Advanced Science
·
2024
·Vol. 12
·期 4
·2409506
·
IF 14.3
Yunfei Zuo,Pei Li,Wen-Jin Wang,Changhuo Xu,Shuting Xu,Herman H. Y. Sung,Jianwei Sun,Guorui Jin,Weiping Wang,Ryan T. K. Kwok,Jacky W. Y. Lam,Ben Zhong Tang
Precise tumor diagnosis and treatment remain complex challenges. While numerous fluorescent probes have been developed for tumor-specific imaging and therapy, few exhibit effective function in vivo. Herein, a probe called TQ-H 2 is designed that can realize robust theranostic effects both in vitro and in vivo. In vitro, TQ-H 2 specifically targets the lysosome and reacts with hydroxyl radical (·OH) to generate TQ-HA, which lights up the cells. TQ-HA generates reactive oxygen species (ROS) under light irradiation, enabling the simultaneous induction and monitoring of apoptosis and ferroptosis in tumor cells. Remarkably, TQ-HA also acts as a self-amplifier, autocatalytically activating TQ-H 2 by generating ·OH under light exposure. This self-amplification aligns with the tumor microenvironment, where TQ-H 2 undergoes chemical transformation, distinguishing tumors from healthy tissue via near-infrared (NIR) fluorescence imaging. Furthermore, ROS generated by TQ-HA effectively kills tumor cells and inhibits tumor growth without harming normal cells. This study offers a promising strategy for targeted tumor theranostics using self-amplifying microenvironment-responsive fluorescent probes.
研究领域:
生物医学
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分子影像学
·
癌症治疗
✓ 已验证
DOI
高影响因子
ACS Nano
·
2025
·
IF 16
Min Jian,Xuan Ding,Qi Li,Yongye Zhao,Bo Wang,Lijun Yang,Lei Jiang,Jun Gao
Proton channels have both high permeability and selectivity, a property that remains unparalleled by artificial materials yet is highly demanded in many applications, including acid recovery and power generation. This work takes inspiration from the structure and surface chemistry of biological proton channels and presents a method to construct covalent organic framework (COF) membranes consisting of high-performance artificial proton channels. The membrane was purposefully rendered amorphous, which eliminates most of the nanoscale pores and induces high steric hindrance to ions. On the other hand, the channels were functionalized with hydrogen-donating groups, allowing protons to hop fast. Interestingly, we found that the presence of hydrated protons causes additional hindrance to ions and thus self-amplifies the proton selectivity. Consequently, the proton selectivity against toxic heavy metal ions is up to 104, significantly surpassing that of commercial acid-recovery membranes. The permeability is comparable to that of biological proton channels (a few mol m–2 h–1). Such membranes allow us to recycle acid from industrial waste brines by a simple diffusion dialysis process without the risk of toxic ion leakage. At the same time, the entropy released by the proton diffusion can be harvested to generate power, achieving a power density superior to that of most previously reported membranes for osmotic energy harvesting.
研究领域:
材料科学
·
环境工程
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Qiuli Wang,Jiahao Meng,Lingling Huang,Feng Wu,Xue Yi,Guanghao Su,Ying Li,Zhenqing Hou,Zhongxiong Fan
How to efficiently synthesize toxic chemo-drugs in the hypoxia tumor microenvironment still faces a huge challenge. Herein, we have tailored engineered vehicle-free nanoreactors by coordination-driven co-assembly of photosensitizer indocyanine green (ICG), transition metal platinum (Pt), and nontoxic 1,5-dihydroxynaphthalene (DHN) to self-amplify O2 and cascade chemo-drug synthesis in tumor cells for self-reinforcing hypoxic oncotherapy. Once vehicle-free nanoreactors are internalized into tumor cells, they show a serious instability that results in rapid disassembly and on-demand drug release under the stimuli of acidic lysosome and laser radiation. Notably, the released Pt can efficiently decompose the endogenous hydrogen peroxide (H2O2) into O2 to alleviate tumor hypoxia, which is conducive to enhancing the photodynamic therapy (PDT) efficiency of the released ICG. Complementarily, a large amount of the 1O2 generated by PDT can efficiently oxidize the released nontoxic DHN into the highly toxic chemo-drug juglone. Therefore, such vehicle-free nanoreactors can achieve intracellular on-demand cascade chemo-drug synthesis and self-reinforce photo-chemotherapeutic efficacy on the hypoxic tumor. On the whole, such a simple, flexible, efficient, and nontoxic therapeutic strategy will broaden the study of on-demand chemo-drug synthesis and hypoxic oncotherapy.
研究领域:
癌症治疗
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纳米医学
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生物化学
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Xiaoxuan Ren,Xuwen Gao,Guizheng Zou
Optical single molecule detection is normally achieved via amplifying the total emission of photons of luminophores and is strongly anticipated to extend the commercialized application of chemiluminescence (CL). To overcome the limited CL photons of molecule luminophores, herein, a nanocrystal (NC) luminophore self-amplified strategy is proposed to repetitively excite CL luminophores for amplifying the total CL photons per luminophore, which can be exploited to perform CL immunoassays (CLIAs) toward single molecule detection via employing KMnO4 as the CL triggering agent and the dual-stabilizer-capped CdTe NCs as the CL luminophore. KMnO4 can oxidize the S element from each stabilizer of mercaptopropionic acid (MPA) and release enough energy to excite the CdTe core for flash CL. The substantial MPA around each CdTe core enables every CdTe luminophore to be repetitively excited and give off amplified total CL photons in a self-enhanced way. The CL of CdTe NCs/KMnO4 can release all photons rapidly, and the collection of all these photons can be utilized to determine the model analyte of thyroid-stimulating hormone antigen (TSH) with a limit of detection of 5 ag/mL (S/N = 3), which is corresponding to about 2–4 TSH molecules in a 20 μL sample. The whole immunologic operating process can be terminated within 6 min. This strategy of repetitively breaking the CL reaction involving chemical bonds within one luminophore is promising for semi-automatic as well as fully automatic single molecule detection and extends the commercialized application of CL immunodiagnosis.
研究领域:
分析化学
·
生物技术
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纳米技术
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Minghui Hu,Yingyu Zhang,Jie Zhang,Xianwei Zhang,Mengxin Zhang,Kangbo Liu,Lifeng Li,Zhidan Yu,Fei Zhang,Wancun Zhang
In vivo optical tumor molecular imaging encounters significant challenges in achieving adequate tumor specificity and sensitivity, largely attributed to off-tumor signal leakage and the relatively low expression levels of target molecules. Therefore, a double self-amplified programmable allosteric DNA nanomachine (named HPs-tFNA) is developed through two elaborately designed hairpin structures (HP1 and HP2) hybridized on tetrahedral framework DNA (tFNA), enabling rapid, specific, and sensitive tumor molecular imaging using the highly specific expression of apurinic/apyrimidinic endonuclease 1 (APE1) in the tumor cytoplasm as a stimulus-response target. In the presence of APE1, HP2 modifies two apurinic/apyrimidinic sites (AP sites), which can be specifically recognized and cleaved by APE1, releasing a significant number of cyclic sequences (cyclic-seq) and achieving initial APE1-assisted signal amplification. Subsequently, cyclic-seq hybridizes with HP1, inducing a conformational change that converts the stem-loop structure of HP1 to a linear form. This structural change facilitates the spatial separation of the fluorophore and quencher, thereby generating fluorescence signals. Furthermore, APE1 incises two AP sites within the HP1 loop region, resulting in the release of cyclic-seq. The released cyclic-seq can hybridize with additional HP1 to continuously amplify the fluorescence signal in a cyclic manner, thereby achieving the second round of signal amplification assisted by APE1. The experimental results of this study demonstrated that HPs-tFNA can achieve rapid in situ tumor molecular imaging and guide precise surgical excision in vivo, with superior spatial specificity. In particular, HPs-tFNA can effectively monitor drug resistance in neuroblastoma cells and stratify risk levels of neuroblastoma via plasma analysis.
研究领域:
生物医学工程
·
分子影像学
·
纳米医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Yinjia Cheng,Qin Mo,Fangyu Zeng,Yuqing Wang,Muhai Liu,Yuting Li,Qiangyu Liu,Siyong Qin,Wenlong Liu,Yihan Ma,Aiqing Zhang
Conventional chemotherapy for hepatocellular carcinoma (HCC) often suffers from nonspecific delivery and consequent off-target toxicity, resulting in diminished efficacy. The rational design of theranostic nanoplatforms, which integrate biomedical imaging with therapeutic functions, can circumvent the intrinsic limitations of conventional chemotherapeutic agents. This approach enhances the efficacy of synergistic chemotherapy-based cancer treatments and advances the development of personalized medicine. Herein, we report the facile construction of a versatile theranostic nanoplatform (D@LADFe) for tumor-specific magnetic resonance (MR) imaging and synergistic chemo/chemodynamic/ferroptotic therapy. The nanoplatform D@LADFe was formed by encapsulating doxorubicin (DOX) and coordinating iron (Fe 3+ ) into chimeric peptide (LAD) nanoparticles. The LAD nanoparticles comprise the therapeutic peptide KLAK-YSV, a dopamine-derived DOPA moiety, and hydrophobic linoleic acid (LA). Upon uptake by cancer cells, D@LADFe nanoparticles undergo gradual decomposition, facilitating the on-demand release of DOX and Fe 3+ ions. Intracellular Fe 3+ ions function as endogenous contrast agents, enabling tumor-specific MR imaging. Concomitantly, the high concentration of glutathione (GSH) reduces Fe 3+ to Fe 2+ , which then catalyze the conversion of hydrogen peroxide (H 2 O 2 ) into cytotoxic hydroxyl radicals (•OH) via the Fenton reaction. This reaction not only drives chemodynamic therapy (CDT) but also initiates a cascade of downstream effects, including glutathione (GSH) depletion, membrane lipid peroxidation (LPO) and cancer cell ferroptosis. Subsequent LPO targets the unsaturated double bonds in the LA moiety of LAD, amplifying the in situ production of toxic singlet oxygen ( 1 O 2 ) via the Russell mechanism, facilitated by the self-amplified nanoreactor (LA( OOH )D) and Fe 2+ . These D@LADFe nanoparticles exhibited excellent Fenton-reaction efficiency with a Michaelis-Menten constant (K m ) and maximum velocity (V max ) of 11.5 × 10 −3 M and 7.8 × 10 −8 M s −1 , respectively. Furthermore, DOX selectively accumulates in tumor tissues and induces cellular apoptosis by interfering with DNA replication, downregulating adenosine triphosphate (ATP) production, and upregulating mitochondrial reactive oxygen species (ROS). This cascade ultimately elevates cellular ROS levels, triggering ferroptosis. In vitro assays demonstrated that D@LADFe treatment significantly increased Hepa1–6 cell apoptosis to 87 %, exceeding the apoptotic rates in the single-treatment groups and the control groups. Finally, in vivo studies substantiated that intravenously administered D@LADFe nanoparticles significantly inhibited tumor growth suppression versus monotherapies (CT, CDT, or ferroptosis alone), ascribing to their multimodal mechanism. Given its favorable biocompatibility and biosafety, this work proposes a rational design strategy to employ a novel self-assembling peptide-based nanoplatform for tumor-specific MR imaging and multimodal therapeutic applications.
研究领域:
肿瘤学
·
纳米医学
·
分子影像学
·
转化医学
·
药剂学
·
生物材料
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Qingyu Zong,Jisi Li,Xuan Xiao,Xiaojiao Du,Youyong Yuan
The selective activation of stimuli-responsive polymers in the tumor microenvironment is a great concern to achieve intelligent cancer therapy, but most of them show inadequate response due to insufficient endogenous triggering agents. Herein, we rationally designed a reactive oxygen species (ROS)-responsive cinnamaldehyde (CA)-based poly(thioacetal), consisting of ROS-responsive thioacetal (TA) and ROS-generating agent CA, with self-amplified chain-shattering polymer degradation . The mechanism of self-amplified chain-shattering is that endogenous ROS as a triggering agent facilitates chain cleavage of TA with the release of CA, which in turn produces more ROS through mitochondrial dysfunction, resulting in an exponential polymer degradation cascade. The polymer can be further modified with anticancer drug doxorubicin (DOX) for cooperative amplification of oxidative stress and immunogenic cell death (ICD) of tumor cells, thereby boosting the effect of chemo-immunotherapy. The self-amplified chain-shattering polymer designed in this work holds great promise in developing stimuli-responsive polymers for efficient drug delivery. Statement of significance This study presented an approach to utilize self-amplified chain-shattering cinnamaldehyde-based poly (thioacetal) as a drug delivery system to restrain tumor growth and boost chemo-immunotherapy. The endogenous ROS as a triggering agent initiates the chain cleavage with the release of CA, which in turn produces ROS through mitochondria dysfunction, resulting in an exponential polymer degradation cascade and rapid drug release.
研究领域:
癌症治疗
·
高分子科学
·
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
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yingwen Lu,Pengfei Shan,Weilin Lu,Xiangping Yin,Haiwei Liu,Xiaoyue Lian,Jiayi Jin,Yuxi Qi,Zhongyu Li,Zhihui Li
Bacterial infection is a serious global health threat, and the clinical abuse of antibiotics has severe systemic toxicity and leads to multidrug-resistant bacteria. Stimuli-responsive polymers represent an encouraging strategy for intelligent treatment; however, inadequate polymer degradation and drug release are still challenging, especially in bacterial infection, where exponential rates of degradation and release are urgently needed. Here, we reported a facile 1,1,3,3-tetramethylguanidine (TMG)-promoted polyesterification method for the preparation of a novel antibiotic-free, PEGylated ROS-responsive polymeric prodrug of cinnamaldehyde (PRPCA), and demonstrated its remarkable intrinsic antibacterial activities and the acceleration of infected wound healing for the first time. The CA was covalently incorporated into the backbone of the polyester by a ROS-responsive thioacetal linkage and can be triggered to release by the ROS generated during bacterial growth. The released CA successively induced more ROS generation and the polymer achieved self-accelerating degradation via the positive feedback. The PRPCA-based nanomedicine possessed great bactericidal effects against both S. aureus and E. coli in vitro . Strikingly, the self-amplifying degradation of PRPCA nanoparticles caused abrupt “self-destruction” of S. aureus . More importantly, PRPCA significantly accelerated the S. aureus -infected wound healing process without systematic toxicity. Collectively, this work opens an avenue to develop novel self-amplifying stimuli-responsive polymers based on natural antimicrobial for superior wound disinfection and healing.
研究领域:
药学
·
材料科学
·
生物医学工程
·
纳米技术
·
传染病学
✓ 已验证
产品关联
DOI
高影响因子
Science China-Chemistry
·
2024
·
IF 10.4
Yang Shuguang,Hu Lijun,Xiao Hong,Xiao Zecong,Shuai Xintao
Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy. Nonetheless, the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes. Herein, we reported a self-amplifying fluorescent molecular probe, Bis-HTP-ICG, for photodynamic therapy (PDT) and subsequent PDT-induced immunoreaction. The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase (MPO), a crucial enzyme secreted by neutrophils at inflammation sites. Upon exposure to laser irradiation, Bis-HTP-ICG showed a high PDT efficacy, inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion. The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis, instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG, neutrophils and MPO. Meanwhile, PDT efficiently incites immunogenic cell death (ICD) in tumor cells, initiating an anti-tumor immune response including dendritic cells (DCs) maturation, T cell proliferation and reprogramming of tumor-associated neutrophils (TANs). This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels, potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.
研究领域:
癌症治疗
·
免疫学
·
药理学
·
分子生物学
✓ 已验证
DOI
高影响因子
Small
·
2025
·
IF 12.1
Xianquan Feng,Yan Zhang,Wanjing Lin,Jing Li,Fei Wu,Qingyu Lu,Hongtao Song,Hao Zhang,Fenghua Lan,Jun Lu
The efficacy of immunotherapy in triple-negative breast cancer (TNBC) is significantly hindered by its low immunogenicity and immunosuppressive tumor microenvironment. Non-invasive photodynamic therapy (PDT) is increasingly recognized as a potential immunotherapeutic stimulant in the treatment of TNBC. However, photodynamic immunotherapy is constrained by tumor hypoxia and excessive inflammation suppression during the course of treatment. Herein, a simple and efficacious biomedicine is formulated to overcome adverse influences by amplifying photodynamic immunotherapy, thereby stimulating the systemic immune response. Specifically, the approach targeted tumor delivery by employing specific agents such as the photosensitizer (verteporfin), the hypoxic ameliorator (atovaquone), and the cyclooxygenase-2/prostaglandin E2 (COX-2/PGE2) signaling blocker (celecoxib). More importantly, the biomedicine effectively ameliorated hypoxia and inhibited COX-2/PGE2 signaling, thereby amplifying PDT-induced immunogenic cell death. This, in turn, enhanced the efficacy of photodynamic immunotherapy and triggered a robust immune response cascade. Notably, the self-amplifying photodynamic biomedicine significantly inhibited primary tumors, distal tumors, lung metastases, and post-operative recurrence while maintaining high biocompatibility. To sum up, the work provides a viable cascade stimulation approach and an efficient biomedical nanoplatform, offering a novel strategy for photodynamic immunotherapy of TNBC in the clinic.
研究领域:
肿瘤学
·
免疫学
·
药理学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2022
·
IF 9.965
Yupeng Guan,Chengyuan Xing,Tongyu Tong,Xinyi Zhang,Jun Li,Huikun Chen,Junfeng Zhu,Yang Kang,Jun Pang
Conventional chemotherapy efficacy is impeded by poor water solubility, inferior tissue targeting, and severe systemic toxic effect. Synergistic chemotherapy has become prominent with the stimulus–response drug delivery system (DDS) to treat solid malignancies. The most popularly employed responsive stimulus is reactive oxygen species (ROS), which is proven to primarily sensitize chemotherapy and enhance antitumor impact. In this study, we have successfully developed smart dual responsive nanocarriers with ROS self-amplification, particularly responding to disassemble under the high levels of ROS and esterase in the tumor microenvironment (TME) and to release docetaxel (DTX) efficiently. Additionally, we utilized palmitoyl ascorbate (PA) as a stabilizer by taking advantage of its amphiphilic structure. PA is also an excellent ROS generator that produces a large amount of hydrogen peroxide (H 2 O 2 ) in TME to achieve ROS self-amplification. Also, elevated levels of ROS could continue to activate ROS-sensitive thioketal and make the remaining nanocarriers disassemble for sustaining the release of chemotherapeutics, realizing a positive feedback loop for ROS generation and ROS amplification, as well as sensitizing chemotherapy efficacy. The smart dual responsive nanocarriers may serve as a promising and prospective strategy for treating prostate cancer and promoting synergistic cancer therapy.
研究领域:
纳米技术
·
癌症治疗
·
药学科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Jiali Deng,Yi Zhu,Jingyi Wang,Xinyi Ding,Sunxian Dai,Jiajing Guo,An Chen,Rong Cao,Li Zhang,Haiyu Liu,Xiance Zhao,Xinyang Wu,Hongwei Lu,Zhongling Wang
The accurate non-invasive monitoring of pyroptosis-based immunotherapy is hindered by the lack of sensitive imaging strategies. Here, a self-amplifying chemical exchange saturation transfer (CEST) imaging-guided pyroptosis therapy (pyropCEST) strategy for activating and highly sensitive visualizing pyroptosis-induced immune response is reported. The biocompatible nanoplatform, composed of human serum albumin loaded with gemcitabine, can induce pyroptosis in the tumor microenvironment, promoting dendritic cell maturation and T cell activation. Meanwhile, nanoprobe dissociation enhances chemical exchange between the NH 2 groups within gemcitabine/albumin and bulk water, yielding self-amplified CEST signals and boosting imaging sensitivity to 435% compared to normal physiological conditions. In the subcutaneous tumor mouse model, the long-term accumulation of nanoprobes in the tumor leads to a 2.5-fold increase in CEST signal over free gemcitabine. Changes in CEST signal serve as an indicator for evaluating CD8 + T cell infiltration and tumor growth, exhibiting an excellent “theranostic correlation.” Moreover, integration with multiparametric MRI enables comprehensive tracking of therapeutic outcomes, including suppression of distant metastases. Collectively, this pyropCEST strategy introduces a clinically translatable imaging paradigm for non-invasive, dynamic visualization of pyroptosis and immune microenvironment remodeling.
研究领域:
肿瘤学
·
分子影像学
·
免疫治疗
·
纳米医学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）