In Vivo Evaluation of Multifunctional Gold Nanorods for Boron Neutron Capture and Photothermal Therapies

Abstract

The incidence and mortality of cancer demand more innovative approaches and combination therapies to increase treatment efficacy and decrease off-target side effects. We describe a boron-rich nanoparticle composite with potential applications in both boron neutron capture therapy (BNCT) and photothermal therapy (PTT). Our strategy is based on gold nanorods (AuNRs) stabilized with polyethylene glycol and functionalized with the water-soluble complex cobalt bis(dicarbollide) ([3,3′-Co­(1,2-C2B9H11)2]−), commonly known as COSAN. Radiolabeling with the positron emitter copper-64 (64Cu) enabled in vivo tracking using positron emission tomography imaging. 64Cu-labeled multifunctionalized AuNRs proved to be radiochemically stable and capable of being accumulated in the tumor after intravenous administration in a mouse xenograft model of gastrointestinal cancer. The resulting multifunctional AuNRs showed high biocompatibility and the capacity to induce local heating under external stimulation and trigger cell death in heterogeneous cancer spheroids as well as the capacity to decrease cell viability under neutron irradiation in cancer cells. These results position our nanoconjugates as suitable candidates for combined BNCT/PTT therapies.

Transforming Nuclear Medicine with Nanoradiopharmaceuticals

“…These 64 Cu-labeled multifunctionalized AuNRs were robustly taken up by gastrointestinal tumor xenografts in mice following systemic administration, without any noticeable side effect. PET-imaging mediated tumor detection followed by both light-activated photothermal therapy (PTT) and neutron-irradiated BNCT of the tumor could be achieved, thus demonstrating image-guided combination therapy using a single nanoplatform in vivo …”

“…PET-imaging mediated tumor detection followed by both light-activated photothermal therapy (PTT) and neutron-irradiated BNCT of the tumor could be achieved, thus demonstrating image-guided combination therapy using a single nanoplatform in vivo. 169 Gadolinium NCT nanoformulations have been reported with nanoparticles containing chelated gadolinium ions, entrapped gadolinium compounds, as well as gadolinium as an intrinsic part of the nanoparticles. Tokumitsu et al compared the NCT abilities of the commercial gadopentetate (complex of gadolinium and DTPA) solutions to that of gadopentetic acid−chitosan complex nanoparticles.…”

Photothermal and Photodynamic Therapy of Tumors with Plasmonic Nanoparticles: Challenges and Prospects

“…AuNRs were incorporated into mesoporous silica [97,98], biodegradable polymeric matrix [99], and liposomes to facilitate the targeted release of ruthenium(II) polypyridyl complexes [100]. For more detailed information, the readers are referred to resent original papers [101][102][103][104][105][106][107][108][109] and related citations in recent reviews [77,[110][111][112][113][114][115].…”

Polyglycerol Functionalized 10B Enriched Boron Carbide Nanoparticle as an Effective Bimodal Anticancer Nanosensitizer for Boron Neutron Capture and Photothermal Therapies

“…Although nanomaterials sensitizing both PTT and BNCT, or bimodal nanosensitizers, were synthesized to conjugate gold nanorods or gold NPs with boron cluster, only in vitro cell experiments were carried out in the presence of the nanosensitizer under irradiation of light and neutrons, not simultaneously nor consecutively (dual modality), but independently (single modality). [29,30] In contrast to the above conjugates of gold and boron moieties, boron carbide NPs possess two modalities in a single nanomaterial, because they were recently reported to work as a PTT nanosensitizer. [31,32] In this work, we designed and prepared a 10 B enriched boron carbide NP ( 10 B 4 C) functionalized with polyglycerol (PG), a hydrophilic polymer alternative to polyethylene glycol (PEG).…”