Engineering Multifunctional Gold Decorated Dendritic Mesoporous Silica/Tantalum Oxide Nanoparticles for Intraperitoneal Tumor‐Specific Delivery

Abstract

Nonspecific high‐energy radiation for treatment of metastatic ovarian cancer is limited by damage to healthy organs, which can be mitigated by the use of radiosensitizers and image‐guided radiotherapy. Gold (Au) and tantalum oxide (TaOx) nanoparticles (NPs), by virtue of their high atomic numbers, find utility in the design of bimetallic NP systems capable of high‐contrast computed tomography (CT) imaging as well as a potential radiosensitizing effect. These two radio‐dense metals are integrated into dendritic mesoporous silica NPs (dMSNs) with radial porous channels for high surface‐area loading of therapeutic agents. This approach results in stable, monodispersed dMSNs with a uniform distribution of Au on the surface and TaOx in the core that exhibits CT attenuation up to seven times greater than iodine or monometallic dMSNs without either TaOx or Au. Tumor targeting is assessed in a metastatic ovarian cancer mouse model. Ex vivo micro‐CT imaging of collected tumors shows that these NPs not only accumulate at tumor sites but also penetrate inside tumor tissues. This study demonstrates that after intraperitoneal administration, rationally designed bimetallic NPs can simultaneously serve as targeted contrast agents for imaging tumors and to enhance radiation therapy in metastatic ovarian cancer.

Emerging Nanoagents for Medical X-ray Imaging

“…Recently, Kashfi-Sadabad et al reported a class of dendritic mesoporous silica/tantalum oxide nanoparticles adorned with gold for the treatment of metastatic ovarian cancer. 74 It is worth noting that the porous structure of the as-synthesized TaO x nanoparticles enabled the effective loading of radio-dense elements as imaging-guided radiotherapeutic nanoagents, leading to strong X-ray contrast enhancement and specific tumor targeting. Apart from tantalum-based contrast nanoagents, there are few reports about W-based contrast agents, because of their organ toxicity and environmental pollution issues.…”

“…Various modifications on the surface of the nanoparticles were performed to improve the biological properties of TaO x . Recently, Kashfi-Sadabad et al reported a class of dendritic mesoporous silica/tantalum oxide nanoparticles adorned with gold for the treatment of metastatic ovarian cancer . It is worth noting that the porous structure of the as-synthesized TaO x nanoparticles enabled the effective loading of radio-dense elements as imaging-guided radiotherapeutic nanoagents, leading to strong X-ray contrast enhancement and specific tumor targeting.…”

Imaging Tumor Heterogeneity and the Variations in Nanoparticle Accumulation Using Perfluorooctyl Bromide Nanocapsule X‐Ray Computed Tomography Contrast

“…[32] The employment of PEG on the surface of these nanocapsules was due to its potential in prolonging circulation half-life, as well as to provide similar surface chemistry when compared with other nanomedicines of interest (e.g., Doxil and Doxoves; PEGylated liposomal doxorubicin), considering the importance of surface chemistry on mass transport mechanisms associated with nanoparticle deliverability to tumors. Evidently, the use of radio-opaque nanoparticles for X-ray CT imaging has been explored before, mainly focusing on metalbased nanostructures due to their high X-ray attenuation, [47][48][49][50][51] or nanostructures encapsulating small-molecule iodinated (SMI) contrasts (e.g., iohexol, iopamidol). [52,53] With the purpose of employing radio-opaque nanoparticles as imaging probes for nanoparticle deliverability assessments, the PFOB NC system developed by our group displays greater potential as it combines a variety of characteristic: 1) their relevant particle size distribution when compared with commercial nanomedicines of interest (within 100-300 nm distribution range); 2) similar surface chemistry due to PEGylation conferred by the PEG-b-PCL(Ch) copolymer; 3) PFOB load easily tunable to a maximum of 40% v/v, [32] enhancing X-ray attenuation; and 4) high nanoparticleto-signal correlation as PFOB is a structural component of NC and it is unlikely to leak out, as observed for SMI contrast-loaded nanoparticles.…”

The Development of Nanoparticles for the Detection and Imaging of Ovarian Cancers

“…Additionally, folate-receptor targeting nanoparticles in the form of self-assembling biopolymer (100 nm) and dendrimer (5 nm) nanoparticles have been recently developed for ovarian cancer applications; however, they have yet to be studied in orthotopic tumor models [ 169 , 170 ]. Similarly for CT, nanoparticles devised of tantalum, mesoporous silica and surface attached gold nanoparticles, 166 nm in size, have demonstrated excellent CT contrast in a peritoneal tumor after intraperitoneal injection [ 171 ]. The encapsulation of perfluorooctyl bromide (an existing CT contrast agent) in targeted polymers nanoparticles has also been shown to be a potential CT molecular imaging agent in ovarian xenograft subcutaneous models [ 172 ].…”