Guangbao Yang  Soo Zeng Fiona Phua  Wei Qi Lim  Rui Zhang  Liangzhu Feng  Guofeng Liu  Hongwei Wu  Anivind Kaur Bindra  Deblin Jana  Zhuang Liu  Yanli Zhao 《Advanced materials (Deerfield Beach, Fla.)》2019,31(25)

Uncontrolled cancer cell proliferation, insufficient blood flow, and inadequate endogenous oxygen lead to hypoxia in tumor tissues. Herein, a unique type of hypoxia‐responsive human serum albumin (HSA)‐based nanosystem (HCHOA) is reported, prepared by cross‐linking the hypoxia‐sensitive azobenzene group between photosensitizer chlorin e6 (Ce6)‐conjugated HSA (HC) and oxaliplatin prodrug‐conjugated HSA (HO). The HCHOA nanosystem is stable under normal oxygen partial pressure with a size of 100–150 nm. When exposed to the hypoxic tumor microenvironment, the nanosystem can quickly dissociate into ultrasmall HC and HO therapeutic nanoparticles with a diameter smaller than 10 nm, significantly enabling their enhanced intratumoral penetration. After the dissociation, the quenched fluorescence of Ce6 in the produced HC nanoparticles can be recovered for bioimaging. At the same time, the production of singlet oxygen is increased because of the enhancement in the photoactivity of the photosensitizer. On account of these improvements, combined photodynamic therapy and chemotherapy is realized to display superior antitumor efficacy in vivo. Based on this simple strategy, it is possible to achieve the dissociation of hypoxic‐responsive nanosystem to enhance the tumor penetration and therapeutic effect.  相似文献   

    

Wei Xiong  Ziyi Cheng  Hongwei Chen  Huixian Liang  Miao Wang  Yan Chen  Junyu Ying  Yizhou Cai  Jinxuan Chai  Kun Dou  Wuping Zheng  Shaojiang Zheng  Linlu Zhao 《Advanced functional materials》2024,34(52):2410841

To advance the understanding and potential treatment strategies for triple-negative breast cancer (TNBC), particularly focusing on its high metastatic propensity and uncertain molecular targets, a biomimetic tumor cell membrane-encapsulated nanodelivery system is developed for enhanced immunotherapy. This system is assembled with the second near-infrared (NIR-II) photothermal agent, chemotherapeutic drug, and programmed death-ligand 1 (PD-L1) inhibitors camouflaged by TNBC cell membranes. An NIR-II Ag₂S quantum dots (QDs) is introduced for not only realizing pronounced imaging-guided photothermal therapy (PTT), but also co-activating immunogenic cell death (ICD) with chemotherapy. Homologous targeting and camouflage properties endowed the nanodelivery system with excellent biocompatibility and efficient delivery ability to the tumor site, demonstrating excellent synergistic therapeutic efficacy. The release of damage-associated molecular patterns (DAMP) marked the induction of ICD, crucial for reshaping the immune microenvironment. Further integration of α-PD-L1 achieved a 56.5% immune checkpoint inhibition rate, synergistically amplifying immune response to ultimately activate key cytokines, thereby achieving pronounced anti-tumor immunotherapy effects. Notably, this approach realized a considerable reduction of metastatic nodules by 51.2% in the TNBC lung metastasis model. The proposed nanodelivery system extended tumor remission and effectively reduced lung metastasis, paving the way for a reliable and promising approach in TNBC immunotherapy.  相似文献   

    

Dr. Yanyan Huang  Prof. Dr. Guanxin Zhang  Prof. Dr. Rui Zhao  Prof. Dr. Deqing Zhang 《ChemMedChem》2020,15(23):2220-2227

The importance of mitochondria in tumorigenesis makes these organelles an ideal target for cancer therapy. In recent years, luminogens with the aggregation-induced emission (AIE) effect have been developed for mitochondrial targeting and cancer treatment. The induction of mitochondrial dysfunction can be an effective pathway of chemotherapy, photodynamic therapy, and combination therapy against cancer. This review focuses on recent progress in the field of AIE luminogens (AIEgens) for cancer theranostics based on mitochondrial targeting and dysfunction. AIEgens for cancer treatment, including chemotherapy, photodynamic therapy, and combination therapy, are summarized herein. Molecular design efforts toward mitochondrial targeting and mitochondria-damaging mechanisms are also discussed. Finally, we discuss the challenges and future directions of development for AIEgens in mitochondria-targeted cancer treatment.  相似文献   

    

Abdur Rauf;Zuneera Akram;Nabia Hafeez;Anees Ahmed Khalil;Ahood Khalid;Hassan A. Hemeg;Abdullah S. M. Aljohani;Waleed Al Abdulmonem;Mohammed Mansour Quradha;Abdulkader Moqbel Farhan Qahtan; 《Food Science & Nutrition》2024,12(9):6047-6054

Cancer, characterized as one of the leading causes of death owing to its heterogeneity and complexity, hence poses a significant challenge to health care system across the globe. Current therapies for cancer curtailment are considered to have associated side effects, therefore discovery of novel alternative approaches is need of the time. In this context, natural products have attained an essential spot in the scientific community for the development of novel cancer treatments. Among others, Diospyrin, a bis-hydroxy-naphthoquinonoid, is a vital bioactive component present in various Diospyros and Euclea species. The bioactivity associated with Diospyrin's makes it a promising “lead molecule” for new chemotherapy. In this review, biosynthesis of Diospyrin and its analogues along with their anticancer activities has been discussed. Moreover, this review briefly discusses probable modes of action of Diospyrin and its analogues by targeting the molecular signal transduction pathways. This review also highlights the toxicological and clinical implications of diospyrin and its derivatives. Further pharmacological and pharmacogenetic studies are required to better understand the anticancer potential of Diospyrin and its analogues at the molecular and genetic levels.  相似文献   

    

Ronnie Solomon  Ali AbuMadighem  Joseph Kapelushnik  Bat-Chen Amano  Eitan Lunenfeld  Mahmoud Huleihel 《International journal of molecular sciences》2021,22(4)

Aggressive chemotherapy treatment may lead to male infertility. Prepubertal boys do not produce sperm at this age, however, they have spermatogonial stem cells in their testes. Here, we examined the effect of intraperitoneal injection of cyclophosphamide (CP) on the capacity of immature mice (IM) to develop spermatogenesis in vivo and in vitro [using methylcellulose culture system (MCS)]. Our results show a significant decrease in testicular weight, total number of testicular cells, and the number of Sertoli, peritubular, premeiotic, and meiotic/post-meiotic cells, but an increase in the percentages of damaged seminiferous tubules in CP-treated IM compared to control. The functionality of Sertoli cells was significantly affected. The addition of testosterone to isolated cells from seminiferous tubules of CP-treated IM significantly increased the percentages of premeiotic (CD9-positive cells) and meiotic/post-meiotic cells (ACROSIN-positive cells) developed in MCS compared to control. The addition of FSH did not affect developed cells in MCS compared to control, but in combination with testosterone, it significantly decreased the percentages of CD9-positive cells and ACROSIN-positive cells. The addition of IL-1 did not affect developed cells in MCS compared to control, but in combination with testosterone, it significantly increased the percentages of VASA-positive cells and BOULE-positive cells compared to IL-1 or testosterone. Addition of TNF significantly increased only CD9-positive cells in MCS compared to control, but in combination with testosterone, it significantly decreased ACROSIN-positive cells compared to testosterone. Our results show a significant impairment of spermatogenesis in the testes of CP-treated IM, and that spermatogonial cells from these mice proliferate and differentiate to meiotic/post-meiotic cells under in vitro culture conditions.  相似文献   

    

Yiwei Wang  Liuyue Xu  Shanshan Shi  Sha Wu  Ruijie Meng  Huifang Chen  Zhenyou Jiang 《International journal of molecular sciences》2021,22(8)

Acquired treatment resistance is an important cause of death in prostate cancer, and this study aimed to explore the mechanisms of chemotherapy resistance in prostate cancer. We employed castration-resistant prostate cancer (CRPC), neuroendocrine prostate cancer (NEPC), and chemotherapy-resistant prostate cancer datasets to screen for potential target genes. The Cancer Genome Atlas (TCGA) was used to detect the correlation between the target genes and prognosis and clinical characteristics. Nei endonuclease VIII-like 3 (NEIL3) knockdown cell lines were constructed with RNA interference. Prostate cancer cells were treated with enzalutamide for the androgen deprivation therapy (ADT) model, and with docetaxel and cisplatin for the chemotherapy model. Apoptosis and the cell cycle were examined using flow cytometry. RNA sequencing and western blotting were performed in the knockdown Duke University 145 (DU145) cell line to explore the possible mechanisms. The TCGA dataset demonstrated that high NEIL3 was associated with a high T stage and Gleason score, and indicated a possibility of lymph node metastasis, but a good prognosis. The cell therapy models showed that the loss of NEIL3 could promote the chemotherapy resistance (but not ADT resistance) of prostate cancer (PCa). Flow cytometry revealed that the loss of NEIL3 in PCa could inhibit cell apoptosis and cell cycle arrest under cisplatin treatment. RNA sequencing showed that the knockdown of NEIL3 changes the expression of neuroendocrine-related genes. Further western blotting revealed that the loss of NEIL3 could significantly promote the phosphorylation of ATR serine/threonine kinase (ATR) and ATM serine/threonine kinase (ATM) under chemotherapy, thus initiating downstream pathways related to DNA repair. In summary, the loss of NEIL3 promotes chemotherapy resistance in prostate cancer, and NEIL3 may serve as a diagnostic marker for chemotherapy-resistant patients.  相似文献   

    

Malgorzata Chmielewska-Kassassir  Lucyna A. Wozniak 《International journal of molecular sciences》2021,22(15)

Malignant pleural mesothelioma (MPM) is a rare but highly aggressive tumor of pleura arising in response to asbestos fibers exposure. MPM is frequently diagnosed in the advanced stage of the disease and causes poor prognostic outcomes. From the clinical perspective, MPM is resistant to conventional treatment, thus challenging the therapeutic options. There is still demand for improvement and sensitization of MPM cells to therapy in light of intensive clinical studies on chemotherapeutic drugs, including immuno-modulatory and targeted therapies. One way is looking for natural sources, whole plants, and extracts whose ingredients, especially polyphenols, have potential anticancer properties. This comprehensive review summarizes the current studies on natural compounds and plant extracts in developing new treatment strategies for MPM.  相似文献   

    

Chun-I Wang  Pei-Ming Chu  Yi-Li Chen  Yang-Hsiang Lin  Cheng-Yi Chen 《International journal of molecular sciences》2021,22(24)

Hepatocellular carcinoma (HCC), the most common type of liver cancer, is the second leading cause of cancer-related mortality worldwide. Processes involved in HCC progression and development, including cell transformation, proliferation, metastasis, and angiogenesis, are inflammation-associated carcinogenic processes because most cases of HCC develop from chronic liver damage and inflammation. Inflammation has been demonstrated to be a crucial factor inducing tumor development in various cancers, including HCC. Cytokines play critical roles in inflammation to accelerate tumor invasion and metastasis by mediating the migration of immune cells into damaged tissues in response to proinflammatory stimuli. Currently, surgical resection followed by chemotherapy is the most common curative therapeutic regimen for HCC. However, after chemotherapy, drug resistance is clearly observed, and cytokine secretion is dysregulated. Various chemotherapeutic agents, including cisplatin, etoposide, and 5-fluorouracil, demonstrate even lower efficacy in HCC than in other cancers. Tumor resistance to chemotherapeutic drugs is the key limitation of curative treatment and is responsible for treatment failure and recurrence, thus limiting the ability to treat patients with advanced HCC. Therefore, the capability to counteract drug resistance would be a major clinical advancement. In this review, we provide an overview of links between chemotherapeutic agents and inflammatory cytokine secretion in HCC. These links might provide insight into overcoming inflammatory reactions and cytokine secretion, ultimately counteracting chemotherapeutic resistance.  相似文献   

    

Tao-Chieh Yang  Shih-Jung Liu  Wei-Lun Lo  Shu-Mei Chen  Ya-Ling Tang  Yuan-Yun Tseng 《International journal of molecular sciences》2021,22(11)

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.  相似文献   

    

Francesca Mo  Alessia Pellerino  Riccardo Soffietti  Roberta Rud 《International journal of molecular sciences》2021,22(23)

The presence of barriers, such as the blood–brain barrier (BBB) and brain–tumor barrier (BTB), limits the penetration of antineoplastic drugs into the brain, resulting in poor response to treatments. Many techniques have been developed to overcome the presence of these barriers, including direct injections of substances by intranasal or intrathecal routes, chemical modification of drugs or constituents of BBB, inhibition of efflux pumps, physical disruption of BBB by radiofrequency electromagnetic radiation (EMP), laser-induced thermal therapy (LITT), focused ultrasounds (FUS) combined with microbubbles and convection enhanced delivery (CED). However, most of these strategies have been tested only in preclinical models or in phase 1–2 trials, and none of them have been approved for treatment of brain tumors yet. Concerning the treatment of brain metastases, many molecules have been developed in the last years with a better penetration across BBB (new generation tyrosine kinase inhibitors like osimertinib for non-small-cell lung carcinoma and neratinib/tucatinib for breast cancer), resulting in better progression-free survival and overall survival compared to older molecules. Promising studies concerning neural stem cells, CAR-T (chimeric antigen receptors) strategies and immunotherapy with checkpoint inhibitors are ongoing.  相似文献