Nanoparticles for multimodal antivascular therapeutics: Dual drug release, photothermal and photodynamic therapy

Abstract

The poor delivery of nanoparticles to target cancer cells hinders their success in the clinical setting. In this work, an alternative target readily available for circulating nanoparticles has been selected to eliminate the need for nanoparticle penetration in the tissue: the tumor blood vessels. A tumor endothelium-targeted nanoparticle (employing an RGD-containing peptide) capable of co-delivering two anti-vascular drugs (one anti-angiogenic drug and one vascular disruption agent) is here presented. Furthermore, the nanodevice presents two additional anti-vascular capabilities upon activation by Near-Infrared light: provoking local hyperthermia (by gold nanorods in the system) and generating toxic reactive oxygen species (by the presence of a photosensitizer). RGD-targeting is shown to increase uptake by HUVEC cells, and while the nanoparticles are shown not to be toxic for these cells, upon Near-Infrared irradiation their almost complete killing is achieved. The combination of all four therapeutic modalities is then evaluated in an ex ovo fibrosarcoma xenograft model, which shows a significant reduction in the number of blood vessels irrigating the xenografts when the nanoparticles are present, as well as the destruction of the existing blood vessels 2 upon irradiation. These results suggest that the combination of different anti-vascular therapeutic strategies in a single nanocarrier appears promising and should be further explored in the future.

Mesoporous Silica Nanoparticles for the Treatment of Complex Bone Diseases: Bone Cancer, Bone Infection and Osteoporosis

“…As it happens with many other cancer cells, bone tumoral cells overexpress specific receptors that can be targeted using conveniently engineered MSNs. Aside from targeting MSNs to osteosarcoma [137], the RGD motif can also be employed to recognize endothelial cells, which can help MSNs target the tumor endothelium of fibrosarcoma to then eliminate the cancerous cells using multimodal therapy [138]. In this sense, folic acid can be employed to target overexpressed folate receptors in fibrosarcoma [139] and osteosarcoma cells [126].…”

Gold nanoparticle‑mediated delivery of paclitaxel and nucleic acids for cancer therapy (Review)

“…Targeted AuNPs. in addition to simple aunPs that are used for drug and nucleic acid delivery and PTT, multifunctional aunPs have been designed for targeted delivery mediated by pH, short peptides, aptamers, antibodies and receptors (52)(53)(54)(55)(56)(57). Glutathione (GSH)-coated au-Fe 3 o 4 nanoshells for doxorubicin (doX) delivery feature a GSH layer on the nanoshell surface that is attached with an au-S native bond, which is stable at physiological pH but rapidly broken down in acidic tumor microenvironments, resulting in local doX release and cytotoxicity (52).…”

“…Porous silicon nPs in a complex with gold nanorods have been designed for delivery of a three-drug combination of hydrophilic and hydrophobic drugs (afb, doX and rapamycin), and the inclusion of afb, which targets Her-2 and eGFr. This construct confers targeted drug delivery to malignant cells, while gold nanorods facilitate PTT (56). This candidate has demonstrated positive results in vitro and in vivo (56).…”

“…This construct confers targeted drug delivery to malignant cells, while gold nanorods facilitate PTT (56). This candidate has demonstrated positive results in vitro and in vivo (56).…”

“…The use of short peptides, antibodies and receptors in the design of targeted aunPs is receiving increasing attention. Paris et al (56) recently investigated a novel strategy of targeting tumor angiogenesis rather than disrupting malignant cells. a tumor vascular endothelium-targeting nanoparticle was designed by incorporating an isoaspGly-arg peptide that targets αβ-integrin-overexpressing cells (For example, tumor vascular endothelia), an anti-angiogenic drug (doX), a vascular disrupting agent (fosbretabulin) and a gold nanorod.…”