Local hypoxia is a common feature of many solid tumors and may lead to unsatisfactory chemotherapy outcomes. Anaerobic bacteria that have an affinity to hypoxic areas can be used to achieve targeted drug delivery in tumor tissues. In this study, we developed a biocompatible bacteria/nanoparticles biohybrid (Bif@DOX-NPs) platform that employs the anaerobic Bifidobacterium infantis (Bif) to deliver adriamycin-loaded bovine serum albumin nanoparticles (DOX-NPs) into breast tumors. The Bif@DOX-NPs retained the targeting ability of B. infantis to hypoxic regions, as well as the cytotoxicity of DOX. The biohybrids were able to actively colonize the hypoxic tumors and significantly increased drug accumulation at the tumor site. The DOX concentration in the tumor masses colonized by Bif@DOX-NPs was 4 times higher than that in the free DOX-treated tumors, which significantly prolonged the median survival of the tumor-bearing mice to 69 days and reduced the toxic side-effects of DOX. Thus, anaerobic bacteria-based biohybrids are a highly promising tool for the targeted treatment of solid tumors with inaccessible hypoxic regions. 

/pdf/bacteria-driven-hypoxia-targeting-delivery-of-3igfc6qm.pdf

Bacteria-driven hypoxia targeting delivery of chemotherapeutic drug proving outcome of breast cancer

Chemotherapy still plays a dominant role in cancer treatment. However, the inability of conventional chemotherapeutic drugs to reach the hypoxic zone of solid tumors significantly weakens their efficacy. Bacteria-mediated drug delivery systems can be an effective targeting strategy for improving the therapeutic outcomes in cancer. Anaerobic bacteria have the unique ability to selectively transport drug loads to the hypoxic regions of tumors.We designed a Bifidobacterium infantis (Bif)-based biohybrid (Bif@PDA-PTX-NPs) to deliver polydopamine (PDA)-coated paclitaxel nanoparticles (PTX-NPs) to tumor tissues.The self-driven Bif@PDA-PTX-NPs maintained the toxicity of PTX as well as the hypoxic homing tendency of Bif. Furthermore, Bif@PDA-PTX-NPs significantly inhibited the growth of A549 xenografts in nude mice, and prolonged the survival of the tumor-bearing mice compared to the other PTX formulations without any systemic or localized toxicity.The Bif@PDA-PTX-NPs biohybrids provide a new therapeutic strategy for targeted chemotherapy to solid tumors. 

/pdf/bacteria-driven-tumor-microenvironment-sensitive-3puhc7ak.pdf

Bacteria-Driven Tumor Microenvironment-Sensitive Nanoparticles Targeting Hypoxic Regions Enhances the Chemotherapy Outcome of Lung Cancer

Abstract High intensity focused ultrasound (HIFU) has demonstrated its safety, efficacy and noninvasiveness in the ablation of solid tumor. However, its further application is limited by its inherent deficiencies, such as postoperative recurrence caused by incomplete ablation and excessive intensity affecting surrounding healthy tissues. Recent research has indicated that the integration of nanomaterials with HIFU exhibits a promising synergistic effect in tumor ablation. The concurrent utilization of nanomaterials with HIFU can help overcome the limitations of HIFU by improving targeting and ablation efficiency, expanding operation area, increasing operation accuracy, enhancing stability and bio-safety during the process. It also provides a platform for multi-therapy and multi-mode imaging guidance. The present review comprehensively expounds upon the synergistic mechanism between nanomaterials and HIFU, summarizes the research progress of nanomaterials as cavitation nuclei and drug carriers in combination with HIFU for tumor ablation. Furthermore, this review highlights the potential for further exploration in the development of novel nanomaterials that enhance the synergistic effect with HIFU on tumor ablation.

Application of high intensity focused ultrasound combined with nanomaterials in anti-tumor therapy

High-intensity focused ultrasound (HIFU) is a promising and representative non-invasive therapeutic method for treating cancer with a high degree of efficacy. This non-invasive method induces tumour cell necrosis by increasing the local temperature and mechanical pressure. However, the clinical application of HIFU is limited given its low penetration depth and the incidence of off-target side effects. With their promising structural adjustability and targeting ability, nanomedicines have been adopted to improve the ablative efficacy of HIFU in the treatment of cancer. By selectively changing the acoustic environment (tissue structure, density and blood supply) of tumour tissue, these nanomedicines may allow for lower HIFU doses and treatment duration, while additionally achieving a higher degree of efficacy. The use of nanomedicines may also enable cancer theranostics of HIFU, allowing for precise cancer therapeutics. The present review aimed to provide an overview of advances in nanomedicines for HIFU cancer treatment and theranostics, stating their current limitations and future perspectives.

/pdf/nanomedicines-for-high-intensity-focused-ultrasound-cancer-2cdumlaz.pdf

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

In recent years, the in-depth study of low-frequency sonophoresis (LFS) has greatly elucidated its biological effects in various therapeutic applications, including drug delivery, enhanced healing, thrombolytic technology, anti-inflammatory effects and tumor treatment. Specifically, numerous studies have reported its use in drug delivery and synergistic antitumor activity, indicating a new treatment direction for cancer. However, there are significant gaps in the understanding of LFS in terms of frequency and sound intensity safety; these issues are becoming increasingly important in understanding the biological effects of LFS ultrasound. This article reviews the treatment mechanism and current applications of LFS technology and discusses and summarizes its safety and application prospects.

Advances in Biological Application of and Research on Low-Frequency Ultrasound.

Objective Anaerobic bacteria can enter the solid tumor in the hypoxic region to colonize and proliferate. Aggregation of nanoparticles in the tumor area can enhance molecular imaging and therapy. It is hypothesized that the combination of the two could possibly achieve better imaging and tumor treatment. This study presents a biocompatible bacteria-based system that can deliver cationic phase-change nanoparticles (CPNs) into solid tumor to achieve enhanced imaging and treatment integration. Materials and methods Cationic phase-change nanoparticles (CPNs) and Bifidobacterium longum (BF) were mixed to determine the best binding rate and were placed in an agar phantom for ultrasonography. BF-CPNs complex adhesion to breast cancer cells was observed by laser confocal microscopy. In vivo, BF-CPNs and control groups were injected into tumors in breast cancer nude mouse models. Nanoparticles distribution was observed by ultrasound and in vivo fluorescence imaging. HIFU ablation was performed after injection. Gross and histological changes were compared and synergy was evaluated. Results Bifidobacterium longum (BF) and CPNs were combined by electrostatic adsorption. The BF-CPNs particles could increase the deposition of energy after liquid-gas phase-change during High Intensity Focused Ultrasound (HIFU) irradiation of tumor. Conclusions This study shows a valid method in diagnosis and therapy integration for providing stronger imaging, longer retention time, and more effective tumor treatment.

Experimental study on synergistic effect of HIFU treatment of tumors using Bifidobacterium bound with cationic phase-change nanoparticles.

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Experimental study on synergistic effect of HIFU treatment of tumors using Bifidobacterium bound with cationic phase-change nanoparticles.