CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Yanmei Li,Junmei Nie,Xinyu Li,Ni Yan,Renjiang Kong,Jiaqi Huang,Yeyang Wu,Zhuofeng Li,Yingtao Zhong,Xin Chen,Hong Cheng
Stimulator of interferon genes (STING) plays an essential role in initiating the innate anti-tumor immunity, which could be activated by the cytosolic DNA but suppressed by the immunosuppressive cells. In this work, a self-delivery ternary immunostimulant (designated as ImmSt) is fabricated for colorectal cancer therapy with the immunological cascades of photodynamic DNA damage and T regulatory cell inhibition. Among which, the photosensitizer of Chlorin e6 (Ce6), the STING agonist of 5,6-dimethylxanthine-4-acetic acid (DMXAA) and the phosphatidylinositol 3-kinases (PI3Ks) inhibitor of ZSTK474 could self-assemble into uniform nanomedicine without drug excipient, which enhances the drug stability, bioavailability and pharmacological activities. Importantly, the photodynamic therapy (PDT) effect of ImmSt produces enormous reactive oxygen species to ablate tumor cells, and also triggers the release of cytosolic DNA to amplify the STING signal in combination with the STING agonist. Moreover, ImmSt is able to induce a systemic anti-tumor immunity by the cascade activation of T cells and the decrease of T regulatory cells. In vitro and in vivo results confirm that ImmSt can efficiently eradicate colorectal cancer without severe side effects, which may provide a sophisticated mechanism for immunotherapy in consideration of the immune activation and immunosuppressive factors.
研究领域:
肿瘤学
·
免疫疗法
·
药理学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Mengyang Zhou,Yifei Wang,Yaning Xia,Yinhua Li,Jianfeng Bao,Yong Zhang,Jingliang Cheng,Yupeng Shi
Nanotechnology for tumor diagnosis and optical therapy has attracted widespread interest due to its low toxicity and convenience but is severely limited due to uncontrollable tumor targeting. In this work, homologous cancer cell membrane-camouflaged multifunctional hybrid metal coordination nanoparticles (DRu/Gd@CM) were prepared for MRI-guided photodynamic therapy (PDT) and photothermal therapy (PTT) of tumors. Bimetallic coordination nanoparticles are composed of three functional modules: dopamine, Ru(dcbpy) 3 Cl 2 and GdCl 3 , which are connected through 1,4-Bis[(1H-imidazole-1-yl)methyl]benzene (BIX). Their morphology can be easily controlled by adjusting the ratio of precursors. Optimistically, the intrinsic properties of the precursors, including the photothermal properties of polydopamine (PDA), the magnetic resonance (MR) response of Gd 3+ , and the singlet oxygen generation of Ru(dcbpy) 3 Cl 2 , are well preserved in the hybrid metal nanoparticles. Furthermore, the targeting of homologous cancer cell membranes enables these coordinated nanoparticles to precisely target tumor cells. The MR imaging capabilities and the combination of PDT and PTT were demonstrated in in vitro experiments. In addition, in vivo experiments indicated that the nanoplatform showed excellent tumor accumulation and therapeutic effects on mice with subcutaneous tumors, and could effectively eliminate tumors within 14 days. Therefore, it expanded the new horizon for the preparation of modular nanoplatform and imaging-guided optical therapy of tumors.
研究领域:
纳米技术
·
生物医学工程
·
癌症治疗
·
分子成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2018
·
IF 13.709
Jing Zuo,Langping Tu,Qiqing Li,Yansong Feng,Ivo Que,Youlin Zhang,Xiaomin Liu,Bin Xue,Luis J. Cruz,Yulei Chang,Hong Zhang,Xianggui Kong
Photoswitchable materials are important in broad applications. Recently appeared inorganic photoswitchable upconversion nanoparticles (PUCNPs) become a competitive candidate to surmount the widespread issue of the organic counterparts —photobleaching. However, current PUCNPs follow solely Yb3+/Nd3+ cosensitizing mode, which results in complex multilayer doping patterns and imperfectness of switching in UV–blue region. In this work, we have adopted a new strategy to construct Nd3+ free PUCNPs—NaErF4@NaYF4@NaYbF4:0.5%Tm@NaYF4. These PUCNPs demonstrate the superior property of photoswitching. A prominent UV–blue emission from Tm3+ is turned on upon 980 nm excitation, which can be completely turned off by 800 nm light. The quasi-monochromatic red upconversion emission upon 800 nm excitation—a distinct feature of undoping NaErF4 upconversion system—endows the PUCNPs with promising image-guided photoinduced “off–on” therapy in biomedicine. As a proof-of-concept we have demonstrated the imaging-guided photodynamic therapy (PDT) of cancer, where 800 nm excitation turns off the UV–blue emission and leaves the emission at 660 nm for imaging. Once the tumor site is targeted, excitation switching to 980 nm results in UV–blue emission and the red emission. The former is used to induce PDT, whereas the latter is to monitor the therapeutic process. Our study implies that this upconversion photoswitching material is suitable for real-time imaging and image-guided therapy under temporal and spatial control.
研究领域:
材料科学
·
生物医学工程
·
纳米技术
·
诊疗学
·
光学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2021
·
IF 8.128
Huaying Hou,Zhongxu Wang,Yajie Ma,Kai Yu,Jingxiang Zhao,Huiming Lin,Fengyu Qu
The intracellular O 2 -supply not only can relieve tumor hypoxia but also enhance the effects of photodynamic therapy (PDT). In this work, metallic Mo 2 [email protected] N [email protected] nanoparticles were constructed to reveal the near infrared (NIR)-photocatalytic O 2 generation and promote photodynamic therapy (PDT). Here, (NH 4 ) 6 Mo 7 O 24 ·4H 2 O nanorods and urea were adopted as resources that were calcined to obtain Mo 2 [email protected] N -carbon nanoparticles (20 nm). All samples displayed high NIR absorption as well as photothermal conversion efficiency of up to 52.7 % (Mo 2 [email protected] N [email protected] ). The density functional theory calculations demonstrated the metallic characteristic of Mo 2 C and that the consecutive interband/intraband charge-transition was responsible for the high NIR harvest and redox ability of electron-hole pairs, making the NIR-photocatalytic O 2 and reactive oxygen species (ROS) generation. In comparison with the pure Mo 2 C, the heterostructure displayed twice the performance due to the enhanced charge-segregation between Mo 2 C and N -carbon. Given the high X-ray absorption coefficient and photothermal ability, the nanocomposite could be used in novel computer tomography and photothermal imaging contrast. Furthermore, the novel biodegradation and metabolism behaviors of nanocomposites were investigated, which were reflected as elimination from the body (mouse) via feces and urine within 14 days. The as-synthesized Mo 2 [email protected] N [email protected] nanocomposites integrated the dual-model imaging, intracellular O 2 -supply, and phototherapy into one nanoplatform, revealing its potential for anti-cancer therapy.
研究领域:
生物医学工程
·
材料科学
·
纳米技术
·
癌症治疗
·
成像技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Qiqi Yin,Yanli Yao,Handan Zhang,Jie Zhang,Jiaming Gao,Lin Weng,Tao Liu,Shuyang Sun,Xin Chen
The management of oral squamous cell carcinoma (OSCC) poses significant challenges, leading to organ impairment and ineffective treatment of deep-seated tumors, adversely affecting patient prognosis. We introduced a cascade nanoreactor that integrates photodynamic therapy (PDT) and chemodynamic therapy (CDT) for comprehensive multimodal OSCC treatment. Utilizing iron oxide nanoparticles and mesoporous silica, we developed the FMMSH drug delivery system, encapsulating the photosensitizer prodrug δ-aminolevulinic acid (δ-ALA). Triphenylphosphine (TPP) modification facilitated mitochondrial targeting, while tumor cell membrane (TCM) coating provided homotypic targeting. The dual-targeting δ-ALA@FMMSH-TPP-TCM nanoparticles demonstrated efficacy in eradicating both superficial and deep tumors through synergistic PDT/CDT. Esterase overexpression in OSCC cells triggered δ-ALA release, and excessive hydrogen peroxide in tumor mitochondria underwent Fenton chemistry for CDT. The synergistic interaction of PDT and CDT mechanisms increased cytotoxic ROS levels, intensifying oxidative stress and enhancing apoptotic and damage mechanisms, ultimately leading to enhanced tumor cell death. PDT/CDT-induced apoptosis generated δ-ALA-containing apoptotic bodies, enhancing anti-tumor efficacy in deep tumor cells. The advantageous anatomical accessibility of oral cancer emphasizes the potential of intratumoral injection for precise and localized treatment delivery, ensuring focused therapeutic agent delivery to maximize efficacy while minimizing systemic side effects. Thus, δ-ALA@FMMSH-TPP-TCM, tailored for intratumoral injection, emerges as a transformative modality in OSCC treatment. This article is protected by copyright. All rights reserved
研究领域:
纳米技术
·
肿瘤学
·
治疗学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Ya-li Xiang,De-yu Tang,Ling-ling Yan,Luo-lin Deng,Xing-han Wang,Xin-yang Liu,Qing-han Zhou
The challenge of drug resistance in bacteria caused by the over use of biotics is increasing during the therapy process, which has attracted great attentions of the clinicians and scientists around the world. Recently, photodynamic therapy (PDT) triggered by photosensitizer (PS) has become a promising treatment method because of its high efficacy, easy operation, and low side effect. Herein, the poly- l -lysine (PLL) modified metal-organic framework (MOF) nanoparticles, ZIF/PLL-CIP/CUR, were synthesized to allow both reactive oxygen species (ROS) responsive drug release and photodynamic effect for synergistic therapy against drug resistant bacterial infections. The PLL was modified on the shell of the zeolite imidazole framework (ZIF) by the ROS-responsive thioketal linker for controllable CIP release. CUR were encapsulated in ZIF as the photosensitizer for blue light mediated photodynamic effect to produce singlet oxygen ( 1 O 2 ) and superoxide anion radical ( O 2 − ) for efficient inhibition towards methicillin-resistant Staphylococcus aureus ( MRSA ). The charge conversion from negative charge (−4.6 mV) to positive charge (2.6 mV) was observed at pH 7.4 and pH 5.5, and 70.9 % CIP was found released at pH 5.5 in the presence of H 2 O 2 , which suggests the good biosafety at physiological pH and ROS-responsive drug release of the as-prepared nanoparticle in the bacterial microenvironment. The as-prepared nanoparticles could effectively kill MRSA and disrupt bacterial biofilm by combination of chemo- and photodynamic therapy. In mice model, the as-prepared nanoparticles exhibited excellent biosafety and synergistic effect with 98.81 % healing rate in treatment of MRSA infection, which is considered as a promising candidate in combating drug resistant bacterial infection.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
微生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Lei Huang,Shihao Zhang,Mengxuan Bian,Xingdong Xiang,Lan Xiao,Jiayi Wang,Shunyi Lu,Weisin Chen,Cheng Zhang,Guokang Mo,Libo Jiang,Yulin Li,Jian Zhang
The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and β-Tricalcium Phosphate (β-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo . Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. Statement of significance Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into β-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro . Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
骨科
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Tian Zhang,Dongsheng Tang,Pengfei Wu,Shaoping Jiang,Yuquan Zhang,Abid Naeem,Yong Li,Chunhui Li,Bo Hu,Shuai Guo,Caixia Sun,Haihua Xiao,Ran Yan,Yuhua Weng,Yuanyu Huang
Immune checkpoint blockade (ICB) therapy is a widely favored anti-tumor treatment, but it shows limited response to non-immunogenic “cold” tumors and suffers from drug resistance. Photodynamic therapy (PDT), as a powerful localized treatment approach, can convert a “cold tumor” into a “hot tumor” by inducing immunogenic cell death (ICD) in tumor cells, thereby enhancing tumor immunogenicity and promoting tumor immunotherapy. However, the effectiveness of PDT is largely hindered by the limited penetration depth into tumor tissues. To address these issues, we proposed an all-in-one drug system with NIR-II photo-accelerated PDT effects, efficient immune checkpoint gene silencing, and a facile manufacturing process. The so-called all-in-one drug system comprises a multi-modal designed polymer PPNP and siRNA. PPNP is an amphipathic polymer that includes the near infrared-II (NIR-II) photosensitizer Aza-boron-dipyrromethene (Aza-BODIPY), a glutathione (GSH)-cleavable linker, and a cationic monomer derived from cholesterol. PPNP can self-assemble and efficiently load siRNA. Under laser irradiation, PPNP triggers a potent ICD cascade, causing the on-demand release of siPD-L1, reshaping the tumor's immunosuppressive microenvironment, effectively inhibiting the growth of various tumors, and stimulating the immune memory. This study represents a generalized platform for PDT and gene silencing, designed to modulate immune-related signaling pathways for improved anticancer therapy.
研究领域:
肿瘤学
·
免疫治疗
·
药理学
·
生物医学工程
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiaoyu Zhao,Chenglong Xue,Yu Liu,Tao Wang,Qi Shuai
The treatment of diabetic wounds remains a challenge due to the interaction between hyperglycemia, immune imbalance and bacterial infection. Herein, we developed a Glu and GSH double-unlocked immunomodulatory nanocascade reactor to accelerate diabetic wounds healing which dynamically manages the wound microenvironment by controlling blood glucose levels, restoring immune regulation and eliminating bacteria. On the one hand, ultra-small gold nanoparticles with GOx activity can catalyse glucose at the diabetic wound site, which can be further enhanced by photothermal effects, thus destroying bacterial biofilm structures, reversing wounds pH, and reducing bacterial reproduction. On the other hand, the sustained controlled release of NO at specific sites was achieved by depleting over-expressed GSH in the wounds to restore normal immune regulation, which not only promotes M2 macrophage polarisation and expressions of anti-inflammatory factors such as IL-10 and TGF-β1, but also produces VEGF and CD31 via the PI3K/AKT signalling pathway. Especially, the chemical resonance energy transfer (CRET) strategy was first applied to diabetic wounds treatment, achieving chemical photodynamic therapy (PDT) while reducing the secondary tissue damage caused by catalytically-generated H 2 O 2 . In summary, the nanocascade reactor provides a new reference for bacterialy-infected diabetic wounds treatment mode by reducing blood glucose and restoring immune regulation in parallel.
研究领域:
纳米技术
·
免疫学
·
伤口愈合
·
糖尿病
·
细菌学
·
生物化学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 17
·1903341
·
IF 15.84
Qing You,Kaiyue Zhang,Jingyi Liu,Changliang Liu,Huayi Wang,Mengting Wang,Siyuan Ye,Houqian Gao,Letian Lv,Chen Wang,Ling Zhu,Yanlian Yang
Multifunctional nanoplatforms for imaging-guided synergistic antitumor treatment are highly desirable in biomedical applications. However, anticancer treatment is largely affected by the pre-existing hypoxic tumor microenvironment (TME), which not only causes the resistance of the tumors to photodynamic therapy (PDT), but also promotes tumorigenesis and tumor progression. Here, a continuous O 2 self-enriched nanoplatform is constructed for multimodal imaging-guided synergistic phototherapy based on octahedral gold nanoshells (GNSs), which are constructed by a more facile and straightforward one-step method using platinum (Pt) nanozyme-decorated metal–organic frameworks (MOF) as the inner template. The Pt-decorated MOF@GNSs (PtMGs) are further functionalized with human serum albumin-chelated gadolinium (HSA-Gd, HGd) and loaded with indocyanine green (ICG) (ICG-PtMGs@HGd) to achieve a synergistic PDT/PTT effect and fluorescence (FL)/multispectral optoacoustic tomography (MSOT)/X-ray computed tomography (CT)/magnetic resonance (MR) imaging. The Pt-decorated nanoplatform endows remarkable catalase-like behavior and facilitates the continuous decomposition of the endogenous H 2 O 2 into O 2 to enhance the PDT effect under hypoxic TME. HSA modification enhances the biocompatibility and tumor-targeting ability of the nanocomposites. This TME-responsive and O 2 self-supplement nanoparticle holds great potential as a multifunctional theranostic nanoplatform for the multimodal imaging-guided synergistic phototherapy of solid tumors.
研究领域:
生物医学工程
·
纳米技术
·
癌症治疗
·
医学成像
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Jun Dai,Xiaoqi Dong,Rui Liu,Biao Chen,Xiyuan Dong,Quan Wang,Jing-Jing Hu,Fan Xia,Xiaoding Lou
Immunotherapy maintains the cancer-immunity cycle via re-activating the immune system, so as to achieve the purpose of anti-tumor. However, the response rate of current tumor immunotherapy strategies is still low. Even the most reported immune checkpoint block (ICB), the objective response rate (ORR) is only about 10–30%. Here, aiming at obtaining a higher response rate, we designed a cascade amplification nanocomposite consisting of the immune adjuvant polyinosinic:polycytidylic acid [Poly (I:C)] and aggregation-induced emission luminogen (AIEgen)-modified modular peptide (named PMRA). The PMRA includes: D PPA-1 peptide (P), an immune checkpoint inhibitor; PLGLAG peptide (M), a matrix metalloproteinase 2 (MMP-2) responsive sequence to promote the release of D PPA-1; RRRRRRRR peptide (R), for loading the Poly (I:C); PyTPA (A), a photosensitizer with AIE property. In cancer-immunity cycle, photodynamic therapy (PDT) mediated by PyTPA promotes the release of tumor-associated antigens (TAAs), and primes T lymphocytes . The cytokines coming from the stimulation of PDT and Poly (I:C) promote the activation of T lymphocytes. The high level of chemokines in tumor microenvironment promotes immune cells migration and infiltration in tumor with the assistance of PDT. Finally, through ICB with D PPA-1 peptide, T lymphocytes enhance the recognition of tumor cells and killing tumor cells. Immunogenic cell death induces the release of more TAAs, which will enter the next cycle and complete the full-loop again. Taking advantages of whole cancer-immunity cycle, the cascade amplification nanocomposite achieved almost 100% ORR in vivo . This concept of whole cancer-immunity cycle enhanced immunotherapy provides a novel perspective for tumor treatment.
研究领域:
癌症生物学
·
免疫学
·
纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES
·
2023
·Vol. 22
·期 4
·905-917
·
IF 3.1
Wen Ying,Zeng Liyun,Chen Qitong,Li Yitong,Fu Mengdie,Wang Zixin,Liu Hong,Li Xiejia,Huang Peng,Wu Wei,Zou Qiongyan,Yi Wenjun
Background The aim of this study was to identify changes in gene expression before and after 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and to investigate the potential mechanism of 5-ALA-PDT based on ribonucleic acid sequencing (RNA-Seq) analysis. Methods Secondary hyperparathyroidism (SHPT) primary cells were isolated from surgically excised specimens and exposed to laser light. The transcription profiles of SHPT primary cells were identified through RNA-Seq. Differentially expressed genes (DEGs) were identified. Enrichment of functions and signaling pathway analysis were performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis were used to validate genes based on RNA-Seq results. Results In total, 1320 DEGs were identified, of which 1019 genes were upregulated and 301 genes were downregulated. GO and KEGG pathway analyses identified significantly enriched pathways in DEGs, including TGF beta in extracellular matrix (ECM), negative regulation of triglyceride biosynthetic process, protein heterodimerization activity, systemic lupus erythematosus, ECM–receptor interaction, focal adhesion and protein digestion and absorption. Protein–protein interaction (PPI) network analyses identified potential heat shock protein (HSP) interactions among the DEGs. Eight HSP genes were also identified that were most likely involved in 5-ALA-PDT, which were further validated by RT-qPCR and western blotting. Conclusions The findings of this descriptive study reveal changes in the transcriptome profile during 5-ALA-PDT, suggesting that gene expression and mutation, signaling pathways, and the molecular network are altered in SHPT primary cells. The above findings provide new insight for further studies on the mechanisms underlying 5-ALA-PDT in SHPT. Graphical abstract
研究领域:
转录组学
·
光动力疗法
·
内分泌学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）