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Microbiology Spectrum · 2021 ·Vol. 9 ·期 3 · IF 7.171

A Nanobody-Mediated Virus-Targeting Drug Delivery Platform for the Central Nervous System Viral Disease Therapy

Song Zhu,Fei Luo,Bin Zhu,Fei Ling,Er-Long Wang,Tian-Qiang Liu,Gao-Xue Wang

Viral diseases of the central nervous system (CNS) represent a major global health concern. Difficulties in treating these diseases are caused mainly by the biological tissues and barriers, which hinder the transport of drugs into the CNS. To counter this, a nanobody-mediated virus-targeting drug delivery platform (SWCNTs-P-A-Nb) is constructed for CNS viral disease therapy. Viral encephalopathy and retinopathy (VER), caused by nervous necrosis virus (NNV), is employed as a disease model. SWCNTs-P-A-Nb is successfully constructed by employing single-walled carbon nanotubes, amantadine, and NNV-specific nanobody (NNV-Nb) as the nanocarrier, anti-NNV drug, and targeting ligand, respectively. Results showed that SWCNTs-P-A-Nb has a good NNV-targeting ability in vitro and in vivo, improving the specific distribution of amantadine in NNV-infected sites under the guidance of NNV-Nb. SWCNTs-P-F-A-Nb can pass through the muscle and gill and be excreted by the kidney. SWCNTs-P-A-Nb can transport amantadine in a fast manner and prolong the action time, improving the anti-NNV activity of amantadine. Results so far have indicated that the nanobody-mediated NNV-targeting drug delivery platform is an effective method for VER therapy, providing new ideas and technologies for control of the CNS viral diseases.IMPORTANCE CNS viral diseases have resulted in many deadly epidemics throughout history and continue to pose one of the greatest threats to public health. Drug therapy remains challenging due to the complex structure and relative impermeability of the biological tissues and barriers. Therefore, development in the intelligent drug delivery platform is highly desired for CNS viral disease therapy. In the study, a nanobody-mediated virus-targeting drug delivery platform is constructed to explore the potential application of targeted therapy in CNS viral diseases. Our findings hold great promise for the application of targeted drug delivery in CNS viral disease therapy.

研究领域: 医学 · 生物技术 · 药理学
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MATERIALS & DESIGN · 2025 · IF 7.9

GSH-responsive targeted copper-based nanoparticle improve ovarian cancer treatment via induction of apoptosis-ferroptosis-cuproptosis

Li Ma,Sihong Guo,Xinlei Yang,Hongyu Gao,Jie Chen

The combination of apoptosis-ferroptosis-cuproptosis provides a beneficial method for enhancing the curative effect of ovarian cancer (OC). In this study, we design and synthesize a nano-drug delivery platform, HTC@DOX, which is achieved by the self-assembly of an amphipathic molecule HA-SS-TOS-DTPA, Cu 2+ , and doxorubicin (DOX). HTC@DOX bring the combination of chemotherapy (CT) from DOX and the chemodynamic therapy (CDT) from Cu 2+ . In vitro and in vivo experimental results show that HTC@DOX have excellent stability and glutathione responsiveness. This platform efficiently and purposely targets tumor sites, and destroy OC cells through the synergy of CT and CDT by induce apoptosis-ferroptosis-cuproptosis, thus enhancing the anti-cancer efficacy with a tumor reduction rate of 92.3 %. In addition, the results of electrocardiogram, ultrasound and histopathological staining demonstrate that HTC@DOX have superior biological safety and alleviate the cardiotoxicity caused by DOX alone. The results of bulk RNA sequencing and western blot show the alterations of apoptosis, ferroptosis, and cuproptosis related indicators, which further corroborates the anti-tumor efficacy of HTC@DOX. In brief, this study verifies the feasibility and effectiveness of the combination of CT and CDT in the treatment of OC by inducing apoptosis-ferroptosis-cuproptosis, offering an innovative approach for the treatment of cancer.

CAS / MDL: 25316-40-9 67-68-5
研究领域: 肿瘤学 · 药剂学 · 生物医学工程
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ACS Applied Materials & Interfaces · 2024 · IF 8.3

Multilayered Shape-Morphing Scaffolds with a Hierarchical Structure for Uterine Tissue Regeneration

Shangsi Chen,Shenglong Tan,Liwu Zheng,Min Wang

Owing to dysfunction of the uterus, millions of couples around the world suffer from infertility. Different from conventional treatments, tissue engineering provides a new and promising approach to deal with difficult problems such as human tissue or organ failure. Adopting scaffold-based tissue engineering, three-dimensional (3D) porous scaffolds in combination with stem cells and appropriate biomolecules may be constructed for uterine tissue regeneration. In this study, a hierarchical tissue engineering scaffold, which mimicked the uterine tissue structure and functions, was designed, and the biomimicking scaffolds were then successfully fabricated using solvent casting, layer-by-layer assembly, and 3D bioprinting techniques. For the multilayered, hierarchical structured scaffolds, poly(l-lactide-co-trimethylene carbonate) (PLLA-co-TMC, “PLATMC” in short) and poly(lactic acid-co-glycolic acid) (PLGA) blends were first used to fabricate the shape-morphing layer of the scaffolds, which was to mimic the function of myometrium in uterine tissue. The PLATMC/PLGA polymer blend scaffolds were highly stretchable. Subsequently, after etching of the PLATMC/PLGA surface and employing estradiol (E2), polydopamine (PDA), and hyaluronic acid (HA), PDA@E2/HA multilayer films were formed on PLATMC/PLGA scaffolds to build an intelligent delivery platform to enable controlled and sustained release of E2. The PDA@E2/HA multilayer films also improved the biological performance of the scaffold. Finally, a layer of bone marrow-derived mesenchymal stem cell (BMSC)-laden hydrogel [which was a blend of gelatin methacryloyl (GelMA) and gelatin (Gel)] was 3D printed on the PDA@E2/HA multilayer films of the scaffold, thereby completing the construction of the hierarchical scaffold. BMSCs in the GelMA/Gel hydrogel layer exhibited excellent cell viability and could spread and be released eventually upon biodegradation of the GelMA/Gel hydrogel. It was shown that the hierarchically structured scaffolds could evolve from the initial flat shape into the tubular structure completely in an aqueous environment at 37 °C, fulfilling the requirement for curved scaffolds for uterine tissue engineering. The biomimicking scaffolds with a hierarchical structure and curved shape, high stretchability, and controlled and sustained E2 release appear to be very promising for uterine tissue regeneration.

研究领域: 生物医学工程 · 组织工程 · 再生医学
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MATERIALS & DESIGN · 2024 · IF 7.6

A Chemotherapy-Photothermal synergistic system in bifunctional bone Scaffold: Tumor therapy and bone repair

Wu Di,Yan zuyun,Cijun Shuai,Yaping Wang,Youwen Deng,Wei Zhang,Li xin,Yan-Ying Xiao,Tan Wei

Bone defect repair and tumor recurrence are the main challenges in the postoperative treatment of bone tumors. The incorporation of zoledronate (ZOL) into scaffolds presents a promising approach, attributed to its osteogenic and anti-tumor properties. However, there are still some unfavorable factors that make it difficult to eradicate tumor cells at the surgical site, including drug rapid release, the insufficient anti-tumor efficacy of ZOL and the multidrug resistance of chemotherapy. Herein, a novel nano drug delivery platform mesoporous silicon-coated graphene oxide (GO/MSN) and ZOL loaded nanoparticle (GO/MSN-ZOL) were developed. Then PLLA/ GO/MSN-ZOL scaffold that integrates photothermal therapy (PTT) and chemotherapy was fabricated using poly (L-lactic acid) as raw materials by selective laser sintering (SLS) technology. The GO not only imparted scaffold with photothermal properties for localized tumor cell ablation but also significantly enhanced its anti-tumor efficacy through synergistic effects in combination with chemotherapy. The mesoporous structure and large specific surface area of MSN contribute to the sustained release of ZOL. Additionally, GO could promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), which in combine with ZOL’s osteoclast inhibition, enhances the bone repair capacity. This study offers a straightforward and promising strategy for treating tumor-related bone defects.

研究领域: 生物医学工程 · 肿瘤学 · 骨科
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Fe-based metal-organic frameworks modified with carboxymethyl cellulose for targeted pesticide delivery and reducing biotoxicity

Jianguo Feng,Yifei Tan,Li Sun,Qianwei Liang,Tianzhen Jiang,Zhen Li

Traditional pesticide formulations have issues such as poor targeting, low adhesion performance, and a tendency to leach into the environment, causing pollution. In this study, a pesticide delivery platform (PRO@FeMOFs@CMC) with a dual response was designed by encapsulating prochloraz technical (PRO) within Fe-based metal–organic frameworks (FeMOFs) and using carboxymethyl cellulose (CMC) as the gatekeeper. The results showed that PRO@FeMOFs@CMC exhibited a loading capacity of 28.86 % for PRO and efficient adhesion to wheat and rice leaves. This delivery platform showed a significant increase in the release of PRO under environments similar to that produced by a pathogen infection, involving cellulase and glutathione (GSH). Importantly, compared to prochloraz suspension concentrate (PRO@SC), PRO@FeMOFs@CMC exhibited higher fungicidal efficacy against Rhizoctonia cereali and Rhizoctonia solani and its acute toxicity to zebrafish and earthworms was reduced by 3.7 times and 8.6 times, respectively. Compared to PRO@SC, the cells treated with PRO@FeMOFs@CMC had higher cell viability and a significantly reduced apoptosis rate, demonstrating greater safety. Additionally, FeMOFs@CMC showed no evident toxicity to wheat and rice. In summary, PRO@FeMOFs@CMC is an efficient and safe pesticide controlled-release system for the sustainable management of wheat and rice diseases.

CAS / MDL: 9004-32-4 9012-54-8
研究领域: 农业科学 · 环境科学 · 植物保护
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JOURNAL OF NANOBIOTECHNOLOGY · 2023 ·Vol. 21 ·期 1 ·1-19 · IF 10.2

Mesoporous polydopamine delivering 8-gingerol for the target and synergistic treatment to the spinal cord injury

Yang Jinpei,Wang Meng,Zheng Shuai,Huang Ruodong,Wen Ganjun,Zhou Pan,Wang Wenbo,Zhou Shihao,Jiang Xinlin,Liu Shuangjiang,Li Zhizhong,Ma Dong,Jiao Genlong

In the treatment of spinal cord injury (SCI), the complex process of secondary injury is mainly responsible for preventing SCI repair or even exacerbating the injury. In this experiment, we constructed the 8-gingerol (8G)-loaded mesoporous polydopamine (M-PDA), M@8G, as the in vivo targeting nano-delivery platform, and investigated the therapeutic effects of M@8G in secondary SCI and its related mechanisms. The results indicated that M@8G could penetrate the blood-spinal cord barrier to enrich the spinal cord injury site. Mechanism research has shown that all of the M-PDA,8G and M@8G displayed the anti-lipid peroxidation effect, and then M@8G can inhibit the secondary SCI by suppressing the ferroptosis and inflammation. In vivo assays showed that M@8G significantly diminished the local injury area, reduced axonal and myelin loss, thus improving the neurological and motor recovery in rats. Based on the analysis of cerebrospinal fluid samples from patients, ferroptosis occurred locally in SCI and continued to progress in patients during the acute phase of SCI as well as the stage after their clinical surgery. This study showcases effective treatment of SCI through the aggregation and synergistic effect of M@8G in focal areas, providing a safe and promising strategy for the clinical treatment of SCI.

CAS / MDL: 64-17-5 67-68-5 67-56-1
研究领域: 神经科学 · 药理学 · 纳米医学 · 生物医学工程
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Scientific Reports · 2022 ·Vol. 12 ·期 1 ·1-11 · IF 4.996

Zoledronate combined metal-organic frameworks for bone-targeting and drugs deliveries

Pan Yixiao,Wang Jiahao,Jiang Zichao,Guo Qi,Zhang Zhen,Li Jingyi,Hu Yihe,Wang Long

Medicine treatments for bone-related diseases such as osteoporosis, bone metastasis, osteomyelitis, and osteolysis are often limited by insufficient drug concentration at the lesion sites owing to the low perfusion of bone tissue. A carrier that can deliver multiple bone destruction site-targeting drugs is required to address this limitation. Here, we reported a novel bone-targeting nano-drug delivery platform formed by the integration of zoledronate (ZOL) and zeolitic imidazolate framework-8 (ZIF-8) nanoparticles. The ZOL mixed zeolitic imidazolate framework (ZZF) nanoparticles were synthesized in water at room temperature (25 °C), where many biomacromolecules could maintain their activity. This allowed the ZZF nanoparticles to adapt the encapsulation ability and pH response release property from ZIF-8 and the excellent bone targeting performance of ZOL simultaneously. Considering the ease of preparation and biomacromolecule-friendly drug delivery of this nano platform, it may be useful in treating bone-related diseases.

研究领域: 药学 · 纳米技术 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2025 · IF 12.5

A host/guest assembled hyaluronic acid-based supramolecular hydrogel with NIR-steered degradation capacity for enhanced tumor therapy through programmable drug release

Zejun Xu,Li Liu,Junkun Duan,Bei Guo,Jiayi Liu,Dongyan Liu,Fei Qin,Ruizhi Guo,Yingxia Bao,Jiansong Wang,Chuanbin Wu,Yi Zhang

Recently, a variety of stimulus-responsive hydrogel platforms have been developed, specifically designed to respond to changes in physiological signals within the disease microenvironment. However, due to the restricted regulation of drug release behavior in vivo by such hydrogel systems, the precise control of drug release kinetics has not been achieved. Therefore, developing precise drug delivery platforms that enable programmable and “on-off” delivery remains a challenge in this field. This study involved a supramolecular hydrogel platform (HACF) constructed with β -cyclodextrin-modified hyaluronic acid (HA-CD) and ferropentaene-modified hyaluronic acid (HA-Fc) for precise drug delivery and chemo-photothermal therapy by leveraging host-guest interactions between CD and Fc. The phthalocyanine green (ICG) and doxorubicin (DOX) were incorporated into the hydrogel network as photosensitizer and anticancer model drugs. Results demonstrated that ICG facilitated controlled disintegration of the hydrogel and led to responsive release of DOX in vitro under near-infrared (NIR) light stimulation. Furthermore, in vivo findings confirmed that NIR-steered programmed drug release from the hydrogel effectively enhanced anti-tumor efficacy and prevented tumor recurrence. In conclusion, this innovative NIR-driven supramolecular hydrogel platform not only presented a novel approach for remote and precise drug release but also provides a new platform for locally intelligent treatment across various clinical conditions.

CAS / MDL: 25316-40-9 7585-39-9
研究领域: 生物材料 · 纳米医学 · 药学 · 生物医学工程 · 肿瘤学 · 高分子化学
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MOLECULAR PHARMACEUTICS · 2023 · IF 4.9

Natural Polysaccharide Delivery Platforms with Multiscale Structure Used for Cancer Chemoimmunotherapy

Haifeng Ni,Sunxiang Qian,Jie Lu,Jie Feng,Xiao-zhou Mou,Jing Zhang

Chemoimmunotherapy is an effective cancer treatment method. Drugs are always combined and used in treating cancer. However, the characteristic of drugs varies, making it challenging to control their release kinetics utilizing delivery devices with a single microstructure. In this study, we attempted to uniformly size drugs of varying molecular weights and confine them in a compartment where immune cells may be recruited and moved freely. Dextran microgels were created as modular drug libraries to address the cryogel burst release of small molecule drugs. Then, modular drug libraries and granulocyte-macrophage colony-stimulating factor (GM-CSF) were integrated into cryogels for a combined treatment. Herein, alginate was zwitterion modified to avoid the immune reaction generated by the material. Because of its macroporous structure, the cryogel could be injected into the body, eliminating invasive surgical procedures. Results demonstrated that multiscale delivery platforms could improve the synergistic effect of various medications on tumor treatment.

研究领域: 药学 · 生物医学工程 · 癌症治疗 · 材料科学 · 免疫学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2025 · IF 11.5

Optimizing interventional therapy: A homogeneous lipiodol formulation of Tirapazamine and Sorafenib responsive to post-embolization microenvironment

Xing Gao,Hongwei Cheng,Minglei Teng,Hongrui Zhang,Hu Chen,Songnan Qu,Gang Liu

Transcatheter arterial chemoembolization (TACE) is the principal treatment option for patients with unresectable hepatocellular carcinoma (HCC). However, the hypoxic microenvironment following TACE can promote angiogenesis and suppress tumor ferroptosis, resulting in an unfavorable prognosis. Tirapazamine (TPZ), a hypoxia-activated prodrug with specific cytotoxicity for hypoxic cells, making it a potential candidate for TACE. To develop an effective hypoxia-responsive drug delivery platform for TACE, we propose a novel lipiodol embolic formulation that integrates TPZ and sorafenib (SFB) by super-stable homogeneous intermixed formulation technology (SHIFT). This approach achieves the manufacture of embolic agents with stable drug dispersion characteristics, fulfilling the need for sustained drug release in TACE. The prolonged tumor penetration of TPZ exhibited embolization-responsive tumor killing, and its combination with SFB can suppress hypoxia-induced angiogenesis and trigger tumor ferroptosis, maintaining low oxygen levels, thereby boosting the therapeutic efficacy of TPZ. Conversely, TPZ can combat the resistance to SFB in hypoxic tumor cells. In summary, this study developed a novel embolization drug formulation based on embolic hypoxic microenvironment. The synergistic mechanism of TPZ and SFB enhances the therapeutic effects of hypoxia-activated prodrugs and mitigates the adverse effects of hypoxia.

CAS / MDL: 284461-73-0
研究领域: 肿瘤学 · 药理学 · 介入放射学 · 药物递送系统
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Tailored platelet biomimetic delivery platform for targeted therapy of inflammatory bowel disease

Yue Li,Yayue Zhang,Xuran Ding,Taotao Zou,Hu Li,Ke Xu,Cheng Su,Yuting Wang,Ziming Zhao,Yuan He

Effective delivery of drugs to the inflamed colon is an attractive strategy for treating inflammatory bowel disease (IBD). Here we designed a drug delivery platform for IBD treatment by hybridizing platelet membrane (PM) with phosphatidylserine (PS)-containing liposomes (PM-Lipo). Introducing PM into hybrid nanovesicles enhanced their adhesion to the inflammatory endothelium in vitro , and increased their recruitment to the inflamed colon in a mouse IBD model. Meanwhile, adding PS into PM-Lipo improved macrophage targeting and uptake in vitro and in vivo . Rosiglitazone (ROSI) loading PM-Lipo (PM-Lipo-ROSI) effectively reprogrammed the pro-inflammatory macrophages towards an anti-inflammatory status in the inflamed colon, reducing pro-inflammatory cytokine secretion and immune cell infiltration. Moreover, PM-Lipo-ROSI also promoted the epithelial barrier regeneration of the damaged colon. The present study not only provides a novel paradigm for the precision treatment of IBD, but also lays a theoretical foundation for developing nanomedicines for other inflammatory diseases.

研究领域: 纳米医学 · 药物递送系统 · 炎症性疾病 · 生物医学工程 · 免疫治疗 · 胃肠病学
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RSC Advances · 2017 ·Vol. 7 ·期 34 ·20766-20778 · IF 3.108

Construction of biomimetic long-circulation delivery platform encapsulated by zwitterionic polymers for enhanced penetration of blood–brain barrier

Nan Wang,Xin Jin,Xinyuan Zhu

The effective treatments for central nervous system (CNS) diseases are impeded mostly by the existence of the blood–brain barrier (BBB). The accumulation of therapeutic drugs inside the brain is far from the therapy threshold, which is closely related to the transient circulation time of drugs and their carriers. Herein, a core–shell protein-based long-circulation delivery platform was constructed. Through in situ free radical polymerization, a zwitterionic polymer poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) was modified on the surface to prolong the circulation lifetime with a biomimetic structure induced by a phosphorylcholine (PC) head-group similar to the lipids in the outer membrane of living cells. A cell-penetrating peptide, HIV-1 trans-activating transcriptor (TAT) was conjugated on the surface of the protein-based nanoparticles, endowing the delivery platform with BBB-crossing ability. The BBB-permeability of the nanoparticles was investigated both in vitro and in vivo. Encapsulated with zwitterionic polymer PMPC, the nanoparticles showed a long circulation lifetime due to strong resistance to nonspecific adsorption and provided a better chance for BBB penetration. The delivery platform had enhanced permeability for BBB and a longer retention time inside the brain in a healthy mouse model. Overall, the surface modification with zwitterionic polymer PMPC and cell-penetrating peptide TAT changes the circulation modality of the nanoparticles in vivo, and provides a promising pathway for BBB crossing as a potential drug delivery platform for CNS related disease therapy.

研究领域: 药学 · 纳米技术 · 神经科学 · 药物递送系统
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