CHEMICAL ENGINEERING JOURNAL
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2021
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IF 13.273
Xinyu Jiang,Qing Yao,Xing Xia,Yingying Tang,Meng Sun,Yingtao Li,Hailun Zheng,Aimin Cai,Hailin Zhang,Vadivel Ganapathy,Ruijie Chen,Longfa Kou
Psoriasis is a chronic inflammatory skin disease with dysregulation of the immune system, which usually manifests as erythematous scleroma with hyperplasia of the epidermis. Although the pathogenesis remains unclear, oxidative stress and inflammation are inextricably linked during the development of psoriasis. Therefore, scavenging of ROS and suppression of inflammation may be a rational and effective strategy to ameliorate psoriasis and delay its further development. Here, a “Tanghulu”-like nanoplatform (BJN) is developed using the endogenous antioxidant bilirubin and a specific inhibitor (JPH203) of LAT1, an amino acid transporter involved in the activation of mTOR, for treatment of psoriasis by scavenging ROS and interfering with mTOR signaling, consequently blocking Th17 and IL-17 release. The nanoparticles show increased uptake in inflamed keratinocytes and display an efficient ROS scavenging capability. In an in vivo psoriasis model, BJN effectively permeate into the inflamed skin and be retained there, thereby reversing the psoriasis-specific changes in the imiquimod-induced mice as evident from suppression of keratinocyte hyperplasia and decrease in immune cell infiltration. This study shows that BJN can exert a superior anti-psoriasis effect by scavenging ROS, blocking the LAT1-mTOR pathway, inactivating immune reaction, restricting Th17 differentiation, and decreasing IL-17A secretion, offering a promising strategy for psoriasis treatment.
研究领域:
药学
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免疫学
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皮肤病学
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纳米技术
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分子生物学
✓ 已验证
DOI
高影响因子
Advanced Science
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2024
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IF 14.3
Huirong Huang,Shimin Zheng,Jianing Wu,Xindan Liang,Shengjie Li,Pengfei Mao,Zhinan He,Yahui Chen,Lining Sun,Xinyu Zhao,Aimin Cai,Luhui Wang,Huixiang Sheng,Qing Yao,Ruijie Chen,Ying-Zheng Zhao,Longfa Kou
Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease-modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G-conjugated bilirubin/JPH203 self-assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra-articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa-B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier-free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.
CAS / MDL:
研究领域:
风湿病学
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纳米技术
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免疫学
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药理学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Weiqi Zhang,Linjia Chen,Yahui Dong,Yinghua Zeng,Yongyu Chen,Yue Liu,Jingru Wang,Fujun Shi
Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to the lack of druggable targets and intrinsic resistance to conventional therapies. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a promising therapeutic vulnerability in TNBC. Here, we identify solute carrier family 7 member 5 (SLC7A5) as a ferroptosis-suppressing prognostic target, and develop a tumor microenvironment (TME)-responsive camptothecin (CPT)-peptide conjugates (CPCs) nanoassembly for in situ delivery of the SLC7A5 inhibitor JPH203 to TNBC. The CPCs integrate an active tumor targeting motif, a CPT-based hydrophobic core that drives self-assembly, and a gelatinase-cleavable linker for enzyme-responsive disassembly. Upon TME-triggered release, JPH203 effectively blocks leucine uptake, suppresses mTORC1 signaling, disrupts iron and redox homeostasis, and synergizes with mitochondrial reactive oxygen species to induce potent ferroptosis, achieving an 81.2% tumor growth suppression rate in orthotopic 4 T1 models with favorable biosafety. Importantly, CPCs-JPH promotes dendritic cell maturation, activates CD8 + T-cell responses, and significantly improves survival outcomes in orthotopic 4 T1 tumor-bearing mice. This work establishes a multifunctional and enzyme-responsive nanoplatform that harnesses ferroptosis to overcome therapeutic resistance while concurrently engaging innate and adaptive immunity in TNBC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
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2021
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IF 14.593
Longfa Kou,Xinyu Jiang,Yingying Tang,Xing Xia,Yingtao Li,Aimin Cai,Hailun Zheng,Hailin Zhang,Vadivel Ganapathy,Qing Yao,Ruijie Chen
Reprogramed cellular metabolism is one of the most significant hallmarks of cancer. All cancer cells exhibit increased demand for specific amino acids, and become dependent on either an exogenous supply or upregulated de novo synthesis. The resultant enhanced availability of amino acids supports the reprogramed metabolic pathways and fuels the malignant growth and metastasis of cancers by providing energy and critical metabolic intermediates, facilitating anabolism, and activating signaling networks related to cell proliferation and growth. Therefore, pharmacologic blockade of amino acid entry into cancer cells is likely to have a detrimental effect on cancer cell growth. Here we developed a nanoplatform ( [email protected] ) to therapeutically target two transporters, SLC6A14 (ATB 0,+ ) and SLC7A5 (LAT1), that are known to be essential for the sustenance of amino acid metabolism in most cancers. The [email protected] uses tryptophan to guide SLC6A14-targeted delivery of JPH203, a high-affinity inhibitor of SLC7A5. In the process, SLC6A14 is also down-regulated. We tested the ability of this strategy to synergize with the anticancer efficacy of lapatinib, an inhibitor of EGFR/HER1/HER2-assocated kinase. These studies show that blockade of amino acid entry amplifies the anticancer effect of lapatinib via interference with mTOR signaling, promotion of apoptosis, and suppression of cell proliferation and metastasis. This represents the first study to evaluate the impact of amino acid starvation on the anticancer efficacy of widely used kinase inhibitor.
研究领域:
肿瘤学
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药理学
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纳米技术
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2025
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IF 4
Tao Huang,Chunsu Liang,Jilun Li,Xiaomei Ling
High performance capillary electrophoresis (HPCE) has been widely applied in the analysis of amino acids (AAs), but no studies on the HPCE analysis of dissociated states of AAs have been reported. Here, twenty proteingenic AAs were analyzed by the newly-developed universal interface-induced current detector (IICRD). Two or three current signal peaks were observed in current electrophoretograms (CR-EGs), while only one peak with low sensitivity can be obtained by DAD. The current signal peaks of AAs were accurately identified by adding charge-neutral marker, comparing current signal peaks at different pH conditions, also calculating by p K a . The qualitative analysis indicated that the three current signal peaks of basic AAs were monovalent cations ([AA + ]), charge-neutral forms ([AA ± ]), and monovalent anions ([AA - ]) in order. Similarly, acidic AAs can be detected in three forms as [AA ± ], [AA - ] and [AA 2- ], while neutral AAs can be detected as [AA ± ] and [AA - ]. Quantitative analysis showed that HPCE-IICRD can enhance the sensitivity of AAs to 40 μmol/L in LOD, with a linear range from 10 –6 mol/L to 10 –2 mol/L. Furthermore, interactions between different dissociated states of twenty AAs and l -type amino acid transporter (LAT1) were studied by combined application of NICCE method for the first time. The binding kinetic parameters and mole number of LAT1 on cell membranes can also be obtained. Besides, competitive binding experiments proved that JPH203 (LAT1-specific inhibitor) and leucine shared the same binding site. HPCE-IICRD provides a new method to reveal the interaction between different dissociated forms of AAs or other biomolecules and essential receptors.
研究领域:
生物化学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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