Nanoscale
·
2020
·Vol. 12
·期 46
·23756-23767
·
IF 6.895
Chao Teng,Beiyuan Zhang,Zhongyue Yuan,Zheng Kuang,Zhuodong Chai,Lianjie Ren,Chao Qin,Lei Yang,Xiaopeng Han,Lifang Yin
Cancer-associated fibroblasts (CAFs) are the majority cell population of tumor stroma, and they not only play important roles in tumor growth and metastasis, but they also form a protective physical barrier for cancer cells. Herein, we designed a fibroblast activation protein-α (FAP-α)-adaptive polymeric micelle based on hyaluronic acid and curcumin conjugates. The polymeric micelle is composed of a CD44-targeting shell and a FAP-α-cleavable polyethylene glycol (PEG) coating. When FAP-α is encountered on the surface of CAFs in the tumor microenvironment, the PEG layer is released, hyaluronic acid is recovered on the surface of nanoparticles, and the nanoparticles effectively inhibit the growth of tumor cells and CAFs through CD44-mediated endocytosis. The FAP-α-adaptive polymeric micelle exhibited potent anti-cancer efficacy by enhancing CAF apoptosis and reducing collagen in tumor tissues. Collectively, FAP-α-adaptive nanoparticles may be a promising method for antitumor anticancer treatments via reprogramming of stroma fibrosis.
研究领域:
药学
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肿瘤学
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纳米技术
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生物材料科学
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DOI
PubMed
高影响因子
LANGMUIR
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2024
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IF 3.7
Jieheng Zhang,Jianchang Xu,Jiaying Zhang,Yibin Lin,Jiaxin Li,Duoqu Chen,Wenjing Lin,Chufen Yang,Guobin Yi
It is crucial to use simple methods to prepare stable polymeric micelles with multiple functions for cancer treatment. Herein, via a “bottom-up” strategy, we reported the fabrication of β-CD-(PEOSMA-PCPTMA-PPEGMA)21 (βPECP) unimolecular micelles that could simultaneously treat tumors and bacteria with chemotherapy and photodynamic therapy (PDT). The unimolecular micelles consisted of a 21-arm β-cyclodextrin (β-CD) core as a macromolecular initiator, photosensitizer eosin Y (EOS-Y) monomer EOSMA, anticancer drug camptothecin (CPT) monomer, and a hydrophilic shell PEGMA. Camptothecin monomer (CPTMA) could achieve controlled release of the CPT due to the presence of responsively broken disulfide bonds. PEGMA enhanced the biocompatibility of micelles as a hydrophilic shell. Two βPECP with different lengths were synthesized by modulating reaction conditions and the proportion of monomers, which both were self-assembled to unimolecular micelles in water. βPECP unimolecular micelles with higher EOS-Y/CPT content exhibited more excellent 1O2 production, in vitro drug release efficiency, higher cytotoxicity, and superior antibacterial activity. Also, we carried out simulations of the self-assembly and CPT release process of micelles, which agreed with the experiments. This nanosystem, which combines antimicrobial and antitumor functions, provides new ideas for bacteria-mediated tumor clinical chemoresistance.
研究领域:
纳米技术
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药学
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生物医学工程
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癌症研究
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微生物学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2024
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IF 8
Siyi Li,Kexin Li,Xianfeng Gong,Pengfei Yan,Shaoping Sun
Multifunctional polymeric micelles, which possess capabilities for tracking, bioimaging, stimuli-responsive drug release and tumor targeting, are essential in facilitating the effective delivery of anticancer drugs. Hence, a novel copolymer (CD-CS-Bio-TPAA, CCBT) was synthesized with biotin and hydroxypropyl-β-cyclodextrin conjugated chitosan as the hydrophilic segment and aggregation-induced emission (AIE) featured tetraphenylethene derivative (TPAA) as the hydrophobic segment. Interestingly, under acidic conditions, CCBT exhibited color-tunable AIE behavior as a result of the cleavage of benzoic imine bonds in TPAA molecules, transitioning from red to yellow. Furthermore, CCBT could also self-assemble into polymeric micelles and be used as drug carriers to encapsulate paclitaxel (PTX) (PTX/CCBT PMs) for self-indicating cancer therapy. In vitro release experiments demonstrated that PTX/CCBT PMs could release drugs specifically under acidic conditions. Fluorescence imaging experiments demonstrated that CCBT PMs exhibited excellent cell imaging capabilities and could be tracked due to their unique color-changing behavior. Moreover, PTX/CCBT PMs exhibited notable cytotoxic effects on MCF-7 cells and showed selective internalization by MCF-7 cells through biotin receptor-mediated active targeting. In vivo antitumor experiments confirmed that PTX/CCBT PMs possessed remarkable tumor-inhibiting effects and low systemic toxicity. This work suggested that PTX/CCBT PMs provided new ideas for self-indicating breast cancer treatment.
研究领域:
生物材料
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肿瘤学
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药剂学
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产品关联
DOI
高影响因子
ACS Applied Nano Materials
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2024
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IF 5.3
Sifang Zhao,Fengjiao Chen,Xianwu Chen,Hongze Liang,Hui Tan,Lingling Zhao
The tumor microenvironment is characterized by several hallmarks such as an acidic pH and high glucose levels in tumor tissues and increased expression of specific proteins and/or sugars on the surface of tumor cells. These unique hallmarks of tumors can be considered in the design of multifunctional drug delivery nanosystems to improve the efficiency of tumor therapy through targeted drug delivery and specific drug release in the tumor tissue. In this study, phenylboronic acid-modified pH- and glucose-responsive polymer micelles were designed for the targeted delivery of anticancer drugs. The polymeric micelles demonstrated prolonged and pH/glucose-triggered drug release and enhanced cellular internalization by B16F10 cells through a receptor-mediated endocytosis pathway. The polymeric micellar system could inhibit the proliferation of B16F10 cells with IC50 values lower than those of unmodified micelles. In addition, the polymeric micellar system could markedly suppress cell migration, colony formation, and invasion and promote the apoptosis of B16F10 cells, indicating good anticancer efficiency in vitro. Therefore, this polymeric nanocarrier provides a potential platform for targeted anticancer therapy.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Mo Liu,Zi-xu Zhang,Jia-hua Wang,Rui-bo Guo,Lu Zhang,Liang Kong,Yang Yu,Juan Zang,Yang Liu,Xue-tao Li
Ovarian cancer, a highly lethal form of gynecological cancer globally, has witnessed notable advancements in its treatment through the integration of nanotechnology and immunotherapy. Here, we designed a novel astragalus polysaccharide vector (PDA), encapsulating podophyllotoxin (PPT), and modifying methotrexate (DSPE-PEG 2000 -MTX) on its surface for targeting ovarian cancer cells with high folate receptor expression. We prepared novel MTX-modified PPT-loaded astragalus polysaccharide micelles (MTX-PPT-micelles) by dialysis method and evaluated their characterization, stability, safety and targeting ability. EDU proliferation, apoptosis, wound healing, and macrophage polarization experiments were performed, and a mouse ectopic tumor model and a lung metastasis model were established to evaluate the antitumor effects of MTX-PPT-micelles. The prepared MTX-PPT-micelles had appropriate particle size, good stability and safety, and were able to achieve slow drug release. In vitro and in vivo experiments showed that MTX-PPT-micelles significantly enhanced tumor uptake and apoptosis, and significantly inhibited tumor proliferation, invasion and metastasis processes. In addition, MTX-PPT-micelles could improve tumor immunosuppression by shifting tumor-associated macrophages from M2 to M1 phenotype. In conclusion, this study successfully constructed a novel nano-delivery system to achieve targeted therapy for ovarian cancer by combating tumor cells with immunomodulatory effects on tumor-associated macrophages.
研究领域:
肿瘤学
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药剂学
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免疫学
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产品关联
DOI
PubMed
高影响因子
ACS Omega
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2024
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IF 3.7
Hui-Qin Liu,Xi-Dong Wu,Xue-Wen Fang,Yun-Song An,Meng Xia,Xiao-Hua Luo,Jun-Zheng Li,Guan-Hai Wang,Tao Liu
Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. Unfortunately, current treatments encounter multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), resulting in the efflux of chemotherapy drugs, is one of the significant mechanisms causing MDR. d-α-Tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) has been demonstrated to effectively inhibit P-gp expression. The objectives of this study are to improve tumor MRI imaging, optimize docetaxel (DOC) administration, and target P-gp to overcome NPC resistance. Multifunctional micelles of TPGS (MM@DOC), loaded with magnetic nanoparticles, were synthesized for the targeted delivery of the first-line anticancer drug. MM@DOC exhibited greater toxicity and induced higher levels of apoptosis in DOC-resistant NPC cells (C666–1/DOC) compared to DOC. MM@DOC loaded with magnetic nanoparticles improved the quality of tumor MRI imaging. MM@DOC also demonstrated significant antitumor effects in nude mice with C666–1/DOC NPC. In conclusion, MM@DOC exhibited promising inhibitory effects on resistant tumors both in vitro and in vivo, optimized tumor MRI imaging, and showed great potential in drug delivery and overcoming resistance.
研究领域:
肿瘤学
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医学影像学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2026
·
IF 6
Chunpeng Yang,Mengdi Wu,Min Li,Wenbin Niu,Yinan Zhao,Shubiao Zhang
MST and CD quantitatively confirmed that the flexible ADH-DTDPA spacer preserves strong CD44 binding ( K D = 15.3 μM). • HPMs showed pH/redox-triggered release, with 78.2% payload release in 72 h under tumor-mimicking conditions. • HPMs achieved superior antitumor efficacy at a lower dose while reducing systemic toxicity in vivo . Clinical application of podophyllotoxin (PPT) is significantly hampered by poor aqueous solubility and considerable systemic toxicity. Herein, we engineered dual-targeting and dual-cleavable prodrug micelles (HPMs) by conjugating PPT to hyaluronic acid (HA) backbone via a flexible, dual-responsive spacer, adipic dihydrazide–3,3′-dithiodipropionic acid (ADH-DTDPA). In vitro , HPMs demonstrated efficient CD44-mediated internalization in NCI-H1299 cells and rapidly disassembled under tumor microenvironment (TME) conditions (pH 5.0/GSH). Crucially, microscale thermophoresis (MST) provided quantitative evidence of the targeting mechanism, revealing a high binding affinity ( K D = 15.3 μM) for the CD44 receptor. In vivo , this design achieved effective accumulation of the micelles at tumor sites. Notably, HPMs (10 mg/kg) achieved superior tumor inhibition compared to free PPT (15 mg/kg) without inducing hepatotoxicity or nephrotoxicity. These findings provide a safe delivery strategy to overcome the clinical limitations of PPT and offer quantitative molecular insights into the rational design of targeted nanomedicines for lung cancer therapy. Download: Download high-res image (244KB) Download: Download full-size image
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DOI
PubMed
高影响因子
Acta Biomaterialia
·
2026
·
IF 10.4
Xiangrong Dai,Yi Liao,Rong Chen,Xuanxiang Jin,Jiajia Dong,Ying Tan,Xuru Jin
Nebulized inhalation represents an attractive approach for pulmonary drug delivery due to its non-invasiveness and direct lung targeting capability. However, the effectiveness of conventional inhaled formulations is limited by their inability to simultaneously evade mucociliary clearance and macrophage phagocytosis, leading to suboptimal lung retention and low bioavailability. To address these challenges, a series of ultra-small zwitterionic "camouflage" micelles, Distearoylphosphatidylethanolamine (DSPE)-block-poly ( N -methacryloyloxyethyl- N, N -dimethylammonium-α-N-methylcarboxybetaine) (CB) (D-PCB n ), were developed to synergize biomimetic targeting with enhanced mucosal penetration. The micelles feature a DSPE-based core structurally modeled after dipalmitoylphosphatidylcholine (DPPC), a key pulmonary surfactant lipid, enabling biomimetic alveolar targeting. Simultaneously, a carboxybetaine-derived corona facilitates robust hydration-mediated surface lubrication for efficient mucus penetration. Among the series, the optimized D-PCB 30 variant exhibited superior mucus-permeating capacity, enhanced pulmonary deposition, and high encapsulation efficiency for dexamethasone. In vivo evaluation in a murine model following aerosol administration demonstrated significantly improved lung accumulation, extended residence time, reduced systemic distribution, and enhanced anti-inflammatory efficacy. Transcriptomic analysis further indicated modulation of critical inflammatory pathways and reprogramming of macrophage polarization (M1 to M2 phenotype), corroborating the therapeutic benefits achieved through enhanced barrier penetration. These results demonstrate the potential of D-PCB n micelles as a promising inhalable nanoplatform for targeted treatment of lung diseases. Statement of Significance Delivering therapeutics to injured lungs is hampered by mucus barriers, rapid clearance, and immune sequestration. Here, we describe ultra-small, biomimetic zwitterionic micelles D-PCBMA n (D-PCB 30 ) that combine a DPPC-mimetic DSPE core with a carboxybetaine corona to create a “camouflage-and-lubricate” nanoplatform. D-PCB 30 exhibits a low critical micelle concentration (CMC), high drug loading, and stability upon nebulization, enabling deep mucus penetration, reduced macrophage uptake, and sustained pulmonary residence. When loaded with dexamethasone (DEX) and delivered by nebulization, D-PCB 30 increases local drug deposition while reducing systemic exposure, resulting in potent attenuation of LPS-driven inflammation, preservation of alveolar architecture, and diminished fibrotic remodeling. Mechanistically, transcriptomic profiling reveals suppression of TLR/MyD88/NF-κB inflammatory circuits and induction of tissue-repair programs, alongside a shift in macrophage phenotype toward resolution. With an encouraging biosafety profile and mitigated steroid side effects, D-PCB 30 represents a clinically promising strategy to overcome pulmonary barriers and to deliver targeted, effective therapies for acute inflammatory lung disease.
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DOI
高影响因子
FOOD CHEMISTRY
·
2026
·
IF 10.4
Hongkai Zhang,Jiangping Ye,Shunjing Luo,Xiuting Hu,Chengmei Liu
Acidification at 90 °C prevented whey separation in acidified milk. • Acidification at 90 °C enhanced the gel strength and viscosity of acidified milk. • Fibrils appeared in the acidified milk obtained at 90 °C. • When casein micelles were acidified at 90 °C, fibrillation occurred. • Fibrillation of casein micelles improved the acidified milk stability. Whey separation usually occurs to traditional acidified milk beverages. Therefore, this work aimed to improve stability of acidified milk beverages through high-temperature acidification, because high-temperature acidification might induce fibrillation of milk protein. The stability was enhanced when milk was acidified at 90 °C. Atomic force microscopy analysis revealed that the traditional acidified milk gel was particulate, whereas fibrils appeared in acidified milk obtained at 90 °C. Moreover, when the whey protein solution and the casein micelle suspension were acidified at 90 °C, respectively, no fibrils were observed in the whey protein solution, while casein micelles became fibrils. These results suggested acidification at 90 °C mainly induced casein fibrillation and thus improved stability of acidified milk. Thioflavin T fluorescence showed that longer treatment time enhanced casein fibrillation, which aligned with improved stability of acidified milk products at 90 °C through extended acid-heat treatment. This correlation also suggested that casein fibrillation enhanced acidified milk stability. Acidification at 90 °C for ≥3 h induced fibrillation of casein micelles and improved the acidified milk stability. Download: Download high-res image (105KB) Download: Download full-size image
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DOI
PubMed
高影响因子
MACROMOLECULES
·
2024
·
IF 5.1
Yanran Li,Jun Ma,Yanbin Fan,Chen Zheng,Daoyong Chen
Structures impact the performance of nanocatalysts, but optimizing them by altering their structures is tedious and restricted. We present a strategy using “high energy” polymeric composite micelles as precursors to produce variously structured nanocatalysts in a simple, temporally controlled manner. By incubating core–shell spherical micelles of poly(ethylene glycol)-b-poly(4-vinylpyridine) with a molybdate hydrate complexable with poly(4-vinylpyridine), the molybdates cross-link and enlarge the confined poly(4-vinylpyridine) core, producing “high-energy” and “crosslinking-locked” polymeric composite micelles. Properly increasing the temperature weakens the cross-linking and releases the energy at a suitable rate, facilitating the stepwise transition of the polymeric composite micelles into various structures. Cooling the system at specific phases generates worm-like, flower-like, and clustered structures that further develop into molybdenum phosphide (MoP) nanoworms, nanoflowers, and nanoclusters, respectively. MoP nanoworms demonstrate the highest efficiency as nanoelectrocatalysts for hydrogen evolution, surpassing previously reported MoP-based catalysts and even commercial Pt/C catalysts in high current density regions.
研究领域:
材料科学
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化学工程
·
纳米技术
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Zhouchun Chen,Qingshan Yang,Mengyu Fan,Tianran Chai,Yang Liu,Xue Xia,Muhammad Ismail,Meng Zheng
Targeting mitochondrial-mediated energy metabolism has emerged as a promising therapeutic strategy for glioblastoma multiforme (GBM), given its crucial role in sustaining the rapid growth and survival of tumor cells. In this study, we developed a combinatory, non-cationic siRNA-conjugated self-assembled micelle system core-encapsulated with Gboxin (siRNA-micelle@Gboxin) designed to induce severe mitochondrial dysfunction in GBM cells. The mTOR-siRNA component in the micelle silences mTOR expression, downregulates mTORC1 activity, and reduces 4EBP1 phosphorylation, leading to inhibition of mRNA translation and disruption of cellular energy metabolism, ultimately resulting in decreased ATP production. Concurrently, the GBM-specific drug Gboxin inhibits oxidative phosphorylation (OXPHOS), directly inducing mitochondrial dysfunction and exacerbating the energy crisis within glioma cells, synergistically accelerating apoptosis through mitochondrial damage. Notably, this dual-target inhibition of mTORC1 and OXPHOS by siRNA-micelle@Gboxin resulted in a more potent, synergistic anti-tumor effect than targeting either pathway alone. These findings highlighted that the Gboxin-loaded siRNA micelle offers a promising and innovative nanotherapeutic approach for GBM treatment, harnessing the synergistic effects of gene silencing and chemotherapy-based mitochondrial disruption to achieve a powerful therapeutic efficacy.
研究领域:
肿瘤学
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纳米医学
·
分子生物学
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癌症代谢
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基因治疗
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2025
·
IF 5.4
Peng Li,Lei Wang,Gui-qiang Fei,Hua-qiang Shi,Rong Wang,Jin-hao Gao,Zhi-qiang Dang,Xu-jie Lin,Jia-li Chen,Xiao-juan Lai
The micelle behavior between surfactants and hydrophobic associative polymers solves the problem of temperature resistance of self-thickening acids. Gemini betaine 2C 12 -SGS is synthesized from N-[3-(dimethylamino)propyl] lauramide, sodium 3-chloro-2-hydroxy-propanesulfonate, and 1,4-dibromobutane. When Gemini Betaine 2C 12 -SGS was added to the ADOM acid solution, the residual viscosity of the residual acid solution was 103 and 55.67 mPa·s after shearing for 1 h at 150 °C and 180 °C, respectively, which increased by 41.64 and 32.74 mPa·s, respectively, and increased by 67.86% and 142.78%, respectively, compared with those without surfactant. The interaction between surfactants and self-thickening acids provides theoretical support for their composite system to serve as an acidizing fluid for high-temperature carbonate reservoirs.
研究领域:
胶体与界面化学
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石油工程材料
·
高分子物理
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油田化学
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流变学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）