JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2021
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IF 8.128
Ke Ma,Jingtao Shi,Yuxin Pei,Zhichao Pei
Most carrier-based nano drug delivery systems (nano-DDSs) are subjected to complex preparation or purification processes, metabolic instability and potential systemic toxicity. To overcome these issues, it is urgent to develop a multifunctional carrier-free nano-DDS that can be fabricated by a simple approach for enhanced anticancer efficacy. In this work, the carrier-free supramolecular nanoprodrug (CF SNPD) based on lactose (Lac) functionalized dimeric camptothecin (CPT) was developed, in which Lac and CPT were conjugated by the aromatized thioacetal (ATA, a reactive oxygen species (ROS)-responsive bond). The obtained Lac-ATA-CPT 2 prodrug and the photosensitizer Chlorin e6 (Ce6) formed CF SNPD (denoted as [email protected] 2 NPs) in water by supramolecular self-assembly. The design of dimeric CPT endowed [email protected] 2 NPs with ultrahigh drug-loading capacity (up to 94%) and excellent stability. The Lac-functionalized CF SNPD displayed active specific targetability to HepG2 cells resulting from the carbohydrate-protein interactions. Furthermore, the fluorescence signal of Ce6 facilitated the precise tracking and localization of [email protected] 2 NPs within the cell. Meanwhile, the ROS generated by Ce6 not only cleaved ATA linker to trigger on-demand CPT release, but also exhibited a killing effect on tumor cells, enabling synergistic therapy via CPT-mediated chemotherapy (CT) and Ce6-induced photodynamic therapy (PDT). Therefore, the multifunctional CF SNPD may be one of the promising therapeutic options for liver cancer.
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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分子生物学
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International Journal of Nanomedicine
·
2025
·
IF 6.5
Binrui Shi,Mingjie Li,Renjie Feng,Guihua Wang,Liyong Deng,Yueyong Li,Kezhen Wang,Meng Du,Zhiyi Chen
Purpose: Melanoma, a highly aggressive superficial malignancy with rising incidence and mortality, faces limited sonodynamic therapy (SDT) efficacy due to poor sonosensitizer accumulation and penetration. To overcome this, we employed chlorin e6 (Ce6), a high-ROS-yield sonosensitizer, and enhanced its tumor delivery using a synergistic microneedle (MN) and ultrasound (US) strategy.Methods: Using melanoma as an application scenario, a “stepwise drug delivery” system was developed. It consisted of dissolving MN encapsulating US-responsive nanoparticles (Ce6-PFP@PLGA, CPP) and termed CPP@MN. CPP@MN breaks through the stratum corneum to deliver CPP to tumors, followed by US-triggered cavitation that mediates perfluoropentane (PFP) phase transition to enhance the tumor-penetrating capability of chlorin e6 (Ce6). Delivery efficacy was validated using three experimental models: an in vitro agarose skin phantom, ex vivo pig skin, and in vivo tumors. Furthermore, the anti-tumor efficacy of US-combined CPP@MN was evaluated at the cellular level and in tumor-bearing mice.Results: According to the results, CPP@MN showed excellent transdermal performance, including rapid dissolution of sonosensitizer and sufficient mechanical strength. MN combined with US increased the tumor penetration depth of loading drug by 2.5– 4 times across all experimental models. Ultrasonic cavitation promotes nanoparticle-derived Ce6 release and deeper tumor diffusion, resulting in specific anti-tumor efficacy.Conclusion: This innovative “stepwise drug delivery” system addresses persistent challenges in superficial tumor SDT, including inadequate sonosensitizer aggregation and poor tissue penetration, while establishing a multifunctional platform for spatiotemporally controlled drug release that sequentially overcomes the skin biological barriers.
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JOURNAL OF COLLOID AND INTERFACE SCIENCE
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2026
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IF 9.6
Yingchao Li,Feiyan Zhao,Chuanxiu Zhu,Chunyan Wu,Weilin Wang,Yu Zhang,Qiaoying Hu,Jiayao Wen,Guangxi Zhai,Zhijing He,Jingchao Liu,Xiaoye Yang
While ferroptotic therapy has emerged as a promising strategy for triple-negative breast cancer (TNBC), cellular ferroptosis resistance poses a significant challenge. Given the compensatory up-regulation of dihydroorotate dehydrogenase (DHODH) following glutathione peroxidase 4 (GPX4, the primary ferroptosis defender) inhibition, concurrent GPX4/DHODH suppression has been recently revealed essential for ferroptosis sensitization. However, DHODH, as a pivotal nucleotide metabolism enzyme, might exert complex even contradictory effects on tumor ferroptotic therapy, which are poorly understood. This work reveals for the first time that brequinar (BQR, a DHODH inhibitor) exerts dual-edged effects on ferroptotic therapy against 4 T1 cells: besides its well-known disruption of cellular redox balance for ferroptosis sensitization, BQR-intervened pyrimidine metabolism blocks tumor growth, accompanied by up-regulation of lipid droplets (LDs), which paradoxically aggravates ferroptosis resistance. To address this dilemma, we pioneer the combination of DGAT1 inhibition for lipid metabolism remodeling. As a proof-of-concept, we fabricate a BQR/A922500 (a DGAT1 inhibitor) co -encapsulated metal-polyphenol network (named AB@HA-TA/Fe) by one-pot method for robust targeted ferroptotic therapy of TNBC. AB@HA-TA/Fe triggers cellular ferroptosis by boosting iron level and dual DHODH/GPX4 suppression; and the combination of A922500 rescues BQR-induced LD up-regulation, reversing ferroptosis resistance. The biosafety and ferroptotic therapy efficacy of AB@HA-TA/Fe are verified both in vitro and in vivo . This work helps to accelerate DHODH inhibitors' clinical translation by elucidating previously overlooked mechanisms limiting DHODH inhibitors' efficacy and proposing synchronous DGAT1 inhibition as a countermeasure. The fabricated nanoweapon AB@HA-TA/Fe presents a novel dual metabolic intervention paradigm for ferroptosis sensitization, proposing an innovative framework for ferroptosis-integrated combination therapy of TNBC.
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CHEMICAL ENGINEERING JOURNAL
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2026
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IF 13.2
Ruo-Yun Zhang,Wei Yue,Yang Xuan,Long Qi,Lin-Lin Guo,Zhen-Zhen Zhu,Ming Yang,Zhang-Jie Pu,Guo-Qiang Li,Xin-Yi Mao,Ding Zhou,Zhao-Wei Zhang
Immunogenic cell death (ICD) attracts significant attention by initiating adaptive immune responses for antitumor immunotherapy. Although ROS is developed to trigger ICD as an inducer, the effect of immunotherapy is compromised by the scavenging of ROS in the immunosuppressive tumor microenvironment. Herein, we report an injectable cascade-amplified ICD nanofiber hydrogel self-assembled from steroid drug prednisolone sodium phosphate (PSP) and calcium chloride for the local delivery of glutaminase inhibitor CB-839 and the sonosensitizer Ce6 (CCPG). ROS is generated by stimulating Ce6 under ultrasound (US), which disrupts the Ca 2+ buffer capacity of mitochondria to induce Ca 2+ influx, thereby triggering ICD to release damage-associated molecular patterns (DAMPs) from dying tumor cells for initiating T cell infiltration. Moreover, ICD induction is further amplified by the glutaminase inhibitor CB-839. CB-839 suppresses glutathione (GSH) synthesis by inhibiting the conversion of glutamine to glutamate as the precursor of GSH, thereby limiting the scavenging of Ce6-generated ROS and enhancing their antitumor and ICD-triggering effects. Additionally, anti-inflammatory PSP suppresses matrix metalloproteinase-2 (MMP-2) expression, resulting in facilitating T cell infiltration. As a consequence, this work highlights a strategy to reprogram immunosuppressive tumor microenvironment via cascade-amplified ICD by inhibiting the scavenging of ROS to maintain Ca 2+ overload, providing new insights for enhancing the efficacy of immunotherapy.
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JOURNAL OF NANOBIOTECHNOLOGY
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2026
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IF 15
Wang Teng,Wang Yu,Wang Bingjie,Su Yanguo,Jiang Tianze,Xu Wenhua,Zhao Xia,Tao Jiaojiao,Shi Chenshuai,Xu Xiang,Xu Jinlong
Cancer metastasis is a serious threat to human health. Cancer stem cells (CSC) are closely related to tumor metastasis, but it is difficult to achieve accurate drug delivery and effective inhibition of CSC due to the complex tumor microenvironment. Herein, we report a living cell delivery system, C-H@M2, engineered by loading M2 macrophages with carrier-free Ce6/Honokiol self-assembled nanoparticles. This system is designed to harness the tumor’s intrinsic recruitment mechanism for targeted anti-metastasis therapy. Acting as a “Trojan Horse”, C-H@M2 exploits the active recruitment of M2 macrophages by CSC to achieve precise tumor homing. Upon laser irradiation, the macrophages undergo photo-triggered immunogenic lysis (“self-explosion”), leading to the burst release of therapeutic payloads and the induction of robust immunogenic cell death (ICD). HK as an inhibitor of Forkhead box M1 (FOXM1) inhibits CSC stemness and epithelial mesenchymal transition (EMT) in tumor tissues. In vivo experimental results demonstrate that C-H@M2 significantly inhibits tumor and lung metastasis through a triple-modal strategy: Self-explosion enhanced ICD effect, stemness and EMT inhibition, CSC killing by stemness inhibition and PDT. Our study provides a novel strategy for CSC targeted therapy and cancer metastasis inhibition. Graphical
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ACS Applied Nano Materials
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2026
·Vol. 9
·期 30
·14209-14222
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IF 5.8
Li Hui,Fan Jingnan,Liao Jiamei,Chen Ke,Tang Qingxia,Tang Hua,Wang Dan
Hepatocellular
carcinoma (HCC) remains a significant therapeutic
challenge due to multiple bottlenecks, including low early diagnosis
rates, rapid disease progression, and limited efficacy of monotherapy.
Against this backdrop, multimodal integrated treatment has emerged
as a core solution. Here, we reported a tumor-microenvironment (TME)-activatable
“nano-cocktail” (UMDCAc) that synchronizes photodynamic
(PDT), chemodynamic (CDT), and starvation (ST) therapies for synergistic
HCC eradication. UMDCAc was engineered by growing hollow MnO 2 (HMnO 2 ) on upconversion nanoparticles (UCNPs), coloading
dihydroartemisinin (DHA) and the photosensitizer chlorin e6 (Ce6),
and in situ anchoring ultrasmall gold nanoparticles (AuNPs) that mimic
glucose oxidase (GOx). Surface modification with cyclic RGD peptides
enabled active targeting of α v β 3 integrin. The targeting strategy synergizes with near-infrared (NIR)
light-activated catalysis to enhance therapeutic efficacy. In vitro and in vivo data demonstrate that UMDCAc achieves tumor suppression
through synergistically amplified reactive oxygen species (ROS) generation,
hypoxia relief, and targeted delivery, while maintaining favorable
biocompatibility and safety and exhibiting superior efficacy over
monotherapy. The synergistically generated ROS compromise cellular
antioxidant defenses, induce lipid peroxidation, and double the apoptosis
rate, thereby producing effective antitumor effects. Therefore, this
innovative multimodal strategy offers opportunities for collaborative
cancer therapy.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Siyu Tong,Shuang Zuo,Guodong Liu,Shiping Wang,Yu Chen,Ping He,Shan Liu
GSH-responsive HPCT enable CT/SDT synergistic therapy. • HPCT induces both ferroptosis and apoptosis. • HPCT actively target CD44-overexpressing tumor cells. • Dual death pathways overcome single-treatment limitations for enhanced efficacy. Cancer is one of the leading causes of death worldwide. Chemotherapy (CT) is one of the main clinical treatment modalities; however, it has limitations as a single treatment approach. To achieve a multi-modal synergistic therapy, this study designed and synthesized two amphiphilic molecules, PEG-SS-CPT and HA-SS-Ce6, and subsequently constructed intelligent nanoparticles HPCT through self-assembly, which possess both active targeting and glutathione (GSH) responsiveness for CT and sonodynamic therapy (SDT). This system employs hyaluronic acid (HA) to specifically target tumor cells that exhibit elevated CD44 expression. It responds to the high levels of GSH present in the tumor microenvironment, allowing for the release of CT drug camptothecin (CPT), while also producing singlet oxygen through Ce6 activation under ultrasound (US) stimulation, thereby simultaneously inducing apoptosis and ferroptosis in tumor cells. In the CT26 colon cancer-bearing mouse model, HPCT combined with US demonstrated a significant synergistic anti-tumor effect, with a tumor growth inhibition rate of 80.4 ± 3.1%, and did not cause significant systemic toxicity. This study indicates that through the rational design of intelligent nanoparticles integrating CT and SDT, it is possible to effectively overcome the limitations of single treatment modalities, providing a new strategy to enhance cancer treatment efficacy.
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Advanced Healthcare Materials
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2026
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IF 11
Jinling Zheng,Yingying Ke,Dandan Meng,Marie Helene Delville,Shiwen Yu,Yiteng Huang,Xiaoyu Xu,Xu Zhang,Shayibai Shabiti,Na Liang,Yujue Wang,Fangjie Li,Hongfei Chen,Wenjun Li
Sono-photodynamic therapy (SPDT) offers a non-invasive, spatiotemporally precise approach to cancer treatment, but its effectiveness is still limited by poor tumor specificity and penetration. To address this, we developed a cascade-targeted type I/II sensitizer, Ce6-TPP-Phe-Tyr (CTPT), which integrates chlorin e6 (Ce6), triphenylphosphonium (TPP), and a phospho-peptide motif for precise tumor targeting and potent SPDT. Upon dephosphorylation by tumor-overexpressed alkaline phosphatase (ALP), CTPT undergoes enzyme-instructed self-assembly (EISA) into nanoparticles (CTPT NPs), promoting their accumulation and retention in tumors. The TPP cations then guide these nanoparticles to mitochondria, concentrating the therapeutic payload at this critical organelle for cellular energy metabolism. Subsequent ultrasound/laser irradiation further enhances tissue permeability and triggers the generation of both type I and type II reactive oxygen species (ROS), leading to potent oxidative damage. This integrated strategy of EISA and mitochondria-targeted SPDT achieved approximately 86% tumor regression in ALP-overexpressing xenografts. This strategy minimizes systemic toxicity and achieves potent tumor regression by cascade delivery of the therapeutic agent, thereby significantly enhancing the precision and efficacy of SPDT.
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ACS Applied Nano Materials
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2026
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IF 5.8
Shoulong Wang,Fengmeng Teng,Fengmin Wu,Changlong Li,Hui Zhang,Chunbing Zhang,Dong Zhang
In recent years, the abuse of antibiotics has led to the emergence of numerous drug-resistant bacteria. Given that single antimicrobial materials can hardly achieve satisfactory inhibition against pathogenic bacteria, it is urgent to develop composite antimicrobial materials and strategies. In this work, inorganic piezoelectric ZnO nanoparticles were used as the core, modified to improve hydrophilicity, coated with polyethylene glycol (PEG), and then conjugated with the sonosensitizer chlorin e6 (Ce6) via amide bonds to form ZnO@PEG@Ce6 (ZGC) nanocomposites. The nanocomposites were characterized by Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), cavitation intensity, absorbance, band gap, zeta potential, and particle size analysis. ZGC exhibits an octahedral structure with a uniform particle size distribution, and FTIR verified the stable chemical linkage among components. Synergy between ZnO piezoelectricity and Ce6 sonosensitivity greatly enhances ROS generation and results in superior sonodynamic antimicrobial activity. Gram-negative bacterium Pseudomonas aeruginosa, Gram-positive bacterium Staphylococcus aureus, and Candida albicans were selected as experimental subjects to study the antimicrobial activity and mechanism of the composite material ZGC. The experiment showed that under the action of ultrasound, the inhibition rates of ZGC against P. aeruginosa, S. aureus, and C. albicans were 58.7%, 68.29%, and 94.55%, respectively, which overcomes the disadvantage of the narrow antimicrobial spectrum of traditional sonosensitizers. Scanning Electron Microscope (SEM) images revealed that the synergistic effect of ZGC and ultrasound destroyed the surface structure of pathogenic strains, allowing reactive oxygen species to penetrate and damage the pathogens. ZGC-mediated sonodynamic therapy shows promising applications in chronic infected wound healing and implant-related infections, enabling efficient elimination of drug-resistant bacteria and precise antimicrobial treatment. This study provides insights and theoretical support for the development of broad-spectrum and highly efficient sonodynamic antimicrobial therapy.
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Nature Communications
·
2026
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IF 18.1
Topatana Win,Sun Yuchao,Xie Tianao,Zhu Yiyuan,Yang Taorui,Shen Ruijing,Ran Peng,Li Chengao,Chen Jiadong,Shen Xuqiu,Lu Ziyi,Han Yina,Shan Yukai,Li Shijie,Chen Tianen,Cai Xiujun,Deng Renren,Juengpanich Sarun,Chen Mingyu
Persistent luminescence is a promising approach for photodynamic therapy (PDT) in deep-seated tumors, as it provides sustained light within tissues, eliminating the need for continuous external illumination. However, the uncontrollability of light within the body complicates precise spatiotemporal regulation. In this study, we report X-ray preactivated elimusertib-loaded tumor-targeted photodynamic nanoparticles (ETPNs), featuring reversible “on-off” afterglow properties. The excellent afterglow properties of X-ray-activated porous NaYF 4 :Er@NaGdF 4 persistent luminescence nanoparticles enable the continuous activation of chlorin e6 (Ce6) to generate reactive oxygen species (ROS), leading to DNA damage. The integration of elimusertib potentiates ROS-induced DNA damage and activates the cGAS-STING pathway, thereby enhancing immuno-photodynamic therapeutic efficacy. All in vivo experiments were conducted using female mice. Our findings highlight the potential of ETPNs to advance the therapeutic landscape for deep-seated tumors, offering a robust and controllable platform for combined immuno-photodynamic therapy.
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BIOMATERIALS
·
2025
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IF 12.9
Yingjie Ren,Qin Fan,Xinhao Yao,Jinqiao Zhang,Kexin Wen,Xinran Qu,Bicheng Sun,Han Wu,Ziliang Dong
Tumor heterogeneity disrupts the consistent expression of target markers, leading to inefficient tumor targeting and contributing to drug resistance and relapse. Therefore, seeking a more universal target is crucial for enhancing drug enrichment in tumors. In this study, we propose a self-amplifying tumor-targeting strategy that leverages externalized phosphatidylserine (PtdSer) on apoptotic cells as a universal target. The system is composed of a Red Blood Cell-Liposome hybrid membrane camouflaged Mn–Ce6 nanocomplex, which is further modified with a PtdSer aptamer (MC@RL/Apt). MC@RL/Apt demonstrates prolonged circulation time and enhanced tumor accumulation, capable of inducing cancer cell apoptosis and PtdSer externalization under 660 nm light irradiation. The externalized PtdSer is then recognized by the PtdSer aptamer, which recruits additional MC@RL/Apt to the tumor site, facilitating a self-amplified tumor accumulation effect. In vitro studies show that MC@RL/Apt acted as an efferocytosis inhibitor, suppressing macrophage phagocytosis of apoptotic cells and promoting macrophage polarization toward the pro-inflammatory M1 phenotype. Compared to non-functionalized MC@RL, intravenous administration of MC@RL/Apt increases tumor accumulation by 1.46-fold under 660 nm light irradiation. As a result, treatment with MC@RL/Apt effectively suppressed tumor growth and induced robust antitumor immune responses. This work highlights a self-amplifying tumor-targeting strategy that leverages externalized PtdSer on apoptotic cells as a target to enhance tumor-specific drug delivery, while simultaneously inhibiting PtdSer-mediated macrophage engulfment, offering a promising approach for improving cancer therapy outcomes.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yu Wang,Teng Wang,Tianze Jiang,Bingjie Wang,Yanguo Su,Tiantian Gan,Xia Zhao
In situ cancer vaccines are a more promising immunotherapeutic strategy than traditional cancer vaccines. However, its clinical application is hindered by insufficient exposure and presentation of tumor-associated antigens (TAAs). Here, we report a co-delivery hydrogel (CCFA@Gel) based on autophagy and efferocytosis as a “cancer vaccine factory” to enhance tumor immunotherapy. CCFA@Gel is a temperature-sensitive hydrogel composed of fucoidan (Fuc)-coated chlorin e6 (Ce6)-chloroquine (CQ) self-assembly and apocynin (APO). After CCFA@Gel targeting tumor cells through the affinity of Fuc to P-selectin, Ce6 induces immunogenic cell death (ICD) by photodynamic therapy (PDT) to trigger the exposure of TAAs. CQ enhances the retention of TAAs by inhibiting autophagy, while APO enhances the presentation of TAAs by inhibiting the efferocytosis of tumor-associated macrophages (TAMs). In vivo results show that CCFA@Gel significantly inhibits primary tumors, as well as tumor metastasis and recurrence by enhancing the exposure, retention and presentation of TAAs. Our study provides a novel strategy for in situ vaccines development to enhance cancer immunotherapy.
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