Investigation of the Therapeutic Effect of Doxorubicin Combined With Focused Shockwave on Glioblastoma

Abstract

BackgroundGlioblastoma multiforme (GBM) is currently the most devastating brain tumor globally and produces a high mortality rate. GBM is also challenging to eradicate using surgery due to its invasive characteristics. Moreover, the blood-brain barrier (BBB) increases the difficulty of transporting most therapeutic drugs to tumor sites. The use of transcranial focused ultrasound (FUS) has recently been investigated for opening the BBB to facilitate drug delivery. A special form of FUS, the shockwave (SW), has also been shown to open BBB efficiently. SW has several advantages including no heating effect, less reactive oxygen species production, good transcranial ability, and no need to supply microbubbles.MethodsWe employed a commercial SW device, which is a common tool used for musculoskeletal disorders, to improve doxorubicin delivery across the BBB and evaluated its therapeutic efficacy on GBM rat models. SW emits relatively short but stronger mechanical pulses comparing with FUS.ResultsThe results demonstrated that doxorubicin combined with SW treatment substantially inhibited tumor growth and prolonged overall survival.ConclusionsThe present study shows the non-invasive transcranial SW may have potential for the treatment of GBM in future clinical setting.

Focal opening of the neuronal plasma membrane by shock-induced bubble collapse for drug delivery: a coarse-grained molecular dynamics simulation

“…For example, a low-energy shockwave pulse was used to improve drug delivery through the BBB, such as penicillin G, doxorubicin, and bevacizumab, and evaluate their therapeutic efficacy in vivo. [15][16][17] Moreover, a molecular understanding of the interaction between paclitaxel (PTX) and cell membranes was also provided by MD simulations, 17 which pointed out that a suitable nano-bubble size and shock impulse are all necessary for the delivery of PTX into the cell. The result is basically consistent with the experiment, 18 that is, the existence of bubbles (or ultrasound contrast agents) is essential for successful drug delivery.…”

“…In parallel, focused shock waves (FSW) have also been developed for facilitating drug delivery across the BBB. 14,15 Compared with ultrasound, FSW need a lower total energy to open the BBB (about 1/60 000 times), and also generate negligible tissue heating and ROS. 16 Theoretically, the application of FSW would not be limited by tissue heating or related adverse effects.…”

Synthesis of Amphiphilic Copolymers of N-Vinyl-2-pyrrolidone and Allyl Glycidyl Ether for Co-Delivery of Doxorubicin and Paclitaxel

“…Doxorubicin, a common broad-spectrum drugs, has shown high efficacy in the treatment of breast cancer [26], lung cancer [27], gastric cancer [28], sarcoma [29], lymphoma [30], neuroblastoma [31], glioblastoma [32] and other oncological diseases [33]. Doxorubicin both intercalates into DNA [34] and stimulates the formation of radicals that damage cell membranes [35], which determines its antitumor activity.…”

The Role of microRNAs in Multidrug Resistance of Glioblastoma

“…Tumor cells can evade apoptosis via downregulating pro-apoptotic proteins and upregulating anti-apoptotic proteins. The escape of apoptosis has been widely observed in MDR against a variety of chemotherapeutics, including paclitaxel, doxorubicin, mitoxantrone, etoposide, cisplatin, and camptothecin [32][33][34].…”