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Biomedical Materials · 2024 ·Vol. 19 ·期 6 ·065033 · IF 3.9

Multifunctional nano co-delivery system for efficiently eliminating neuroblastoma by overcoming cancer heterogeneity

Shungen Huang,Xian Yang,Yajuan Gao,Haoying Huang,Tuanwei Li,Meng Li,Feng Wu,Hongcao Yang,Chunyan Li

The high heterogeneity of neuroblastoma (NB) is currently the main challenge in clinical treatment, impeding the complete eradication of the tumor through monotherapy alone. In this study, we propose a combination strategy using a targeted nano co-delivery system (ADRF@Ag2Se) comprising phototheranostic agents, differentiation inducers and chemotherapy drugs for sequential therapy of NB. Upon intravenous injection, ADRF@Ag2Se demonstrates effective tumor targeting by the specific binding of AF7P to MMP14, which is overexpressed on the surface of NB cells. Subsequent implementation of local photothermal therapy (PTT) leverages the robust photothermal conversion capabilities of the amphiphilic photothermal reagent PF. This is followed by the temperature-triggered release of differentiation-inducing agent 13-cis-retinoic acid and chemo-drug doxorubicin to synergistically eliminate the residual lesions. This nanotherapeutic strategy facilitates in vivo targeted delivery and PTT under the supervision of NIR-II fluorescence, and it also enhances the chemotherapeutic response through differentiation induction of poorly differentiated cancer cells. In the NB tumor model, this co-delivery strategy effectively inhibited tumor growth and significantly prolonged the survival of the mice.

CAS / MDL: 25316-40-9 4759-48-2
研究领域: 肿瘤学 · 纳米医学 · 生物医学工程
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Small · 2023 · IF 13.3

A Self-Assembly Nano-Prodrug for Combination Therapy in Triple-Negative Breast Cancer Stem Cells

Chongzhi Wu,Fu Zhang,Bowen Li,Zhiyao Li,Xin Xie,Yong Huang,Zhuo Yao,Yuan Chen,Yuan Ping,Weidong Pan

Triple-negative breast cancer (TNBC) displays a highly aggressive nature that originates from a small subpopulation of TNBC stem cells (TNBCSCs), and these TNBCSCs give rise to chemoresistance, tumor metastasis, and recurrence. Unfortunately, traditional chemotherapy eradicates normal TNBC cells but fails to kill quiescent TNBCSCs. To explore a new strategy for eradicating TNBCSCs, a disulfide-mediated self-assembly nano-prodrug that can achieve the co-delivery of ferroptosis drug, differentiation-inducing agent, and chemotherapeutics for simultaneous TNBCSCs and TNBC treatment, is reported. In this nano-prodrug, the disulfide bond not only induces self-assembly behavior of different small molecular drug but also serves as a glutathione (GSH)-responsive trigger in controlled drug release. More importantly, the differentiation-inducing agent can transform TNBCSCs into normal TNBC cells, and this differentiation with chemotherapeutics provides an effective approach to indirectly eradicate TNBCSCs. In addition, ferroptosis therapy is essentially different from the apoptosis-induced cell death of differentiation or chemotherapeutic, which causes cell death to both TNBCSCs and normal TNBC cells. In different TNBC mouse models, this nano-prodrug significantly improves anti-tumor efficacy and effectively inhibits the tumor metastasis. This all-in-one strategy enables controlled drug release and reduces stemness-related drug resistance, enhancing the chemotherapeutic sensitivity in TNBC treatment.

研究领域: 肿瘤学 · 药学 · 纳米技术 · 癌症生物学
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Frontiers in Bioengineering and Biotechnology · 2021 · IF 5.89

ROS-Sensitive Nanoparticles Co-delivering Dexamethasone and CDMP-1 for the Treatment of Osteoarthritis Through Chondrogenic Differentiation Induction and Inflammation Inhibition

Wu Xiaodong,Li Pengpeng,Cheng Jian,Xu Qiang,Lu Beiji,Han Conghui,Huo Weiling

Objective: Osteoarthritis (OA) is a common subtype of arthritis. To date, treatment of OA focuses primarily on alleviating pain and improving joint function. The lack of a vascular system within synovial joints and the rapid removal of agents due to synovial exchange hinder continuous delivery of OA drugs. However, these obstacles are being addressed by promising nanoscale drugs.Methods: We synthesize and assemble a hydrogen peroxide [H2O2, belongs to the category of active oxygen species (ROS)]-sensitive nanomicelle, which is loaded with the anti-inflammation drug dexamethasone and chondrogenic differentiation factor cartilage-derivedmor-phogeneticprotein-1. The micelle can induce bone marrow mesenchymal stem cells to repair cartilage while inhibiting joint inflammation.Results: The prepared nanoparticles were of uniform size and displayed an obvious core-shell structure. Under H2O2 stimulation, the shell layer could be removed gradually. The drug-loaded micelle effectively inhibited proliferation of activated macrophages, induced macrophage apoptosis with an anti-inflammatory effect, and caused the BMSCs to differentiate into chondrocytes.Conclusion: This work provides an experimental and theoretical basis for further development of a drug-loaded micelle in the healing of osteoarthritis.

研究领域: 药学 · 生物医学工程 · 骨科 · 纳米技术
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Journal of Materials Chemistry B · 2019 ·Vol. 7 ·期 44 ·7052-7064 · IF 5.047

Dually optimized polycaprolactone/collagen I microfiber scaffolds with stem cell capture and differentiation-inducing abilities promote bone regeneration

Hui Chi,Anlong Jiang,Xiaoyan Wang,Guanghua Chen,Chengchao Song,Ravi Kumar Prajapati,Ang Li,Zecheng Li,Jiaxin Li,Zhengye Zhang,Ye Ji,Jinglong Yan

Micro–nano based fibrous scaffolds have been extensively studied in regenerative medicine. Bone marrow stem cells (BMSCs) and BMP2-derived peptides, two other important components for tissue engineering, have been successfully used for bone regeneration. However, a scaffold that specifically captures BMSCs and delivers BMP2-derived peptides to promote osteogenic differentiation of enriched BMSCs has not been reported. In this study, a microfiber scaffold was constructed by coaxial electrospinning technology using a polyvinylpyrrolidone/bovine serum albumin/BMP2-derived peptide compound as the core solution and a polycaprolactone/collagen I compound as the shell solution. The scaffolds were further functionalized by covalent grafting of a BMSC affinity peptide (E7) to develop a dual drug release system for the delivery of the BMP2-derived peptide and E7. Structural analysis indicated that the microfibers had a uniform diameter and homogeneous core–shell structure. Fourier transform infrared spectroscopy (FTIR) revealed that E7 was covalently bonded onto the surface of the fibers. In vitro, the E7-modified scaffolds promoted the initial adhesion of BMSCs and were more favorable for BMSC survival. Furthermore, the BMP2-derived peptide loaded in the E7-modified scaffolds was released in a sustained manner and retained bioactivity, significantly improving the osteogenic differentiation of BMSCs. In vivo, scaffolds loaded with the BMP2-derived peptide and E7 (PCME scaffolds) led to enhanced new bone formation and defect closure in a rat calvarial defect model. Overall, the PCME scaffold simultaneously facilitated all three of the essential elements needed for bone tissue engineering, providing a promising method for bone regeneration.

研究领域: 再生医学 · 组织工程 · 生物材料科学 · 干细胞生物学
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Advanced Healthcare Materials · 2020 ·Vol. 9 ·期 23 ·2000076 · IF 7.367

A Biomimetic Biphasic Osteochondral Scaffold with Layer-Specific Release of Stem Cell Differentiation Inducers for the Reconstruction of Osteochondral Defects

Xuemin Liu,Yingqi Wei,Chengkai Xuan,Lei Liu,Chen Lai,Muyuan Chai,Zhaoguo Zhang,Lin Wang,Xuetao Shi

There is a great challenge in regenerating osteochondral defects because they involve lesions of both cartilage and subchondral bone, which have remarkable differences in their chemical compositions and biological lineages. Thus, considering the complicated requirements in osteochondral reconstruction, a biomimetic biphasic osteochondral scaffold (BBOS) with the layer-specific release of stem cell differentiation inducers are developed. The cartilage regeneration layer (cartilage scaffold, CS) in the BBOS contains a hyaluronic acid hydrogel to mimic the composition of cartilage, which is mechanically enhanced by host–guest supramolecular units to control the release of kartogenin (KGN). Additionally, a 3D-printed hydroxyapatite (HAp) scaffold releasing alendronate (ALN) is employed as the bone-regeneration layer (bone scaffold, BS). The two layers are bound by semi-immersion and could regulate the hierarchical targeted differentiation behavior of the stem cells. Compared to the drug-free scaffold, the MSCs in the BBOS could be promoted to differentiate into both chondrocytes and osteoblasts. The in vivo results demonstrate the strong promotion of cartilage or bone regeneration in their respective layers. It is expected that this BBOS with layer-specific inducer release can become a new strategy for osteochondral regeneration.

CAS / MDL: 7585-39-9
研究领域: 组织工程 · 再生医学 · 生物医学工程 · 骨科
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