Glioblastoma is an extremely difficult clinical indication with very few therapeutic choices. In this study, a nanoparticle is constructed featuring high red absorbance and selective penetration of the blood-brain barrier (BBB) at the tumor site. This nanoparticle can provide timely activation of the adenosine receptor on the BBB to allow self-passage and accumulation in the tumor. The nanoparticle converts pulsed laser energy into a shockwave via photoacoustic (PA) cavitation to achieve localized mechanical damage and thus yields a precision antitumor effect. In addition to its therapeutic function, the nanoparticle-mediated PA process can also generate images that provide valuable information regarding tumor depth, size, and vascular morphology to inform treatment planning and monitoring. The results show that the nanoparticles can be efficiently delivered into the glioblastoma via intravenous infusion and this PA shockwave therapy can selectively destroy glioblastoma tumors with no observable side effects on normal tissue. MCF-7 cells stained with CFSE, compared to the minimal signal in the U87-MG cells (Figure 4C, second column and fourth column). After PA therapy, U87-MG cells with Den-RCG/CGS/ Cy5.5 were destructed ( Figure 4C, first column, marked with the arrows). While the adjacent MCF-7 cells morphology maintain intact. These results suggest that, with a proper dosimetry, PA therapy could be a precise method to treat glioblastoma with minimal damage to the adjacent tissue.
Multifunctional nanoparticle-mediated imaging and therapeutic techniques are promising modalities for accurate localization and targeted treatment of cancer in clinical settings. Thermoacoustic (TA) imaging is highly sensitive to detect the distribution of water, ions or specific nanoprobes and provides excellent resolution, good contrast and superior tissue penetrability. TA therapy is a potential non-invasive approach for the treatment of deep-seated tumors. In this study, human serum albumin (HSA)-functionalized superparamagnetic iron oxide nanoparticle (HSA-SPIO) is used as a multifunctional nanoprobe with clinical application potential for MRI, TA imaging and treatment of tumor. In addition to be a MRI contrast agent for tumor localization, HSA-SPIO can absorb pulsed microwave energy and transform it into shockwave via the thermoelastic effect. Thereby, the reconstructed TA image by detecting TA signal is expected to be a sensitive and accurate representation of the HSA-SPIO accumulation in tumor. More importantly, owing to the selective retention of HSA-SPIO in tumor tissues and strong TA shockwave at the cellular level, HSA-SPIO induced TA effect under microwave-pulse radiation can be used to highly-efficiently kill cancer cells and inhibit tumor growth. Furthermore, ultra-short pulsed microwave with high excitation efficiency and deep penetrability in biological tissues makes TA therapy a highly-efficient anti-tumor modality on the versatile platform. Overall, HSA-SPIO mediated MRI and TA imaging would offer more comprehensive diagnostic information and enable dynamic visualization of nanoagents in the tumorous tissue thereby tumor-targeted therapy.
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