Bioorganic Chemistry最新文献

{"title":"Benzylpiperidine derivatives as new dual μ-opioid and σ₁ receptor ligands with potent antinociceptive effects.","authors":"Zong-Zheng Li, Zhen Wang, Xiong Chen, Hong-Qing Feng, Xing-Yu Yao, Jie Song, Ben Xu, Jian Jin, Xudong Cao, Tao Zhuang","doi":"10.1016/j.bioorg.2024.107921","DOIUrl":"10.1016/j.bioorg.2024.107921","url":null,"abstract":"<p><p>Dual-acting μ-opioid receptor (MOR)/sigma-1 receptor (σ₁R) ligands have displayed promise in exerting robust antinociceptive effects while reducing opioid-related side effects. To discover safer and more effective analgesics, we designed, prepared, and evaluated 30 benzylpiperidine derivatives as dual MOR and σ₁R ligands. The obtained benzylpiperidine analogs were tested for MOR and σ₁R binding affinity in vitro. The best compound 52 showed high affinity for both MOR [K_i (MOR) = 56.4 nM] and σ₁R [K_i (σ₁R) = 11.0 nM] and produced potent antinociceptive effects in the abdominal contraction test (ED₅₀ = 4.04 mg/kg in mice), carrageenan-induced inflammatory pain model (ED₅₀ = 6.88 mg/kg in mice), formalin test (ED₅₀ = 13.98 mg/kg in rats) and complete Freund's adjuvant (CFA)-induced chronic pain model (ED₅₀ = 7.62 mg/kg in mice). Moreover, 52 had less MOR-related adverse effects than oxycodone, including constipation, acute hyperlocomotion and physical dependence. The above results suggested that 52 may be a promising candidate for the development of safer analgesics.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107921"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eco-conscious synthesis of novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives as potent Anti-microbial agent and comparative study of cell viability and cytotoxicity in HEK-293 cell line utilizingIndian gooseberry (Phyllanthus emblica) fruit extract.","authors":"Bhaktiben R Bhatt, Kamalkishor Pandey, Tarosh Patel, Anupama Modi, Chandani Halpani, Vaibhav D Bhatt, Bharat C Dixit","doi":"10.1016/j.bioorg.2024.107936","DOIUrl":"10.1016/j.bioorg.2024.107936","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) is a pressing global health challenge that necessitates the search for novel antimicrobial agents and synthetic methodologies. This study investigates the synthesis and antimicrobial efficacy of 25 novel 1,2,4-triazolo[1,5-a]pyrimidine derivatives, catalyzed by Amla (Phyllanthus emblica) fruit juice, which is rich in organic acids and polyphenolic compounds, thus serving as an environmentally sustainable catalyst, in adherence to green chemistry principles. The synthesis is achieved through a one-pot, solvent-free process that yields high quantities of the desired compounds in significantly less time compared to traditional methods. Comprehensive antimicrobial evaluation was conducted against a range of clinically relevant microorganisms, including Chromobacterium violaceum, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Candida albicans, Cryptococcus neoformans and Aspergillus niger. Concurrently, cytotoxic assays were performed on HEK-293 cells, to assess safety profiles, revealing that compounds B-1, B-6, B-7, B-14 and B-15 exhibited potent antimicrobial activity while maintaining low cytotoxicity and high cell viability. These findings underscore the therapeutic potential of the synthesized compounds in combatting infectious diseases and addressing the challenges posed by AMR, highlighting the critical importance of dose optimization in therapeutic applications. This study combats contagious diseases, mitigates AMR challenges and contributes significantly to the field of antimicrobial drug discovery, emphasizing the need for sustainable synthetic strategies that align with future pharmaceutical endeavors. Our research not only advances the understanding of these novel compounds but also supports ongoing efforts to develop safe and effective therapies against resistant pathogens.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107936"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"X-ray induced in-situ ferroptosis through the Fenton reaction of iron supplements for the cancer therapy.","authors":"Wang Qian, Caiju Zhang, Li He, Shiqi Jin, Ruiyang Suo, Yi Li, Shuqi Li, Ling Zhu, Kai Deng, Bo Wu, Yongchang Wei","doi":"10.1016/j.bioorg.2024.108021","DOIUrl":"https://doi.org/10.1016/j.bioorg.2024.108021","url":null,"abstract":"<p><p>The potential of iron-based therapeutic agents in enhancing radiotherapy efficacy through catalyzing the Fenton reaction has garnered widespread interest. The inherent instability of ferrous ions requires the use of complex ligands for the ligand-dependent reduction from Fe³⁺ to Fe²⁺, thereby boosting ferroptosis through inducing the Fenton reaction. However, the reliance on complex redox systems and potential long-term toxicity have seriously limited the clinical application in cancer treatment. In this study, we propose an innovative approach that utilizes the reduction capabilities of hydrated electrons generated by X-ray to directly reduce both ferric ions (Fe³⁺) and Iron Proteinsuccinylate, a clinically used iron supplement. Our experiments showed that over 20 % of Fe³⁺, at a concentration of 23 μM, was reduced by X-ray without the need for ligand involvement. Furthermore, both in vitro and in vivo studies confirmed that Iron Proteinsuccinylate exhibited the highest tumor growth inhibition rate through the Fenton reaction and ferroptosis, offering a new and safer method for the in-situ reduction of Fe³⁺ and enhancing the efficacy of radiotherapy.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"154 ","pages":"108021"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing potential COX-2 engagement for boosting anticancer activity of substituted 2-mercapto-4(3H)-quinazolinones with promising EGFR/VEGFR-2 inhibitory activities.","authors":"Abdelrahman Hamdi, Samar S Tawfik, Ahmed R Ali, Wafaa A Ewes, Abdullah Haikal, Adel S El-Azab, Ahmed H Bakheit, Mohamed M Hefnawy, Hazem A Ghabbour, Alaa A-M Abdel-Aziz","doi":"10.1016/j.bioorg.2024.107951","DOIUrl":"10.1016/j.bioorg.2024.107951","url":null,"abstract":"<p><p>We designed and synthesized new quinazolinone-tethered phenyl thiourea/thiadiazole derivatives 4-26. Based on their structural characteristics, these compounds were proposed to have a multi-target mode of action for their anticancer activities. Using the MTT assay method, antiproliferative effects were assessed against three human cancer cell lines (HEPG-2, MCF-7, and HCT-116). In vitro assessment for enzymatic inhibitory activity of the most active compounds 4, 9 and 20 was done for EGFR, VEGFR-2 and COX-2 as potential targets. The screened compounds showed low micromolar IC₅₀ inhibitory effects against the three targets. Compound 9 demonstrated similar EGFR/VEGFR-2 inhibitory effect to the control drugs and potential inhibitory activity for COX-2 enzyme. In MCF-7 cells, the most active analog 9 caused 41.02% total apoptosis, and arrested the cell cycle at the G2/M phase. Taken as a whole, the findings of this study provide significant new understandings into the relationship between COX inhibition and cancer therapy. Furthermore, the outcomes showcased the encouraging efficacy of these compounds with a multi-target mechanism, making them excellent choices for additional research and development into possible anticancer drug.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107951"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and structural proof of novel oxazolo[5,4-d]pyrimidine derivatives as potential VEGFR2 inhibitors. In vitro study of their anticancer activity.","authors":"Aleksandra Sochacka-Ćwikła, Andrzej Regiec, Żaneta Czyżnikowska, Urszula Śliwińska-Hill, Anna Kwiecień, Benita Wiatrak, Agnieszka Rusak, Klaudia Krawczyńska, Monika Mrozowska, Sylwia Borska, Katarzyna Ratajczak, Anna Pyra, Marcin Mączyński","doi":"10.1016/j.bioorg.2024.107958","DOIUrl":"10.1016/j.bioorg.2024.107958","url":null,"abstract":"<p><p>The present study aimed to design and synthesize novel 6-N-benzyloxazolo[5,4-d]pyrimidin-7(6H)-imines 3a-j as possible inhibitors of the vascular endothelial growth factor receptor 2 (VEGFR2). The structures of newly synthesized compounds were confirmed via spectral and crystallographic data. NOESY spectroscopy was very useful in distinguishing between 6-N-benzyl-7(6H)-imine 3a and isomeric 7-N-benzyl-7-amine 4a, obtained by Dimroth rearrangement. Molecular docking at the VEGFR2 active site was performed, indicating that 7(6H)-imines should have a similar binding mode as type II VEGFR2 inhibitors. All derivatives were preliminary evaluated for in vitro cytotoxic activity against four human cancer cell lines, including lung cancer (A549), colorectal cancer (HT-29), melanoma (A375), breast cancer (MCF7), using tivozanib as a reference drug, and some of them were subjected to VEGFR2 inhibition, anti-angiogenic activity, and human serum albumin (HSA) binding assays. Only 6-N-2,4-dimethoxybenzyl derivative 3h appeared to be as active as tivozanib against all tested anticancer cell lines but equally toxic to healthy normal human dermal fibroblasts (NHDF). Derivatives 3f (6-N-2-methybenzyl) and 3b (6-N-4-methylbenzyl) have revealed slightly worse activity than 3h. They were cytotoxic agents comparable to tivozanib against three anticancer lines, but only 3b showed no cytotoxicity against NHDF. Both 3b and 3h proved to be effective VEGFR2 inhibitors with IC₅₀ values comparable to that of tivozanib. Notably, 4a did not actually show an anticancer effect against the tested cancer lines, in contrast to isomeric 3a. In an angiogenesis assay, 3f and 3h significantly suppressed the tube formation ability of human dermal microvascular endothelial cells (HMEC-1), indicating their anti-angiogenic potential. The interactions between these compounds and HSA appeared to occur at two specific binding sites.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107958"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemo-enzymatic synthesis of NPN cofactor taking advantage of ADP-ribosyl cyclase and LarC cyclometallase promiscuous activities.","authors":"Timothé Vucko, Dmytro Strilets, Patrice Soumillion, Benoît Desguin, Stéphane P Vincent","doi":"10.1016/j.bioorg.2024.107879","DOIUrl":"10.1016/j.bioorg.2024.107879","url":null,"abstract":"<p><p>The nickel-pincer nucleotide cofactor (NPN) is a widespread organometallic cofactor required for lactate racemase (LarA) and for α-hydroxy acid racemases and epimerases of the LarA superfamily. Its biosynthesis, which starts with nicotinic acid adenine dinucleotide (NaAD), requires three enzymes: LarB, LarC, and LarE, and can be performed in vitro with purified enzymes. Nevertheless, as LarE and LarC are single turnover enzymes, the in vitro NPN biosynthesis requires huge amounts of enzymes (particularly 2 equivalents of LarE), which hampers the study of NPN and of NPN-dependent enzymes. By using adenosine diphosphate (ADP)-ribosyl cyclase (ARC), we exchanged the nicotinamide moiety in NAD⁺ with synthetic pyridine-3,5-bisthiocarboxylic acid in order to synthesize the novel intermediate pyridinium-3,5-bisthiocarboxylic acid adenine dinucleotide (P2TAD). The latter could be produced at a multimilligram scale allowing its characterization by Nuclear Magnetic Resonance (NMR) and mass spectrometry. Interestingly, P2TAD could directly be used by LarC in order to generate the NPN cofactor, bypassing both LarB and LarE. Globally, a new chemoenzymatic route towards NPN was developed via the intermediate P2TAD, which should facilitate the biochemical and biotechnological investigations on NPN binding enzymes.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107879"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142454440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rivastigmine structure-based hybrids as potential multi-target anti-Alzheimer's drug candidates.","authors":"Rosalba Leuci, Stefan Simic, Antonio Carrieri, Sílvia Chaves, Gabriella La Spada, Leonardo Brunetti, Paolo Tortorella, Fulvio Loiodice, Antonio Laghezza, Marco Catto, M Amélia Santos, Vincenzo Tufarelli, Judith Wackerlig, Luca Piemontese","doi":"10.1016/j.bioorg.2024.107895","DOIUrl":"10.1016/j.bioorg.2024.107895","url":null,"abstract":"<p><p>In recent years, an increasing amount of work has been carried out regarding the study of the etiopathology of Alzheimer's Disease (AD). This neurodegenerative disease is characterized by several organic and molecular correlates, which paint a complex picture that also reflects the historic challenge faced by the worldwide scientific community in finding an effective cure for it. In this paper, we describe the synthesis of novel rivastigmine derivatives and their characterization as wide-spectrum enzyme (AChE, BChE, FAAH, MAO-A and MAO-B) inhibitors with potential application in the therapy of AD following the paradigm of multi-target design. 5 (ROS151) and 23 show similar inhibitory profile compared to donepezil on cholinesterases, and ca. two hundred twenty-three and eighty-seven times more active than rivastigmine on AChE. Moreover, ROS151 was found to be a potential metal chelator. Compounds 6 and 8 are very interesting and original multi-functional promising hybrids, with comparable potency on distinct panels of enzymes. All these promising rivastigmine-like hybrids were assayed for their pharmacokinetic properties by using different bio-analytical techniques, showing interesting applicability profiles. Moreover, cytotoxicity assays displayed a safety profile on three different cell lines.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107895"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of new 4-aminoquinoline derivatives containing an amine or hydroxamic acid terminal as multifunctional agents for the treatment of Alzheimer's disease.","authors":"Bochao Zhai, Qianyun Hao, Mingfan Wang, Zhiqiang Luo, Rui Yang, Jian Yang, Yuqing Cao","doi":"10.1016/j.bioorg.2024.107954","DOIUrl":"10.1016/j.bioorg.2024.107954","url":null,"abstract":"<p><p>Due to the multifactorial nature of Alzheimer's disease (AD), effective multi-targeted directed ligands (MTDLs) are urgently needed for its treatment as single-target drugs currently encounter therapeutic challenges. Two series of new 4-aminoquinoline derivatives containing an amine or hydroxamic acid terminal were designed, synthesized and evaluated for their cholinesterase inhibition, antioxidant and metal-ion chelation properties. Among them, hydroxamic acid-containing compounds 7r and 7f exhibited the best inhibitor activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), respectively, with the corresponding IC₅₀ values of 0.41 and 1.06 μM, which were superior to those of rivastigmine (IC₅₀ = 5.26, 2.02 μM, respectively). Moreover, compounds 7r and 7f presented excellent ABTS radical scavenging efficiency and selective metal-ion chelation ability such as Cu²⁺ and Fe²⁺. Both molecular docking and enzyme kinetic analysis revealed that compound 7r was a mixed-type inhibitor of AChE. Additionally, the ADME prediction indicated that compounds 7r and 7f have suitable pharmacokinetic and drug-like properties. Furthermore, they demonstrated good safety and blood-brain barrier permeability in cytotoxicity assays and in vivo experiments, respectively. These findings strongly suggest that the 4-aminoquinoline derivatives containing a hydroxamic acid terminal have great potential as promising MTDLs for the treatment of AD, opening new avenues for future therapeutic strategies.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107954"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baliosperoid A attenuates lipopolysaccharide-induced acute lung injury by targeting SHP2 to inhibit inflammation and oxidative stress.","authors":"Yue Li, Lirong Zhao, Zhaoxia Liu, Ying Chen, Xiaoqin Li, Dongrong Zhu, Liren Liu","doi":"10.1016/j.bioorg.2024.107982","DOIUrl":"10.1016/j.bioorg.2024.107982","url":null,"abstract":"<p><p>Acute lung injury (ALI) remains a devastating clinical condition with limited therapeutic options. While Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2) has emerged as a critical mediator in ALI pathogenesis, effective SHP2-targeting therapeutics remain largely elusive. Baliospermum solanifolium (Burm.) is a traditional medicine used to treat various diseases such as asthma, edema, bronchitis, jaundice, and constipation. Baliosperoid A (BA), a diterpenoid compound derived from Baliospermum solanifolium's roots, exhibits potent NO inhibitory activity in RAW264.7 cells. However, its anti-inflammatory activity and potential targets have never been reported. Here, we report BA acts as a selective SHP2 inhibitor with remarkable therapeutic potential against ALI. Through comprehensive molecular and functional analyses, we demonstrate that BA directly binds to and inhibits SHP2 phosphatase activity with high specificity (IC₅₀ = 1.638 ± 0.324 μM). Mechanistically, BA orchestrates a dual-action therapeutic effect by simultaneously suppressing inflammatory cascades through SHP2-mediated MAPK and NF-κB pathway inhibition while activating the Nrf2-dependent antioxidant response. In preclinical models of ALI and sepsis, BA treatment significantly improved survival rates, preserved lung architecture, and prevented multi-organ dysfunction. Notably, BA demonstrated superior efficacy to the existing SHP2 inhibitor SHP099, particularly in sepsis survival outcomes (90 % vs 50 % survival at 24 h). Our findings not only identify BA as a promising therapeutic candidate for ALI but also establish a novel paradigm for targeting SHP2 in inflammatory diseases.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107982"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel co-delivery nanomedicine for photodynamic enlarged immunotherapy by cascade immune activation and efficient Immunosuppression reversion.","authors":"Yimei Zhang, Shiyi Xiang, Yayi Wu, Can Yang, Dianyong Tang, Zhongzhu Chen, Zheng Huang","doi":"10.1016/j.bioorg.2024.107978","DOIUrl":"10.1016/j.bioorg.2024.107978","url":null,"abstract":"<p><p>Photodynamic therapy (PDT) combined with immunotherapy has become a promising antitumor strategy. However, precise regulation of the activation of antitumor immunity and effective reversion of immunosuppressive tumor microenvironment (TME) remains challenging. In this paper, a novel co-delivery nanomedicine is developed to solve these issues for photodynamic amplified immunotherapy. Specifically, the glycolysis inhibitor (Lon) is coupled with PD1/PDL1 blocker (BMS-1) by thioketal linkage to form smartly responsive prodrug LTB, which could further encapsulate photosensitizer chlorine e6 (Ce6) to construct a co-delivery nanoplatform (LTB-6 NPs) by self-assembly. Of note, LTB-6 NPs possess favorable stability, uniform morphology and improved cellular uptake. More importantly, LTB-6 NPs are capable of inhibiting glycolysis and blocking PD1/PDL1, which could greatly improve the immunosuppressive TME to promote immune activation. LTB-6 NPs-mediated PDT not only inhibits tumor proliferation but also induces ICD response to activate immunological cascade. In vivo experiments indicate that intravenously injected LTB-6 NPs remarkably suppresses the tumor growth while leads to a minimized side effect. This research provides a multi-synergized strategy for developing effective photodynamic nanoplatforms in tumor treatment.</p>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"153 ","pages":"107978"},"PeriodicalIF":4.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}