Silencing of aberrantly expressed microRNAs (miRNAs or miRs) has emerged as one of the strategies for molecular targeted cancer therapeutics. In particular, miR-21 is an oncogenic miRNA overexpressed in many tumors, including ovarian cancer. To achieve efficient administration of anti-miR therapeutics, delivery systems are needed that can ensure local accumulation in the tumor environment, low systemic toxicity, and reduced adverse side effects. In order to develop an improved anti-miR therapeutic agent for the treatment of ovarian cancer, a nanoformulation is engineered that leverages biodegradable porous silicon nanoparticles (pSiNPs) encapsulating an anti-miR-21 locked nucleic acid payload and displaying a tumor-homing peptide for targeted distribution. Targeting efficacy, miR-21 silencing, and anticancer activity are optimized in vitro on a panel of ovarian cancer cell lines, and a formulation of anti-miR-21 in a pSiNP displaying the targeting peptide CGKRK is identified for in vivo evaluation. When this nanoparticulate agent is delivered to mice bearing tumor xenografts, a substantial inhibition of tumor growth is achieved through silencing of miR-21. This study presents the first successful application of tumor-targeted anti-miR porous silicon nanoparticles for the treatment of ovarian cancer in a mouse xenograft model.
Porous silicon has been utilized within a wide spectrum of industries, as well as being used in basic research for engineering and biomedical fields. Recently, surface modification methods have been constantly coming under the spotlight, mostly in regard to maximizing its purpose of use. Within this review, we will introduce porous silicon, the experimentation preparatory methods, the properties of the surface of porous silicon, and both more conventional as well as newly developed surface modification methods that have assisted in attempting to overcome the many drawbacks we see in the existing methods. The main aim of this review is to highlight and give useful insight into improving the properties of porous silicon, and create a focused description of the surface modification methods.
Porous silicon nanoparticles (pSiNPs) have been utilized within a wide spectrum of biological studies, as well as in chemistry, chemical biology, and biomedical fields. Recently, pSiNPs have been constantly coming under the spotlight, mostly in biomedical applications, due to their advantages, such as controlled-release drug delivery in vivo by hydrolysis-induced degradation, self-reporting property through long life-time photoluminescence, high loading efficiency of substrate into pore, and the homing to specific cells/organ/bacteria by surface functionalization. However, the systematic degradation rate analysis of surface-functionalized pSiNPs in different biological media has not been conducted yet. In this paper, we prepared four different surface-functionalized pSiNPs samples and analyzed the degradation rate in six different media (DI H2O (deionized water), PBS (phosphate-buffered saline), HS (human serum), DMEM (Dulbecco’s modified Eagle’s medium), LB (lysogeny broth), and BHI (brain heart infusion)). The obtained results will now contribute to understanding the correlation between surface functionalization in the pSiNPs and the degradation rate in different biological media. The characterized data with the author’s suggestions will provide useful insights in designing the new pSiNPs formulation for biomedical applications.
The lack of drugs that target both disease progression
and tissue
preservation makes it difficult to effectively manage rheumatoid arthritis
(RA). Here, we report a porous silicon-based nanomedicine that efficiently
delivers an antirheumatic drug to inflamed synovium while degrading
into bone-remodeling products. Methotrexate (MTX) is loaded into the
porous silicon nanoparticles using a calcium silicate based condenser
chemistry. The calcium silicate–porous silicon nanoparticle
constructs (pCaSiNPs) degrade and release the drug preferentially
in an inflammatory environment. The biodegradation products of the
pCaSiNP drug carrier are orthosilicic acid and calcium ions, which
exhibit immunomodulatory and antiresorptive effects. In a mouse model
of collagen-induced arthritis, systemically administered MTX-loaded
pCaSiNPs accumulate in the inflamed joints and ameliorate the progression
of RA at both early and established stages of the disease. The disease
state readouts show that the combination is more effective than the
monotherapies.
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