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NEW JOURNAL OF CHEMISTRY · 2018 ·Vol. 42 ·期 12 ·9472-9481 · IF 3.201

Redox/ultrasound dual stimuli-responsive nanogel for precisely controllable drug release

Nengwei Shen,Bin Lei,Yizhou Wang,Shouhong Xu,Honglai Liu

Ultrasound is expected to be utilized in stimuli-responsive drug delivery systems (DDS) since it is safe, non-invasive and easy to control. In this study, a novel nanogel system with a redox/ultrasound dual stimuli-response has been developed for precise control of drug release. First, a thermo-sensitive copolymer PEIm–PNIPAMn–PEIm self-assembled into micelles in aqueous solution above its LCST. Then, PEI gel shell was formed by using a disulfide-containing cross-linker and spherical nanogels were obtained. Perfluorohexane (PFH) was introduced into the nanogels to provide a cavitation effect under an ultrasound stimulus. Furthermore, the PEI gel shell was specifically disintegrated by glutathione (GSH). The effects of redox/ultrasound on the structure and drug release of the nanogels were investigated. The release rate was found to be accelerated by the above-mentioned factors and a complete release was realized almost instantly. The release mechanism of the nanogels was then investigated. The dual stimuli-responsive nanogels present a promising application prospect for precisely controllable drug delivery/release.

CAS / MDL: 9002-98-6
研究领域: 药学 · 纳米技术 · 药物递送系统
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RSC Advances · 2023 ·Vol. 13 ·期 28 ·19065-19078 · IF 3.9

Tumor-homing bacterium-adsorbed liposomes encapsulating perfluorohexane/doxorubicin enhance pulsed-focused ultrasound for tumor therapy

Xia Ou,Zhong Zhang,Li Lin,Yan Du,Yu Tang,Yaotai Wang,Jianzhong Zou

Objective: To make up for the insufficient ultrasound ablation of tumors, the energy output or synergist is increased but faces the big challenge of normal tissue damage. In this study, we report a tumor-homing bacterium, Bifidobacterium bifidum (B. bifidum), adsorbing liposomes that encapsulate perfluorohexane (PFH) and doxorubicin (DOX) to enhance the pulsed-focused ultrasound (PFUS) for tumor therapy, so as to improve the efficacy, safety and controllability of ultrasound treatment. Methods: The PFH and DOX co-loaded cationic liposomal nanoparticles (CL-PFH-DOX-NPs) were prepared for ultrasound (US) imaging, cell-killing, and B. bifidum adsorption for the reactive oxygen species (ROS) testing. The aggregation of B. bifidum and CL-PFH-DOX-NPs is called tumor-homing aggregation (B. bifidum@CL-PFH-DOX-NPs) in this study, and the synergistic effects of B. bifidum@CL-PFH-DOX-NPs were analyzed in vivo. Results: Comprehensive studies validated that CL-PFH-DOX-NPs can enhance US imaging and cell-killing and B. bifidum can promote ROS, and B. bifidum@CL-PFH-DOX-NPs achieve PFUS synergism in vivo. Importantly, active homing of B. bifidum facilitated the delivery and retention of CL-PFH-DOX-NPs in tumors, reducing dispersion in normal tissues, achieving the targeting ability of B. bifidum@CL-PFH-DOX-NPs. The best sonication time was chosen according to the distribution of CL-PFH-DOX-NPs in vivo to achieve efficient therapy. Especially, B. bifidum@CL-PFH-DOX-NPs amplified cavitation and the immune-boosting effects. Conclusion: Multifunctional B. bifidum@CL-PFH-DOX-NPs were successfully constructed with well targeting, which not only realized US imaging monitoring, strong cavitation and complementary killing during PFUS, but also achieved immunity enhancement after PFUS. The combination of PFUS, B. bifidum and CL-PFH-DOX-NPs provides a new idea for the potential application of ultrasound therapy in solid tumors.

CAS / MDL: 1229-29-4 355-42-0
研究领域: 肿瘤学 · 生物医学工程 · 药学 · 治疗超声
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International Journal of Nanomedicine · 2022 · IF 7.033

Multifunctional Theranostic Nanoparticles for Enhanced Tumor Targeted Imaging and Synergistic FUS/Chemotherapy on Murine 4T1 Breast Cancer Cell

Zhengyue Kang,Min Yang,Xiaoling Feng,Hongjian Liao,Zhifei Zhang,Yonghong Du

Purpose Triple negative breast cancer (TNBC) is challenging for effective remission due to its very aggressive, extremely metastatic and resistant to conventional chemotherapy. Herein, a multifunctional theranostic nanoparticle was fabricated to enhance tumor targeted imaging and promote focused ultrasound (FUS) ablation and chemotherapy and sonodynamic therapy (SDT). A multi-modal synergistic therapy can improve the therapeutic efficacy and prognosis of TNBC.Methods AS1411 aptamer modified PEG@PLGA nanoparticles encapsulated with perfluorohexane (PFH) and anti-cancer drug doxorubicin (DOX) were constructed (AS1411-DOX/PFH-PEG@PLGA) to enhance tumor targeted imaging to guide ablation and synergistic effect of FUS/chemotherapy. FUS was utilized to trigger the co-release of doxorubicin and simultaneously PFH phase transition and activate DOX for SDT effect. The physicochemical, phase-changeable imaging capability, biosafety of nanoparticles and multi-mode synergistic effects on growth of TNBC were thoroughly evaluated in vivo and in vitro.Results The synthesized AS1411-DOX/PFH-PEG@PLGA (A-DPPs) nanoparticles are uniformly round with an average diameter of 306.03 ± 5.35 nm and the zeta potential of −4.05 ± 0.13 mV, displaying high biosafety and FUS-responsive drug release in vitro and in vivo. AS1411 modified NPs specifically bind to 4T1 cells and elevate the ultrasound contrast agent (UCA) image contrast intensity via PFH phase-transition after FUS exposure. Moreover, the combined treatment of A-DPPs nanoparticles with FUS exhibited significantly higher apoptosis rate, stronger inhibitory effect on 4T1 cell invasion in vitro, induced more reactive oxygen species (ROS), and enhanced anti-tumor effect compared to a single therapy (p < 0.05). Additionally, the joint strategy resulted in more intense cavitation effect and larger ablated areas and reduced energy efficiency factor (EEF) both in vitro and in vivo.Conclusion The multifunctional AS1411-DOX/PFH-PEG@PLGA nanoparticles can perform as a marvelous synergistic agent for enhanced FUS/chemotherapy, promote real-time contrast enhanced US imaging and improve the therapeutic efficacy and prognosis of TNBC.

研究领域: 肿瘤学 · 纳米技术 · 医学影像 · 癌症治疗 · 生物医学工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2023 · IF 5.8

A erythrocyte-platelet hybrid membrane coated biomimetic nanosystem based on ginsenosides and PFH combined with ultrasound for targeted delivery in thrombus therapy

Ming-Yue Yang,Yi-Fan Tu,Ke-Ke Feng,Meng-Die Yin,Yi-Fan Fang,Jing-Qing Le,Bang-Yue Luo,Xia-Rong Tan,Jing-Wei Shao

Thrombus is one of the culprits for global health problems. However, most current antithrombotic drugs are limited by restricted targeting ability and a high risk of systemic bleeding. A hybrid cell membrane-coated biomimetic nanosystem (PM/ [email protected] @P/R) was constructed in this paper to fulfil the targeted delivery of ginsenoside (Rg1) and perfluorohexane (PFH). Poly lactic-co-glycolic acid (PLGA) is used as carriers to coat Rg1 and PFH. Thanks to the camouflage of erythrocyte membrane (RM) and platelet membrane (PM), the nanosystem in question possesses remarkable features including immune escape and self-targeting. Therefore, a compact nano-core with [email protected] /R was formed, with a hybrid membrane covering the surface of the core, forming a “core-shell” structure. With its “core-shell” structure, this nanoparticle fancifully combines the advantages of both PFH (the low-intensity focused ultrasound (LIFU)-responsive phase-change thrombolysis) and Rg1(the antioxidant , anti-inflammatory and anticoagulant abilities). Meanwhile, PM/ [email protected] @P/R nanoparticles exhibits superior in-vitro performance in terms of ROS scavenging, anticoagulant activity and immune escape compared with those without cell membranes ( [email protected] /R). Furthermore, in the animal experiment in which the tail vein thrombosis model was established by injecting k-carrageenan, the combined treatment of LIFU and PM/ [email protected] @P/R showed a satisfactory antithrombotic efficiency (88.20 %) and a relatively higher biological safety level. This strategy provides new insights into the development of more effective and safer targeted biomimetic nanomedicines for antithrombotic treatments, possessing potential application in synergistic therapy field.

CAS / MDL: 355-42-0
研究领域: 纳米技术 · 药学 · 生物医学工程 · 治疗学
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