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A Novel Bionic Catalyst-Mediated Drug Delivery System for Enhanced Sonodynamic Therapy.

ABSTRACT: Ultrasound (US)-triggered sonodynamic therapy (SDT) proves itself to be a formidable tool in the fight against cancer, due to its large spectrum of uses as a non-invasive therapeutic measure, while also demonstrating itself to be a certain improvement upon traditional SDT therapeutics. However, tumor hypoxia remains to be a major challenge for oxygen-dependent SDT. This study describes the development of an innovative, multi-use, catalyst-based and improved SDT targeting cancer, through the employment of a sonosensitizing curcumin (Cur) load embedded within a MnO₂ core, together with an extraneous tumor cell membrane component. The latter allows for efficient tumor recognition properties. Hollowed-out MnO₂ allows for efficient drug delivery, together with catalyzing oxygen generation from hydrogen peroxide present in tumor tissue, leading to enhanced SDT efficacy through the induction of a reduced hypoxic state within the tumor. In addition, Cur acts as a cytotoxic agent in its own right. The results deriving from in vivo studies revealed that such a biomimetic approach for drug-delivery actually led to a reduced hypoxic state within tumor tissue and a raised tumor-inhibitory effect within mouse models. Such a therapeutic measure attained a synergic SDT-based tumor sensitization treatment option, together with the potential use of such catalysis-based therapeutic formulations in other medical conditions having hypoxic states.

SUBMITTER: Yang Y

PROVIDER: S-EPMC8361452 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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A Novel Bionic Catalyst-Mediated Drug Delivery System for Enhanced Sonodynamic Therapy.

Yang Yiling Y Hua Shaohua S Suo Weilong W Wang Wenbin W Wang Longhao L Chen Zhengguang Z Liu Kefeng K Zhao Jie J

Frontiers in bioengineering and biotechnology 20210730

Ultrasound (US)-triggered sonodynamic therapy (SDT) proves itself to be a formidable tool in the fight against cancer, due to its large spectrum of uses as a non-invasive therapeutic measure, while also demonstrating itself to be a certain improvement upon traditional SDT therapeutics. However, tumor hypoxia remains to be a major challenge for oxygen-dependent SDT. This study describes the development of an innovative, multi-use, catalyst-based and improved SDT targeting cancer, through the empl ...[more]

PMID: 34395406

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Project description:BackgroundSonodynamic therapy (SDT) has shown promise as a non-invasive cancer treatment due to its local effects and excellent tissue penetration. However, the limited accumulation of sonosensitizers at the tumor site hinders its therapeutic efficacy. Although nanosonosensitizers have improved local tumor accumulation through passive targeting via the enhanced permeability and retention effect (EPR), achieving sufficient accumulation and penetration into tumors remains challenging due to tumor heterogeneity and inaccurate targeting. Bacteria have become a promising biological carrier due to their unique characteristic of active targeting and deeper penetration into the tumor.MethodsIn this study, we developed nanosonosensitizers consisting of sonosensitizer, hematoporphyrin monomethyl ether (HMME), and perfluoro-n-pentane (PFP) loaded poly (lactic-co-glycolic) acid (PLGA) nanodroplets (HPNDs). These HPNDs were covalently conjugated onto the surface of Escherichia coli Nissle 1917 (EcN) using carbodiimine chemistry. EcN acted as an active targeting micromotor for efficient transportation of the nanosonosensitizers to the tumor site in triple-negative breast cancer (TNBC) treatment. Under ultrasound cavitation, the HPNDs were disrupted, releasing HMME and facilitating its uptakes by cancer cells. This process induced reactive oxygen species (ROS)-mediated cell apoptosis and immunogenic cell death (ICD) in vitro and in vivo.ResultsOur bacteria-driven nanosonosensitizer delivery system (HPNDs@EcN) achieved superior tumor localization of HMME in vivo compared to the group treated with only nanosonosensitizers. This enhanced local accumulation further improved the therapeutic effect of SDT induced-ICD therapeutic effect and inhibited tumor metastasis under ultrasound stimulation.ConclusionsOur research demonstrates the potential of this ultrasound-responsive bacteria-driven nanosonosensitizer delivery system for SDT in TNBC. The combination of targeted delivery using bacteria and nanosonosensitizer-based therapy holds promise for achieving improved treatment outcomes by enhancing local tumor accumulation and stimulating ICD.

Project description:Sonodynamic therapy (SDT) has aroused great interest for its potential in the treatment of glioblastoma (GBM). SDT relies on tumor-selective accumulation of a sonosensitizer that is activated by ultrasound irradiation (UI) to generate cytotoxic actions. The efficacy of GBM-SDT depends on sufficient sonosensitizer buildup in the tumor, which is, however, seriously hampered by the anatomical and biochemical barriers of the GBM. To overcome this difficulty, we herein propose a delivery strategy of 'platelets with ultrasound-triggered release property', which takes advantage of 1) the platelets' ability to carry cargo and release cargo upon activation, and 2) the ROS-generating property of SDT. To provide proof of concept for the strategy, we first stably loaded platelets with IOPD-Ce6, a nano-formed sonosensitizer consisting of iron oxide nanoparticles coated with polyglycerol and doxorubicin and loaded with chlorine e6. UI of the IOPD-Ce6-loaded platelets (IOPD-Ce6@Plt) elicited ROS generation in the IOPD-Ce6@Plt, which were immediately activated to release IOPD-Ce6 into GBM cells in co-culture which, when subjected to a second time of UI, exhibited pronounced ROS production, DNA injury, viability loss, and cell death in the GBM cells. In the in vivo experiments, mice bearing intracranial GBM grafts exhibited substantial tumor distribution of IOPD-Ce6 following intravenous injection of IOPD-Ce6@Plt and subsequent UI at the tumor site. The GBM grafts then exhibited pronounced cell injury and death after another round of UI of the tumors. Finally, the growth of intra-cranial GBM grafts was significantly slowed when an SDT protocol consisting of an intravenous IOPD-Ce6@Plt injection followed by multiple times of tumor UI had been applied twice to the mice. Our results are strong evidence for the idea that platelets are sound and amenable carriers to deliver sonosensitizers in the GBM in an ultrasound-triggered manner and thus to produce highly targeted and effective SDT of GBM.

Project description:Rationale: Sympathetic hyperactivation and neuroinflammation are the main triggers of malignant ventricular arrhythmias (VAs) after myocardial infarction (MI). Previous studies proved that photothermal therapy (PTT) and photodynamic therapy (PDT) could reduce MI-induced VAs by inhibiting neuroinflammation. However, the limited penetration depth and potential phototoxicity of phototherapy impose constraints on its further application. As a treatment strategy derived from phototherapy, sonodynamic therapy (SDT) offers exceptional advantages, including excellent penetration capability, temporal-spatial controllability, superior efficacy and minimal side effects. Therefore, it is worthwhile to investigate the effects of sonodynamic modulation on neuroinflammation and arrhythmia prevention. Methods: We designed a long-wavelength emissive sonosensitizer (named BBTD-TPA) based on donor-acceptor-donor scaffold. Subsequently, the compound was encapsulated in DSPE-PEG5000 to form BBTD-TPA nanoparticles (NPs). In vitro experiments were conducted to determine the optimal concentration of BBTD-TPA NPs-mediated SDT and to verify the effects and pathways on autophagy in BV2 cells. The distribution and metabolism of BBTD-TPA NPs in vivo were assessed by NIR-II fluorescence imaging. Finally, in vivo studies were performed to assess the effect of BBTD-TPA NPs-mediated SDT on post-MI sympathetic neuroinflammation and the occurrence of VAs. Results: In vitro studies demonstrated that BBTD-TPA NPs combined with LIFU could promote microglial autophagy via the ROS-AMPK-mTOR pathway. BBTD-TPA NPs were further microinjected into the paraventricular nucleus (PVN), real-time NIR-II fluorescence imaging showed that BBTD-TPA NPs could remain in the PVN for up to 12 h and be metabolized through the liver and kidney. Further in vivo results verified that BBTD-TPA NPs-mediated SDT could inhibit sympathetic nervous activity, and inflammatory responses, thus preventing MI-induced VAs. Conclusion: BBTD-TPA NPs-mediated SDT can promote microglial autophagy and inhibit sympathetic neuroinflammation, thus reducing MI-induced VAs. The current research may inspire a novel strategy for neuromodulation and arrhythmia prevention, providing broader prospects for clinical translation of nanomedical technology.

Dataset Information

A Novel Bionic Catalyst-Mediated Drug Delivery System for Enhanced Sonodynamic Therapy.

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A Novel Bionic Catalyst-Mediated Drug Delivery System for Enhanced Sonodynamic Therapy.

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