovasculature. In this paper we demonstrate that multistage nanovectors (MSV) exhibit rapid tumoritropic homing independent of EPR, relying on particle geometry and surface adhesion. By studying endothelial cells overexpressing vascular endothelial growth factor receptor-2 (VEGFR2), we developed MSV able to preferentially target VEGFR2 expressing tumor-associated vessels. Static and dynamic targeting revealed that MSV conjugated with anti-VEGFR2 antibodies displayed greater than a 4-fold increase in targeting efficiency towards VEGFR2 expressing cells while exhibiting minimal adherence to control cells. Additionally, VEGFR2 conjugation bestowed MSV with a significant increase in breast tumor targeting and in the delivery of a model payload while decreasing their accumulation in the liver. Surface functionalization with an anti-VEGFR2 antibody provided enhanced affinity towards the tumor vascular endothelium, which promoted enhanced adhesion and tumoritropic accumulation of a reporter molecule released by the MSV.
    Biomaterials 08/2014; 35(37). DOI:10.1016/j.biomaterials.2014.08.024 · 8.56 Impact Factor
  • Source
    • "Compared to conventional form of dosage, micro- and nanomaterial-based drug delivery systems have many advantages, such as reduced release rate, minimized harmful side effects and improved therapeutic efficiency [7,14,15]. However, the premature release of active species from the cargo-loaded micropillars can represent a drawback. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We report on the fabrication of polyelectrolyte multilayer-coated hollow silicon dioxide micropillars as pH-responsive drug delivery systems. Silicon dioxide micropillars are based on macroporous silicon formed by electrochemical etching. Due to their hollow core capable of being loaded with chemically active agents, silicon dioxide micropillars provide additional function such as drug delivery system. The polyelectrolyte multilayer was assembled by the layer-by-layer technique based on the alternative deposition of cationic and anionic polyelectrolytes. The polyelectrolyte pair poly(allylamine hydrochloride) and sodium poly(styrene sulfonate) exhibited pH-responsive properties for the loading and release of a positively charged drug doxorubicin. The drug release rate was observed to be higher at pH 5.2 compared to that at pH 7.4. Furthermore, we assessed the effect of the number of polyelectrolyte bilayers on the drug release loading and release rate. Thus, this hybrid composite could be potentially applicable as a pH-controlled system for localized drug release.
    Nanoscale Research Letters 08/2014; 9(1):411. DOI:10.1186/1556-276X-9-411 · 2.78 Impact Factor
  • Source
    • "[18], [19] The biodistribution and biodegradability of pSi microparticles is well documented. [20]–[22] Functionally, pSi microparticles are proven carriers for nanoparticles, nucleic acids, peptides, and chemotherapeutic agents [23], [24]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Porous silicon (pSi) microparticles, in diverse sizes and shapes, can be functionalized to present pathogen-associated molecular patterns that activate dendritic cells. Intraperitoneal injection of MPL-adsorbed pSi microparticles, in contrast to free MPL, resulted in the induction of local inflammation, reflected in the recruitment of neutrophils, eosinophils and proinflammatory monocytes, and the depletion of resident macrophages and mast cells at the injection site. Injection of microparticle-bound MPL resulted in enhanced secretion of the T helper 1 associated cytokines IFN-γ and TNF-α by peritoneal exudate and lymph node cells in response to secondary stimuli while decreasing the anti-inflammatory cytokine IL-10. MPL-pSi microparticles independently exhibited anti-tumor effects and enhanced tumor suppression by low dose doxorubicin nanoliposomes. Intravascular injection of the MPL-bound microparticles increased serum IL-1β levels, which was blocked by the IL-1 receptor antagonist Anakinra. The microparticles also potentiated tumor infiltration by dendritic cells, cytotoxic T lymphocytes, and F4/80+ macrophages, however, a specific reduction was observed in CD204+ macrophages.
    PLoS ONE 04/2014; 9(4):e94703. DOI:10.1371/journal.pone.0094703 · 3.23 Impact Factor
Show more