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

Abstract

In this study a mesoporous silica nanoparticle (MSNP) based platform is developed for high‐dose loading of a range of activated platinum (Pt) chemo agents that can be attached to the porous interior through the use of electrostatic and coordination chemistry under weak‐basic pH conditions. In addition to the design feature for improving drug delivery, the MSNP can also be encapsulated in a coated lipid bilayer (silicasome), to improve the colloidal stability after intravenous (IV) injection. Improved pharmacokinetics and intratumor delivery of encapsulated activated oxaliplatin (1,2‐diamminocyclohexane platinum(II) (DACHPt)) over free drug in an orthotopic Kras‐derived pancreatic cancer (PDAC) model is demonstrated. Not only does IV injection of the DACHPt silicasome provide more efficacious cytotoxic tumor cell killing, but can also demonstrate that chemotherapy‐induced cell death is accompanied by the features of immunogenic cell death (ICD) as well as a dramatic reduction in bone marrow toxicity. The added ICD features are reflected by calreticulin and high‐mobility group box 1 expression, along with increased CD8+/FoxP3+ T‐cell ratios and evidence of perforin and granzyme B release at the tumor site. Subsequent performance of a survival experiment, demonstrates that the DACHPt silicasome generates a significant improvement in survival outcome, which can be extended by delayed administration of the anti‐PD‐1 antibody.

Combined Fluorescence and Optoacoustic Imaging for Monitoring Treatments against CT26 Tumors with Photoactivatable Liposomes

“…More recently, silicasome (lipid bilayer mesoporous silica nanoparticle) has shown an improved IRI loading capacity and stability over the liposomal carrier model. Silicasome demonstrated improved pharmacokinetics, substantially improved efficacy, increased survival, and reduced bone marrow and GI toxicity compared to the free drug and Onivyde and tumor drug content over free drug and Onivyde, in orthotopic colon cancer model [ 86 , 87 ]. Employing an alternate approach, it has been shown by Chen et al [ 88 ] that embedding silica-coated nanobowls in the hydrophilic cavity, thus by providing mechanical support, can enhance drug leakage stability in blood circulation.…”

Modulating undruggable targets to overcome cancer therapy resistance

“…These MSNPs are then encapsulated in a coated lipid bilayer (silicasome) to improve its stability after i.v. injection (Liu et al, 2021). These NPs induce ICD but interestingly, are also associated with a dramatic reduction in bone marrow toxicity (Liu et al, 2021).…”

An Update on Mesoporous Silica Nanoparticle Applications in Nanomedicine

“…In another study, Liu et al used MSNs coated with lipid bilayers (silicasome) to deliver activated platinum chemo agent used for immunogenic chemotherapy in a pancreatic ductal adenocarcinoma (PDAC) preclinical model [ 387 , 388 ]. The silicasome coating improved the colloidal stability of this nanocarrier after the intravenous injection.…”