Magnetically modified-mitoxantrone mesoporous organosilica drugs: an emergent multimodal nanochemotherapy for breast cancer.

BACKGROUND: Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge. RESULTS: In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe3O4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs. CONCLUSIONS: A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe3O4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.

Kidney-Protector Lipidic Cilastatin Derivatives as Structure-Directing Agents for the Synthesis of Mesoporous Silica Nanoparticles for Drug Delivery.

Mesoporous silica nanomaterials have emerged as promising vehicles in controlled drug delivery systems due to their ability to selectively transport, protect, and release pharmaceuticals in a controlled and sustained manner. One drawback of these drug delivery systems is their preparation procedure that usually requires several steps including the removal of the structure-directing agent (surfactant) and the later loading of the drug into the porous structure. Herein, we describe the preparation of mesoporous silica nanoparticles, as drug delivery systems from structure-directing agents based on the kidney-protector drug cilastatin in a simple, fast, and one-step process. The concept of drug-structure-directing agent (DSDA) allows the use of lipidic derivatives of cilastatin to direct the successful formation of mesoporous silica nanoparticles (MSNs). The inherent pharmacological activity of the surfactant DSDA cilastatin-based template permits that the MSNs can be directly employed as drug delivery nanocarriers, without the need of extra steps. MSNs thus synthesized have shown good sphericity and remarkable textural properties. The size of the nanoparticles can be adjusted by simply selecting the stirring speed, time, and aging temperature during the synthesis procedure. Moreover, the release experiments performed on these materials afforded a slow and sustained drug release over several days, which illustrates the MSNs potential utility as drug delivery system for the cilastatin cargo kidney protector. While most nanotechnology strategies focused on combating the different illnesses this methodology emphasizes on reducing the kidney toxicity associated to cancer chemotherapy.

Protein Corona over Mesoporous Silica Nanoparticles: Influence of the Pore Diameter on Competitive Adsorption and Application to Prostate Cancer Diagnostics.

Diagnostic tests based on proteomics analysis can have significant advantages over more traditional biochemical tests. However, low molecular weight (MW) protein biomarkers are difficult to identify by standard mass spectrometric analysis, as they are usually present at low concentrations and are masked by more abundant resident proteins. We have previously shown that mesoporous silica nanoparticles are able to capture a predominantly low MW protein fraction from the serum, as compared to the protein corona (PC) adsorbed onto dense silica nanoparticles. In this study, we begin by further investigating this effect using liquid chromatography-mass spectrometry (LC-MS)/MS and thermogravimetric analysis (TGA) to compare the MW of the proteins in the coronas of mesoporous silica nanoparticles with the same particle size but different pore diameters. Next, we examine the process by which two proteins, one small and one large, adsorb onto these mesoporous silica nanoparticles to establish a theory of why the corona becomes enriched in low MW proteins. Finally, we use this information to develop a novel system for the diagnosis of prostate cancer. An elastic net statistical model was applied to LC-MS/MS protein coronas from the serum of 22 cancer patients, identifying proteins specific to each patient group. These studies help to explain why low MW proteins predominate in the coronas of mesoporous silica nanoparticles, and they illustrate the ability of this information to supplement more traditional diagnostic tests.