Atherosclerotic plaques develop within the arterial intima, where rapid blood flow and high shear stress pose significant barriers to the adhesion of drug carriers to endothelial cells and their accumulation within plaques. To overcome these challenges, we developed a genetically engineered anaerobic bacterium, Shewanella oneidensis MR-1, harboring a plasmid encoding hirudin—a potent thrombin inhibitor—and green fluorescent protein (GFP). Notably, this system retains the intrinsic hypoxia-targeting capability of Shewanella oneidensis MR-1 and is designed to selectively release hirudin-loaded vesicles in response to the acidic microenvironment within plaques. These bioengineered vesicles enable site-specific drug release, promoting localized accumulation at the lesion. The released hirudin effectively dissolves thrombi embedded within vulnerable plaques and modulates foam cell metabolism, thereby attenuating plaque progression. Our results demonstrate that the SO@AHG system offers a novel and precise therapeutic strategy for atherosclerosis, and highlights the potential of bacteria-mediated targeted delivery for cardiovascular disease treatment.
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Research Article
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Lacking a precise targeting strategy, castration-resistant prostate cancer (CRPC) is still hard to be treat effectively. Exploring treatment options that can accurately target CPRC is an important issue with urgent need. In this study, a novel nanotechnology-based strategy had been developed for the precise target treatment of CRPC. By combining microwaves and photothermal therapy (PTT), this nanoplatform, cmHSP70-PL-AuNC-DOX, targets tumor tissues with outstanding precision and achieves better anti-tumor activity by simultaneously eliciting photothermal and chemotherapeutic effects. From nanotechnology, cmHSP70-modified and thermo-sensitive liposome-coated AuNC-DOX were prepared and used for CRPC-targeted photothermal ablation and chemotherapy. Doxorubicin (DOX) was selected as the chemotherapeutic agent for cytotoxicity. In terms of the curative scheme, prostate tissues were firstly pre-treated with microwaves to induce the expression of heat shock protein 70 (HSP70) and its migration to the cell membrane, which was then targeted by HSP70 antibody (cmHSP70) coated on the nanoparticles to achieve accurate drug delivery. The nanoplatform then achieved precise ablation and controlled release of DOX under external near-infrared (NIR) irradiation. Through the implementation, the targeting, cell killing, and safety of this therapeutical strategy had been verified in vivo and in vitro. This work establishes an accurate, controllable, efficient, non-invasive, and safe treatment platform for targeting CRPC, provides a rational design for CRPC’s PTT, and offers new prospects for nanomedicines with great precision.
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