Photoacoustic Therapy for Precise Eradication of Glioblastoma with a Tumor Site Blood–Brain Barrier Permeability Upregulating Nanoparticle

Abstract

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.

Immunoengineering in glioblastoma imaging and therapy

“…In this study, an agonist for A2A adenosine receptor, a G protein‐coupled receptor expressed in endothelial cells of brain capillary, temporarily opened the BBB. Then, the PAMAM dendrimer modified with cyclic RGD peptides was efficiently delivered into the GBM, and the PA shockwave therapy selectively destroyed GBM tumors (L. Liu et al, ).…”

Liquid Metal Microparticles Phase Change Medicated Mechanical Destruction for Enhanced Tumor Cryoablation and Dual‐Mode Imaging

“…[7] So far, several researches have focused on the manipula tion of the mechanical properties of tumors in combination with chemotherapy or immunotherapy via adjusting the flow char acteristics inside the tumor microenviron ment, suppressing the stromal fibroblasts resistance, [8] alleviating hypoxia situation for drugs, molecules or nanomaterials etc. [9] Apart from the biomechanical regulation with molecules or nanodrugs, other mechanical destructions are also involved in the tumor therapies, mainly in use of photoacoustic shock wave, [10] highintensityfocused ultrasound (HIFU) [11] or even external magnetic field. [12] Materials that would produce nano sized or microsized bubbles under laser pulses or acoustic vibration are utilized, and these cavitation of bubbles would further induce a mechanical force to surrounding cells in local regions.…”

“…Apart from the biomechanical regulation with molecules or nanodrugs, other mechanical destructions are also involved in the tumor therapies, mainly in use of photoacoustic shockwave, [ 10 ] high‐intensity‐focused ultrasound (HIFU) [ 11 ] or even external magnetic field. [ 12 ] Materials that would produce nanosized or microsized bubbles under laser pulses or acoustic vibration are utilized, and these cavitation of bubbles would further induce a mechanical force to surrounding cells in local regions.…”

Single 808 nm near‐infrared‐triggered multifunctional upconverting phototheranostic nanocomposite for imaging‐guided high‐efficiency treatment of tumors

“…On the other hand, regarding the treatment efficacy, activatable agents with selective imaging guidance have been identified as an effective method [53][54][55][56][57]. In particular, photoacoustic (PA) imaging as a powerful optical imaging methodology could provide higher spatial resolution and deeper tissue penetration under NIR laser than other traditional optical imaging techniques [57][58][59][60][61]. And moreover, pulsed laser irradiation has also been demonstrated to generate significant ROS via photocavitations in aqueous conditions [62,63].…”