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ACS Biomaterials Science & Engineering · 2021 · IF 4.749

Aptamer and Peptide-Modified Lipid-Based Drug Delivery Systems in Application of Combined Sequential Therapy of Hepatocellular Carcinoma

Lv Jianghong,Meng Tingting,Zeng Yingping,Yu Tong,Zhao Lanxia,Liu Jingwen,Zhou Wentao,Chen Pengbo,Yuan Hong,Hu Fuqiang

Hepatocellular carcinoma (HCC) is known as the most common malignancy of the hepatobiliary system with a continued increase in incidence but limited therapeutic options. Nanomedicine has provided a promising strategy through engineered nanocarriers that are capable of targeting therapeutic agents specifically to tumor cells. In this research, two aptamer/peptide-modified lipid-based drug delivery systems (A54-PEG-SLN/OXA and A15-PEG-SLN/SAL) were developed as a sequential therapeutic strategy to conquer specific hepatocellular carcinoma. The nanomedicine A54-PEG-SLN/OXA was able to target specific hepatocellular carcinoma cell BEL-7402 and exhibited a strong targeting ability and antitumor efficiency both in vitro and in vivo. The A15-PEG-SLN/SAL could target and penetrate deeply to the spheroid composed of CD133+ cancer cells. In the study of developing a sequential therapeutic strategy, we demonstrated that A54-PEG-SLN/OXA could kill tumor cells and expose CD133+ cancer cells. After the administration of A15-PEG-SLN/SAL, the growth of the tumors was significantly inhibited. In conclusion, the aptamer/peptide-modified lipid-based drug delivery systems, A54-PEG-SLN/OXA and A15-PEG-SLN/SAL, could specifically target carcinoma cells and had an evident antitumor effect when administrated sequentially.

研究领域: 肿瘤学 · 药剂学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2025 · IF 5.7

Porous aromatic framework-based sequential therapeutic strategy for the treatment of periodontitis

Fuming Yang,Enpeng Xi,Yun Zhao,Gang Wang,Nan Gao,Guangshan Zhu

Periodontitis is a chronic inflammatory disease caused by the interaction between oral microorganisms and the host's immune response. The vicious cycle between bacterial infection and the host immune response renders any single treatment strategy ineffective. Therefore, a sequential approach that first rapidly eradicates pathogens, followed by anti-inflammatory therapy, is undoubtedly preferable. However, sequential release often needs to the release of several drugs in a controlled order over a long period of time, so it is necessary to rely on drug carriers, which must have a large drug loading capacity and maintain long-term stability. Compared to other drug carriers, the properties of porous aromatic frameworks (PAFs) precisely meet these requirements, and PAF-82 was employed. By sequentially loading diclofenac sodium (DS), coating with polydopamine (PDA) and adsorbing metronidazole (MTZ), PAF-DS@PDA-MTZ was constructed. The experimental results showed that PAF-DS@PDA-MTZ could quickly kill Porphyromonas gingivalis (P. g.) and eliminate ROS inhibition of pro-inflammatory factors, such as TNF-α and IL-6. Validation in a rat periodontitis model confirmed the system's efficacy in reducing alveolar bone resorption and enhancing periodontal healing efficiency. This strategy of coordinating antibacterial and anti-inflammatory effects through the temporal regulation of drug release provides a novel therapeutic approach for bacteria-driven diseases.

研究领域: 生物材料学 · 口腔医学 · 纳米医学 · 药剂学 · 免疫学 · 微生物学 · 转化医学
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Small · 2025 · IF 12.1

Electrospun Tri-Layer Core-Sheath Nanofibrous Coating for Sequential Treatment of Postoperative Complications in Orthopedic Implants

Yujie Hu,Feiyang Zhang,Jianfeng Zhou,Yi Yang,Deyi Ding,Mingzhang Li,Changming Wang,Boyong Wang,Jinlong Yu,Feng Jiang,Deng-Guang Yu,Hao Shen

The growing global prevalence of orthopedic conditions associated with an aging population has significantly increased the clinical demand for orthopedic implants. However, postoperative complications, including postoperative bleeding, implant associated infections (IAIs), and inadequate osteogenesis, continue to limit surgical outcomes. To simultaneously mitigate these challenges, a multifunctional electrospun fibrous coating (EFC) is developed, with an inner tri-layer core-sheath nanostructure to separately load tranexamic acid (TXA), fenoprofen (Fen), and puerarin (Pue) in the shell, middle, and core sections, respectively. Using poly(ε-caprolactone) (PCL) and polyvinylpyrrolidone (PVP) as polymeric matrices, tri-layer electrospun fibers are successfully fabricated, that spatially compartmentalize TXA, Fen, and Pue despite technical challenges. In vitro and in vivo studies demonstrated that TXA rapidly exerted hemostatic effects, effectively reducing initial postoperative bleeding. Subsequently, Fen suppressed the virulence of Staphylococcus aureus ( S. aureus ) by inhibiting the SaeRS two-component system, disrupting the biofilm barrier, and accelerating bacterial clearance by the host. Finally, Pue drove macrophage M2 polarization, which promoted angiogenesis and osteogenesis, ultimately supporting bone regeneration and long-term implant integration. EFC offers a promising sequential therapeutic strategy to address postoperative complications of orthopedic implant surgery. The protocol reported here exhibits a new way for developing novel medicated nanomaterials based on the distinct process-structure-performance relationship.

研究领域: 生物材料学 · 纳米医学 · 骨科学 · 感染控制 · 组织工程 · 药物递送系统 · 免疫调节 · 转化医学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biofabrication · 2025 ·Vol. 17 ·期 3 ·035031 · IF 8

Near-infrared light and magnetic field dual-responsive 3D printed scaffolds for sequential treatment of infected bone defects

Dapeng Zeng,Hao Wang,Zehao Yu,Xiaohan Mei,Boda Ying,Si Pu,Shibo Liu,Xiangjun Pan,Shicheng Zhou,Ruiyan Li,Yanguo Qin

The treatment of infected bone defects remains a challenge due to the complex biological processes involved, including antibacterial, anti-inflammatory, angiogenesis and bone regeneration. Polyetherimide (PEI) has promising applications in orthopaedics, but its biological inertness limits its clinical efficacy. In this study, a smart near-infrared (NIR) light and magnetic field responsive 3D printed scaffold was developed by combining PEI and Fe3O4 nanoparticles. Gelatin methacrylate hydrogel containing aloe-emodin (AE), a natural antimicrobial and antioxidant compound, was subsequently injected into the 3D printed scaffold to create the P–Fe3O4@GM–AE composite scaffold. This composite scaffold exhibited several key functionalities: Firstly, it effectively eliminated methicillin-resistant Staphylococcus aureus when exposed to NIR light, achieving an in vivo antimicrobial rate of 99.97 ± 0.1%. Secondly, it effectively removed reactive oxygen species and prevented the pro-inflammatory M1 polarization of macrophages in the infected bone defect microenvironment, creating favorable conditions for bone reconstruction. Moreover, during the reconstruction stage, the magnetic composite scaffold, when combined with a static magnetic field, promoted osteogenesis–angiogenesis coupling, thereby accelerating bone repair. Thus, this study provides new insights and methods for the sequential treatment of infected bone defects.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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Biomaterials Advances · 2024 · IF 5.5

Reactive oxide species and ultrasound dual-responsive bilayer microneedle array for in-situ sequential therapy of acute myocardial infarction

Qingqing Wang,Shuangyuan Cao,Teng Zhang,Fanzhen Lv,Mingfei Zhai,Danmeng Bai,Mengzhen Zhao,Haoxin Cheng,Xiaolei Wang

Acute myocardial infarction (AMI) resulting from coronary artery occlusion stands as the predominant cause of cardiovascular disability and mortality worldwide. An all-encompassing treatment strategy targeting pathological processes of oxidative stress, inflammation, proliferation and fibrotic remodeling post-AMI is anticipated to enhance therapeutic outcomes. Herein, an up-down-structured bilayer microneedle (Ce-CLMs-BMN) with reactive oxygen species (ROS) and ultrasound (US) dual-responsiveness is proposed for AMI in-situ sequential therapy. The upper-layer microneedle is formulated by crosslinking ROS-sensitive linker with polyvinyl alcohol loaded with cerium dioxide nanoparticles (CeNPs) featuring versatile enzyme-mimetic activities. During AMI acute phase, prompted by ischemia-induced microenvironmental redox imbalance, this layer swiftly releases CeNPs, which aid in eliminating excessive ROS and catalyzing oxygen gas (O 2 ) production through multiple enzymatic pathways, thereby alleviating oxidative stress-induced damage and modulating inflammation. In AMI chronic repair phase, micro-nano reactors (CLMs) situated in the lower-layer microneedle undergo cascade reactions with the assistance of US irradiation to generate nitric oxide (NO). As a bioactive molecule with pro-angiogenic and anti-fibrotic effects, NO expedites cardiac repair while attenuating adverse remodeling. Additionally, its antiplatelet-aggregating properties contribute to thromboprophylaxis. In-vitro and in-vivo results substantiate the efficacy of this integrated healing approach in AMI management, showcasing promising prospects for advancing infarcted heart repair.

研究领域: 心血管疾病 · 纳米技术 · 药物递送系统 · 生物医学工程 · 分子生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Multifunctional litchi husk nanocellulose-reinforced bidirectional polymeric hydrogel for sequential therapy of infected wound

Wenyuan Li,Lu Li,Jiahui Ou,Ying Wen,Xuan He,Dandan Li,Xianchun Hu,Yong Ye

The poor mechanical strength and singular therapeutic function of conventional hydrogel dressings have significantly constrained their clinical applicability for treating infected wounds. Consequently, the development of intelligent non-antibiotic dressings that exhibit both high mechanical strength and multiple synergistic therapeutic mechanisms represents a significant challenge. To address this, a “double polymerity-wide crosslinking” strategy was proposed in this work. This strategy successfully constructed a robust bidirectional polymeric hydrogel wound dressing reinforced with litchi husk cellulose nanofibrils. Specifically, the bidirectional polymerization of acrylamide was synergistically regulated by incorporating litchi shell extract and shell-derived cellulose microspheres, while also integrating the natural drug molecule epicatechin. Notably, the AgNPs encapsulated within the litchi shell extract endowed the dressing with remarkable antibacterial properties. Furthermore, the interpenetration of cellulose microspheres within the hydrogel network resulted in a structure exhibiting superior tensile strength, moderate viscosity, and commendable self-healing properties. Concurrently, interactions with the drug molecules facilitated a sequential controlled-release mechanism, enabling initial bacterial eradication followed by inflammation reduction. Molecular docking simulations effectively and sequencing of genes demonstrated stepwise drug delivery and mechanism of action. Moreover, in vivo wound healing experiments conducted on mice with epidermal infections confirmed the material's significant therapeutic efficacy.

研究领域: 生物材料 · 高分子科学 · 纳米技术 · 伤口愈合 · 药物递送系统 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Nano · 2023 · IF 17.1

Sequential Therapy for Bone Regeneration by Cerium Oxide-Reinforced 3D-Printed Bioactive Glass Scaffolds

Mengzhen Zhang,Xinyun Zhai,Tengfei Ma,Yongkang Huang,Mengdie Jin,Houzhi Yang,Hao Fu,Shuai Zhang,Tianwei Sun,Xin Jin,Yaping Du,Chun-Hua Yan

Rational design of multifunctional biomaterials with customized architecture and on demand bioactivity is of great significance for bone tissue engineering (BTE) in modern society. Herein, a versatile therapeutic platform has been established by integrating cerium oxide nanoparticles (CeO2 NPs) into bioactive glass (BG) to fabricate three-dimensional (3D)-printed scaffolds, achieving a sequential therapeutic effect against inflammation and promoting osteogenesis toward bone defect. The antioxidative activity of CeO2 NPs plays a crucial role in alleviating the oxidative stress upon formation of bone defects. Subsequently, CeO2 NPs exert a promotion effect on the proliferation and osteogenic differentiation of rat osteoblasts through enhancing mineral deposition and alkaline phosphatase and osteogenic gene expression. Strikingly, the incorporation of CeO2 NPs bestows on the BG scaffolds greatly reinforced mechanical properties, improved biocompatibility, adequate cell adhesion, elevated osteogenic capability, and multifunctional performance in a single platform. In vivo studies on the treatment of rat tibial defect confirmed the better osteogenic properties of CeO2–BG scaffolds compared with pure BG scaffolds. Additionally, the employment of the 3D printing technique creates a proper porous microenvironment around the bone defect, which further facilitates the cell in-growth and new bone formation. This report provides a systematic study on CeO2–BG 3D-printed scaffolds prepared by simple ball milling method, achieving sequential and integral treatment in BTE based on a single platform.

CAS / MDL: 64-19-7 67-68-5 127-09-3
研究领域: 材料科学 · 生物医学工程 · 组织工程 · 纳米技术 · 骨科
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