On-Command Drug Release from Nanochains Inhibits Growth of Breast Tumors

Abstract

Purpose To evaluate the ability of radiofrequency (RF)-triggered drug release from a multicomponent chain-shaped nanoparticle to inhibit the growth of an aggressive breast tumor. Methods A two-step solid phase chemistry was employed to synthesize doxorubicin-loaded nanochains, which were composed of three iron oxide nanospheres and one doxorubicin-loaded liposome assembled in a 100-nm-long linear nanochain. The nanochains were tested in the Luc-GFP-4T1 orthotopic mouse model, which is a highly aggressive breast cancer model. The Luc-GFP-4T1 cell line stably expresses firefly luciferase, which allowed the non-invasive in vivo imaging of tumor response to the treatment using bioluminescence imaging (BLI). Results Longitudinal BLI imaging showed that a single nanochain treatment followed by application of RF resulted in an at least 100-fold lower BLI signal compared to the groups treated with nanochains (without RF) or free doxorubicin followed by RF. A statistically significant increase in survival time of the nanochain-treated animals followed by RF (64.3 days) was observed when compared to the nanochain-treated group without RF (35.7 days), free doxorubicin-treated group followed by RF (38.5 days), and the untreated group (30.5 days; n=5 animals per group). Conclusions These studies showed that the combination of RF and nanochains has the potential to effectively treat highly aggressive cancers and prolong survival.

Shaping Cancer Nanomedicine: The Effect of Particle Shape on The In Vivo Journey of Nanoparticles

“…Recently, it was shown that an 100-nm-long oblong chain-like nanoparticle (termed nanochain) composed of three iron oxide nanospheres and one doxorubicin-loaded liposome exhibited a 2-fold higher extravasation into tumors in a mammary adenocarcinoma model compared to spherical liposomal doxorubicin [93]. In addition, as a result of the multicomponent design of the nanochain, radiofrequency-triggered drug release from the particles resulted in the therapeutic efficacy being three-fold higher than treatments using spherical nanoparticles [93, 147]. Interestingly, the chain-shaped nanoparticle responded in a unique manner in the presence of a magnetic field.…”

Treatment of Invasive Brain Tumors Using a Chain-like Nanoparticle

“…The multicomponent nature and shape of the particle result in two unique features that facilitate effective treatment of difficult-to-treat brain tumors using a low dose of cytotoxic drugs as illustrated in Fig. 1C (7, 9, 10). Contrary to traditional small-molecule drugs or more contemporary nanotherapeutics, the nanochain particle possesses a unique ability to gain rapid access to and be deposited at brain tumor sites.…”

Vascular targeting of nanoparticles for molecular imaging of diseased endothelium

“…In addition, which leads to a new ‘interfering’ signal from EPR-driven deposition of the nanoparticle. To accurately differentiate vascular targeting from signals in the blood pool or deep-tissue, investigators have optimized and identified a low dose of nanoparticles agents that generated significantly detectable signal on the tumor-associated vascular bed and insignificant background “noise” due to the blood circulation of the nanoparticle or its non-specific uptake in various organs ( e.g ., liver, spleen) [85,88,87]. …”