Feasibility between Bifidobacteria Targeting and Changes in the Acoustic Environment of tumor Tissue for Synergistic HIFU

Abstract

High intensity focused ultrasound (HIFU) has been recently shown as a rapidly developing new technique for non-invasive ablation of local tumors whose therapeutic efficiency can be significantly improved by changing the tissue acoustic environment (AET). Currently, the method of changing AET is mainly to introduce a medium with high acoustic impedance, but there are some disadvantages such as low retention of the introduced medium in the target area and a short residence time during the process. In our strategy, anaerobic bacterium Bifidobacterium longum (B. longum) which can colonize selectively in hypoxic regions of the animal body was successfully localized and shown to proliferate in the hypoxic zone of tumor tissue, overcoming the above disadvantages. This study aimed to explore the effects of Bifidobacteria on AET (including the structure and acoustic properties of tumor tissues) and HIFU ablation at different time. The results show that the injection of Bifidobacteria increased the collagen fibre number, elastic modulus and sound velocity and decreased neovascularization in tumor tissues. The number of collagen fibres and neovascularization decreased significantly over time. Under the same HIFU irradiation intensity, the B. longum injection increased the coagulative necrosis volume and decreased the energy efficiency factor (EEF). This study confirmed that Bifidobacteria can change the AET and increase the deposition of ultrasonic energy and thereby the efficiency of HIFU. In addition, the time that Bifidobacteria stay in the tumor area after injection is an important factor. This research provides a novel approach for synergistic biologically targeted HIFU therapy.

A network meta-analysis to evaluate the efficacy of traditional Chinese medicine on intestinal flora in patients with gastrointestinal cancer

“…It also induces cell death through autophagy ( Engevik et al, 2019 ). Bifidobacterium can increase anti-PD-L1 and inhibit tumor volume by inducing anti-inflammatory activity of macrophages and dendritic cells ( Xu et al, 2020 ). Probiotics such as Lactobacillus and Bifidobacterium inhibit the growth of colorectal cancer by suppressing inflammation and angiogenesis, and enhance the intestinal barrier function by secreting short-chain fatty acids (SCFAs) ( Koh et al, 2016 ).…”

Novel combination strategy of high intensity focused ultrasound (HIFU) and checkpoint blockade boosted by bioinspired and oxygen-supplied nanoprobe for multimodal imaging-guided cancer therapy

“…2 3 However, the US radiation energy decays exponentially with increasing tissue depths and blood perfusion rates, which leads to insufficient energy accumulation in focal region, thus compromising the therapeutic efficiency of HIFU. 4 Classical strategy to strengthen ablation efficacy of HIFU is to increase the acoustic power or prolong the operation duration, but these options may lead to adverse biological effects such as transient pain, skin or nerve injury. 5 6 Some investigations have confirmed that the introduction of synergistic agents (SAs) is an efficient and alternative route to enhance HIFU surgical efficacy.…”

Nanomedicines for high‑intensity focused ultrasound cancer treatment and theranostics (Review)

“…Thus, bacteria such as Bifidobacterium have been considered as potential markers that may aid in the identification of tumour masses and facilitate tumour targeting diagnosis and treatment ( 74-76 ). When using Bifidobacterium as the targeting agent for tumour tissue, it could be either directly cross-linked to the delivery platform acting as an arch on a ‘bacterial robot’ or allowed to colonize in the tumour mass first, then another Bifidobacterium targeting NP can be utilized to achieve indirect targeting of the tumour ( 77 ). Jiang et al ( 78 ) compared these targeting strategies and found that when combined with HIFU ablation, the indirect targeting method was more efficient than cross-linking bacteria with NP payloads.…”