Large‐Pore Functionalized Mesoporous Silica Nanoparticles as Drug Delivery Vector for a Highly Cytotoxic Hybrid Platinum–Acridine Anticancer Agent

Abstract

Large-pore mesoporous silica nanoparticles (MSN) were prepared and functionalized to serve as a highly robust and biocompatible delivery platform for platinum-acridine (PA) anticancer agents. The material showed a high loading capacity for the dicationic, hydrophilic hybrid agent [PtCl(en)(N-[acridin-9-ylaminoethyl]-N-methylpropionamidine)] dinitrate salt (P1A1) and virtually complete retention of payload at neutral pH in a high-chloride buffer. In acidic media mimicking the pH inside the cell lysosomes, rapid, burst-like release of P1A1 from the nanoparticles is observed. Coating of the materials in phospholipid bilayers resulted in nanoparticles with greatly improved colloidal stability. The lipid and carboxylate-modified nanoparticles containing 40 wt % drug caused S-phase arrest and inhibited cell proliferation in pancreatic cancer cells at submicromolar concentrations similar to carrier-free P1A1. The most striking feature of nanoparticle-delivered P1A1 was that the payload did not escape from the acidified lysosomal vesicles into the cytoplasm, but was shuttled to the nuclear membrane and released into the nucleus.

Development of Facile and Versatile Platinum Drug Delivering Silicasome Nanocarriers for Efficient Pancreatic Cancer Chemo‐Immunotherapy

“…[ 14 ] The downside of a post‐grafting carboxyl modification, however, is that it interferes with LB coating, which is critical for colloidal stability and systemic biodistribution. [ 15 ] This likely explains why the studies were only carried out under tissue culture conditions rather than in vivo.…”

Preparation and Study of the Antibacterial Applications and Oxidative Stress Induction of Copper Maleamate-Functionalized Mesoporous Silica Nanoparticles

“…However, mesoporous silica-based materials have also been functionalized with metallodrugs of interest in cancer treatment, such as platinum compounds [7,8,9,10,11,12,13,14], titanium compounds [10,15,16,17,18,19,20,21,22,23], tin compounds [22,24,25] and even ruthenium photosensitizers [26], observing promising anticancer activity and a potential future application in clinical trials. The cellular action of these metallodrug-functionalized nanostructured silica-based materials showed that, in most cases, the nanosystems do not release the metallodrug to the biological medium (or the metallodrug release rates are very low), and they usually act as “non-classical” drug-delivery systems, whose cytotoxic activity is due to the action of the entire nanoparticle.…”

Mesoporous Silica Nanoparticle-Based Drug Delivery Systems for the Treatment of Pancreatic Cancer: A Systematic Literature Overview

“…Based on the favorable characteristics of liposomes, several papers describe the coating of MSNs with a lipid bilayer to improve stability after systemic administration, thereby overcoming one of the major limitations of MSNs in vivo. The majority of lipid membraneenhanced MSNs lack a targeted delivery moiety [58][59][60][61][63][64][65][66]68], however iRGD- [62] and cyclosporine A-conjugated [67] liposome-coated MSNs have been designed to improve tumor targeting and cellular uptake. Non-targeted irinotecan-loaded liposome-coated MSNs consistently outperform irinotecan-loaded liposomes, including FDA-approved Onivyde, in terms of drug delivery, cytotoxicity, survival as well by reducing bone marrow, gastrointestinal and liver toxicity [64,66].…”