Pub Date : 2024-08-01DOI: 10.1016/j.ajps.2024.100939
Ferroptosis is a nonapoptotic form of cell death characterized by iron dependence and lipid peroxidation. Ferroptosis is involved in a range of pathological processes, such as cancer. Many studies have confirmed that ferroptosis plays an essential role in inhibiting cancer cell proliferation. In addition, a series of small-molecule compounds have been developed, including erastin, RSL3, and FIN56, which can be used as ferroptosis inducers. The combination of ferroptosis inducers with anticancer drugs can produce a significant synergistic effect in cancer treatment, and patients treated with these combinations exhibit a better prognosis than patients receiving traditional therapy. Therefore, a thorough understanding of the roles of ferroptosis in cancer is of great significance for the treatment of cancer. This review mainly elaborates the molecular biological characteristics and mechanism of ferroptosis, summarizes the function of ferroptosis in cancer development and treatment,illustrates the application of ferroptosis in patient's prognosis prediction and drug discovery, and discusses the prospects of targeting ferroptosis.
{"title":"Recent progress of ferroptosis in cancers and drug discovery","authors":"","doi":"10.1016/j.ajps.2024.100939","DOIUrl":"10.1016/j.ajps.2024.100939","url":null,"abstract":"<div><p>Ferroptosis is a nonapoptotic form of cell death characterized by iron dependence and lipid peroxidation. Ferroptosis is involved in a range of pathological processes, such as cancer. Many studies have confirmed that ferroptosis plays an essential role in inhibiting cancer cell proliferation. In addition, a series of small-molecule compounds have been developed, including erastin, RSL3, and FIN56, which can be used as ferroptosis inducers. The combination of ferroptosis inducers with anticancer drugs can produce a significant synergistic effect in cancer treatment, and patients treated with these combinations exhibit a better prognosis than patients receiving traditional therapy. Therefore, a thorough understanding of the roles of ferroptosis in cancer is of great significance for the treatment of cancer. This review mainly elaborates the molecular biological characteristics and mechanism of ferroptosis, summarizes the function of ferroptosis in cancer development and treatment,illustrates the application of ferroptosis in patient's prognosis prediction and drug discovery, and discusses the prospects of targeting ferroptosis.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.7,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000564/pdfft?md5=37c620413ddc9b28ac4bec93dfd13a5f&pid=1-s2.0-S1818087624000564-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141572417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.ajps.2024.100910
Xuyao Liu , Qi Shi , Peng Qi , Ziming Wang , Tongyue Zhang , Sijia Zhang , Jiayan Wu , Zhaopei Guo , Jie Chen , Qiang Zhang
The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer. Currently, living cell nucleic acid probes, which enable the in situ imaging and dynamic monitoring of nucleic acids, have become a rapidly developing field. This review focuses on living cell nucleic acid probes that can be used for the early diagnosis of tumors. We describe the fundamental design of the probe in terms of three units and focus on the roles of different nanomaterials in probe delivery.
{"title":"Recent advances in living cell nucleic acid probes based on nanomaterials for early cancer diagnosis","authors":"Xuyao Liu , Qi Shi , Peng Qi , Ziming Wang , Tongyue Zhang , Sijia Zhang , Jiayan Wu , Zhaopei Guo , Jie Chen , Qiang Zhang","doi":"10.1016/j.ajps.2024.100910","DOIUrl":"10.1016/j.ajps.2024.100910","url":null,"abstract":"<div><p>The early diagnosis of cancer is vital for effective treatment and improved prognosis. Tumor biomarkers, which can be used for the early diagnosis, treatment, and prognostic evaluation of cancer, have emerged as a topic of intense research interest in recent years. Nucleic acid, as a type of tumor biomarker, contains vital genetic information, which is of great significance for the occurrence and development of cancer. Currently, living cell nucleic acid probes, which enable the <em>in situ</em> imaging and dynamic monitoring of nucleic acids, have become a rapidly developing field. This review focuses on living cell nucleic acid probes that can be used for the early diagnosis of tumors. We describe the fundamental design of the probe in terms of three units and focus on the roles of different nanomaterials in probe delivery.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000278/pdfft?md5=b86a6ad335897822d142540e1f939d93&pid=1-s2.0-S1818087624000278-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140801206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.ajps.2024.100912
Cuixia Zheng , Lingling Sun , Hongjuan Zhao , Mengya Niu , Dandan Zhang , Xinxin Liu , Qingling Song , Weijie Zhong , Baojin Wang , Yun Zhang , Lei Wang
Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer. However, the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations. Furthermore, monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors. In this study, based on our discovery that spore shell (SS) of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity, we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy, chemodynamic therapy and antitumor immunity for synergistic cancer treatment. In detail, SS is separated from probiotic spores and then attached to the surface of liposome (Lipo) that was loaded with hemoglobin (Hb), glucose oxidase (GOx) and JQ1 to construct SS@Lipo/Hb/GOx/JQ1. In tumor tissue, highly toxic hydroxyl radicals (•OH) are generated via sequential catalytic reactions: GOx catalyzing glucose into H2O2 and Fe2+ in Hb decomposing H2O2 into •OH. The combination of •OH and SS adjuvant can improve tumor immunogenicity and activate immune system. Meanwhile, JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response. In this manner, SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis. To summarize, the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.
{"title":"A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment","authors":"Cuixia Zheng , Lingling Sun , Hongjuan Zhao , Mengya Niu , Dandan Zhang , Xinxin Liu , Qingling Song , Weijie Zhong , Baojin Wang , Yun Zhang , Lei Wang","doi":"10.1016/j.ajps.2024.100912","DOIUrl":"10.1016/j.ajps.2024.100912","url":null,"abstract":"<div><p>Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer. However, the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations. Furthermore, monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors. In this study, based on our discovery that spore shell (SS) of <em>Bacillus coagulans</em> exhibits excellent tumor-targeting ability and adjuvant activity, we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy, chemodynamic therapy and antitumor immunity for synergistic cancer treatment. In detail, SS is separated from probiotic spores and then attached to the surface of liposome (Lipo) that was loaded with hemoglobin (Hb), glucose oxidase (GOx) and JQ1 to construct SS@Lipo/Hb/GOx/JQ1. In tumor tissue, highly toxic hydroxyl radicals (•OH) are generated via sequential catalytic reactions: GOx catalyzing glucose into H<sub>2</sub>O<sub>2</sub> and Fe<sup>2+</sup> in Hb decomposing H<sub>2</sub>O<sub>2</sub> into •OH. The combination of •OH and SS adjuvant can improve tumor immunogenicity and activate immune system. Meanwhile, JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response. In this manner, SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis. To summarize, the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000291/pdfft?md5=6d76e9f0ffce2ff30af602552971af0c&pid=1-s2.0-S1818087624000291-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140785025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.ajps.2024.100923
Xilong Cui , Fanhui Liu , Shuang Cai , Tingting Wang , Sidi Zheng , Xinshu Zou , Linlin Wang , Siqi He , Yanhua Li , Zhiyun Zhang
The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-d-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of d-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An in vivo study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (P < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.
{"title":"Charge adaptive phytochemical-based nanoparticles for eradication of methicillin-resistant staphylococcus aureus biofilms","authors":"Xilong Cui , Fanhui Liu , Shuang Cai , Tingting Wang , Sidi Zheng , Xinshu Zou , Linlin Wang , Siqi He , Yanhua Li , Zhiyun Zhang","doi":"10.1016/j.ajps.2024.100923","DOIUrl":"10.1016/j.ajps.2024.100923","url":null,"abstract":"<div><p>The intrinsic resistance of MRSA coupled with biofilm antibiotic tolerance challenges the antibiotic treatment of MRSA biofilm infections. Phytochemical-based nanoplatform is a promising emerging approach for treatment of biofilm infection. However, their therapeutic efficacy was restricted by the low drug loading capacity and lack of selectivity. Herein, we constructed a surface charge adaptive phytochemical-based nanoparticle with high isoliquiritigenin (ISL) loading content for effective treatment of MRSA biofilm. A dimeric ISL prodrug (ISL-G2) bearing a lipase responsive ester bond was synthesized, and then encapsulated into the amphiphilic quaternized oligochitosan. The obtained ISL-G2 loaded NPs possessed positively charged surface, which allowed cis-aconityl-<span>d</span>-tyrosine (CA-Tyr) binding via electrostatic interaction to obtain ISL-G2@TMDCOS-Tyr NPs. The NPs maintained their negatively charged surface, thus prolonging the blood circulation time. In response to low pH in the biofilms, the fast removal of CA-Tyr led to a shift in their surface charge from negative to positive, which enhanced the accumulation and penetration of NPs in the biofilms. Sequentially, the pH-triggered release of <span>d</span>-tyrosine dispersed the biofilm and lipase-triggered released of ISL effectively kill biofilm MRSA. An <em>in vivo</em> study was performed on a MRSA biofilm infected wound model. This phytochemical-based system led to ∼2 log CFU (>99 %) reduction of biofilm MRSA as compared to untreated wound (<em>P</em> < 0.001) with negligible biotoxicity in mice. This phytochemical dimer nanoplatform shows great potential for long-term treatment of resistant bacterial infections.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000400/pdfft?md5=a8010c180b3afe2e2464817b9b8a723c&pid=1-s2.0-S1818087624000400-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140786781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition (DHC), which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies. Despite significant progress in reducing mortality rates from cardiovascular diseases (CVDs), heart failure remains a major cause of increased morbidity among diabetic patients. These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components, and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment. While a variety of conventional diagnostic and therapeutic strategies are available, DHC continues to present a significant challenge. Point-of-care diagnostics, supported by nanobiosensing techniques, offer a promising alternative for these complex scenarios. Although conventional medications have been widely used in DHC patients, they raise several concerns regarding various physiological aspects. Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC, offering a promising approach to deliver drugs beyond the limitations of traditional therapies. This article aims to explore the potential connections between autophagy, mitophagy and DHC, while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.
{"title":"Autophagy and mitophagy as potential therapeutic targets in diabetic heart condition: Harnessing the power of nanotheranostics","authors":"Sagnik Nag , Oishi Mitra , Bhanu Maturi , Simran Preet Kaur , Ankita Saini , Muskan Nama , Soumik Roy , Souvik Samanta , Leena Chacko , Rohan Dutta , Suresh Babu Sayana , Vetriselvan Subramaniyan , Jasvinder Singh Bhatti , Ramesh Kandimalla","doi":"10.1016/j.ajps.2024.100927","DOIUrl":"10.1016/j.ajps.2024.100927","url":null,"abstract":"<div><p>Autophagy and mitophagy pose unresolved challenges in understanding the pathology of diabetic heart condition (DHC), which encompasses a complex range of cardiovascular issues linked to diabetes and associated cardiomyopathies. Despite significant progress in reducing mortality rates from cardiovascular diseases (CVDs), heart failure remains a major cause of increased morbidity among diabetic patients. These cellular processes are essential for maintaining cellular balance and removing damaged or dysfunctional components, and their involvement in the development of diabetic heart disease makes them attractive targets for diagnosis and treatment. While a variety of conventional diagnostic and therapeutic strategies are available, DHC continues to present a significant challenge. Point-of-care diagnostics, supported by nanobiosensing techniques, offer a promising alternative for these complex scenarios. Although conventional medications have been widely used in DHC patients, they raise several concerns regarding various physiological aspects. Modern medicine places great emphasis on the application of nanotechnology to target autophagy and mitophagy in DHC, offering a promising approach to deliver drugs beyond the limitations of traditional therapies. This article aims to explore the potential connections between autophagy, mitophagy and DHC, while also discussing the promise of nanotechnology-based theranostic interventions that specifically target these molecular pathways.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000448/pdfft?md5=8e1fdf35ae6e7c29e70276be30b2b0c7&pid=1-s2.0-S1818087624000448-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141140621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.ajps.2024.100925
Xianglei Fu , Yanbin Shi , Zili Gu , Hengchang Zang , Lian Li , Qingjie Wang , Yongjun Wang , Xiaogang Zhao , Hang Wu , Shengnan Qiu , Yankun Zhang , Jiamin Zhou , Xiangqin Chen , Hua Shen , Guimei Lin
Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG. Once applied, MSLs strongly downregulated STAT3 expression in the tumor microenvironment, resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype. Meanwhile, the release of lidocaine hydrochloride (LID) was beneficial for pain relief and natural killer cell activation. Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life, including reduced MPE volume and pain relief in orthotopic NSCLC mouse models, even with a single administration. MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC, and may alter the treatment paradigms for other cancers.
{"title":"Immunotherapeutic hydrogel for co-delivery of STAT3 siRNA liposomes and lidocaine hydrochloride for postoperative comprehensive management of NSCLC in a single application","authors":"Xianglei Fu , Yanbin Shi , Zili Gu , Hengchang Zang , Lian Li , Qingjie Wang , Yongjun Wang , Xiaogang Zhao , Hang Wu , Shengnan Qiu , Yankun Zhang , Jiamin Zhou , Xiangqin Chen , Hua Shen , Guimei Lin","doi":"10.1016/j.ajps.2024.100925","DOIUrl":"10.1016/j.ajps.2024.100925","url":null,"abstract":"<div><p>Despite standard treatment for non-small cell lung cancer (NSCLC) being surgical resection, cancer recurrence and complications, such as induction of malignant pleural effusion (MPE) and significant postoperative pain, usually result in treatment failure. In this study, an alginate-based hybrid hydrogel (SOG) is developed that can be injected into the resection surface of the lungs during surgery. Briefly, endoplasmic reticulum-modified liposomes (MSLs) pre-loaded with the signal transducer and activator of transcription 3 (STAT3) small interfering RNA and lidocaine hydrochloride are encapsulated in SOG. Once applied, MSLs strongly downregulated STAT3 expression in the tumor microenvironment, resulting in the apoptosis of lung cancer cells and polarization of tumor-associated macrophages towards the M1-like phenotype. Meanwhile, the release of lidocaine hydrochloride (LID) was beneficial for pain relief and natural killer cell activation. Our data demonstrated MSL@LID@SOG not only efficiently inhibited tumor growth but also potently improved the quality of life, including reduced MPE volume and pain relief in orthotopic NSCLC mouse models, even with a single administration. MSL@LID@SOG shows potential for comprehensive clinical management upon tumor resection in NSCLC, and may alter the treatment paradigms for other cancers.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000424/pdfft?md5=af9866fa79376685878ba98645ec3d3b&pid=1-s2.0-S1818087624000424-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140932646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.ajps.2024.100924
Ming Zhou , Xiaoqin Yin , Bei Chen , Shuo Hu , Wenhu Zhou
Polyamine metabolism dysregulation is a hallmark of many cancers, offering a promising avenue for early tumor theranostics. This study presents the development of a nuclear probe derived from spermidine (SPM) for dual-purpose tumor PET imaging and internal radiation therapy. The probe, radiolabeled with either [68Ga]Ga for diagnostic applications or [177Lu]Lu for therapeutic use, was synthesized with exceptional purity, stability, and specific activity. Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells, showcasing outstanding tumor localization and target-to-non-target ratio. Mechanistic investigations employing polyamines, non-labeled precursor, and polyamine transport system (PTS) inhibitor, consistently affirmed the probeʼs targetability through recognition of the PTS. Notably, while previous reports indicated PTS upregulation in various tumor types for targeted therapy, this study observed no positive signals, highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis. Furthermore, when labeled with [177Lu], the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival. Investigations into biodistribution, excretion, and biosafety in healthy humans laid a robust foundation for clinical translation. This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics, offering promising prospects for clinical implementation.
{"title":"A PET probe targeting polyamine transport system for precise tumor diagnosis and therapy","authors":"Ming Zhou , Xiaoqin Yin , Bei Chen , Shuo Hu , Wenhu Zhou","doi":"10.1016/j.ajps.2024.100924","DOIUrl":"10.1016/j.ajps.2024.100924","url":null,"abstract":"<div><p>Polyamine metabolism dysregulation is a hallmark of many cancers, offering a promising avenue for early tumor theranostics. This study presents the development of a nuclear probe derived from spermidine (SPM) for dual-purpose tumor PET imaging and internal radiation therapy. The probe, radiolabeled with either [<sup>68</sup>Ga]Ga for diagnostic applications or [<sup>177</sup>Lu]Lu for therapeutic use, was synthesized with exceptional purity, stability, and specific activity. Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells, showcasing outstanding tumor localization and target-to-non-target ratio. Mechanistic investigations employing polyamines, non-labeled precursor, and polyamine transport system (PTS) inhibitor, consistently affirmed the probeʼs targetability through recognition of the PTS. Notably, while previous reports indicated PTS upregulation in various tumor types for targeted therapy, this study observed no positive signals, highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis. Furthermore, when labeled with [<sup>177</sup>Lu], the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival. Investigations into biodistribution, excretion, and biosafety in healthy humans laid a robust foundation for clinical translation. This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics, offering promising prospects for clinical implementation.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000412/pdfft?md5=157f1e7aca3e72950e4a7d25d1af5d05&pid=1-s2.0-S1818087624000412-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140756333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.ajps.2024.100928
Zhining Ma , Yuequan Wang , Huiyang He , Tong Liu , Qikun Jiang , Xiaohong Hou
Flurbiprofen (FB), a nonsteroidal anti-inflammatory drug, is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects. However, the racemic nature of its commercially available formulation (Ocufen®) limits the full potential of its therapeutic activity, as the (S)-enantiomer is responsible for the desired anti-inflammatory effects. Additionally, the limited corneal permeability of FB significantly restricts its bioavailability. In this study, we successfully separated the chiral isomers of FB to obtain the highly active (S)-FB. Subsequently, utilizing ion-pairing technology, we coupled (S)-FB with various counter-ions, such as sodium, diethylamine, trimethamine (TMA), and l-arginine, to enhance its ocular bioavailability. A comprehensive evaluation encompassed balanced solubility, octanol-water partition coefficient, corneal permeability, ocular pharmacokinetics, tissue distribution, and in vivo ocular anti-inflammatory activity of each chiral isomer salt. Among the various formulations, S-FBTMA exhibited superior water solubility (about 1–12 mg/ml), lipid solubility (1< lg Pow < 3) and corneal permeability. In comparison to Ocufen®, S-FBTMA demonstrated significantly higher in vivo anti-inflammatory activity and lower ocular irritability (such as conjunctival congestion and tingling). The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.
{"title":"Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies","authors":"Zhining Ma , Yuequan Wang , Huiyang He , Tong Liu , Qikun Jiang , Xiaohong Hou","doi":"10.1016/j.ajps.2024.100928","DOIUrl":"10.1016/j.ajps.2024.100928","url":null,"abstract":"<div><p>Flurbiprofen (FB), a nonsteroidal anti-inflammatory drug, is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects. However, the racemic nature of its commercially available formulation (Ocufen®) limits the full potential of its therapeutic activity, as the (<em>S</em>)-enantiomer is responsible for the desired anti-inflammatory effects. Additionally, the limited corneal permeability of FB significantly restricts its bioavailability. In this study, we successfully separated the chiral isomers of FB to obtain the highly active (<em>S</em>)-FB. Subsequently, utilizing ion-pairing technology, we coupled (<em>S</em>)-FB with various counter-ions, such as sodium, diethylamine, trimethamine (TMA), and l-arginine, to enhance its ocular bioavailability. A comprehensive evaluation encompassed balanced solubility, octanol-water partition coefficient, corneal permeability, ocular pharmacokinetics, tissue distribution, and <em>in vivo</em> ocular anti-inflammatory activity of each chiral isomer salt. Among the various formulations, S-FBTMA exhibited superior water solubility (about 1–12 mg/ml), lipid solubility (1< lg P<sub>ow</sub> < 3) and corneal permeability. In comparison to Ocufen®, S-FBTMA demonstrated significantly higher <em>in vivo</em> anti-inflammatory activity and lower ocular irritability (such as conjunctival congestion and tingling). The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S181808762400045X/pdfft?md5=d713cf3b9937b0a72348e2d4c6af4318&pid=1-s2.0-S181808762400045X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141139770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.ajps.2024.100913
Rui Wang , Tongyao Liu , Xinhong Li , Enhao Lu , Yiting Chen , Kuankuan Luo , Tao Wang , Xueli Huang , Zhiwen Zhang , Shilin Du , Xianyi Sha
Flare and multiple recurrences pose significant challenges in gouty arthritis. Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences. It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis, calling for therapeutic systems to achieve these two goals simultaneously. In this study, we propose a biomimetic integrated nanozyme, HMPB-Pt@MM, comprising platinum nanozyme and hollow Prussian blue. It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages. Additionally, it rapidly targets inflamed ankles through the camouflage of macrophage membranes. Furthermore, HMPB-Pt@MM exhibits urate oxidase-like capabilities, continuously metabolizing locally elevated uric acid concentrations, ultimately inhibiting multiple recurrences of gouty arthritis. In summary, HMPB-Pt@MM integrates ROS clearance with uric acid metabolism, offering a promising platform for the treatment of gouty arthritis.
{"title":"Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis","authors":"Rui Wang , Tongyao Liu , Xinhong Li , Enhao Lu , Yiting Chen , Kuankuan Luo , Tao Wang , Xueli Huang , Zhiwen Zhang , Shilin Du , Xianyi Sha","doi":"10.1016/j.ajps.2024.100913","DOIUrl":"10.1016/j.ajps.2024.100913","url":null,"abstract":"<div><p>Flare and multiple recurrences pose significant challenges in gouty arthritis. Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences. It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis, calling for therapeutic systems to achieve these two goals simultaneously. In this study, we propose a biomimetic integrated nanozyme, HMPB-Pt@MM, comprising platinum nanozyme and hollow Prussian blue. It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages. Additionally, it rapidly targets inflamed ankles through the camouflage of macrophage membranes. Furthermore, HMPB-Pt@MM exhibits urate oxidase-like capabilities, continuously metabolizing locally elevated uric acid concentrations, ultimately inhibiting multiple recurrences of gouty arthritis. In summary, HMPB-Pt@MM integrates ROS clearance with uric acid metabolism, offering a promising platform for the treatment of gouty arthritis.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000308/pdfft?md5=ae817b13af18eab2a96c3b71ceede50d&pid=1-s2.0-S1818087624000308-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140788973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1016/j.ajps.2024.100922
Hongbing Liu , Muse Ji , Peifu Xiao , Jingxin Gou , Tian Yin , Haibing He , Xing Tang , Yu Zhang
Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract. These notorious side effects seriously compromise patients' quality of life, especially in patients with chronic diseases. Therefore, glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention. Among them, prodrugs have the advantages of low investment, low risk, and high success rate, making them a promising strategy. In this review, we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades, including polymer-based prodrugs, dendrimer-based prodrugs, antibody-drug conjugates, peptide-drug conjugates, carbohydrate-based prodrugs, aliphatic acid-based prodrugs and so on. Besides, we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs. This review is expected to be helpful for the research and development of novel GCs and prodrugs.
{"title":"Glucocorticoids-based prodrug design: Current strategies and research progress","authors":"Hongbing Liu , Muse Ji , Peifu Xiao , Jingxin Gou , Tian Yin , Haibing He , Xing Tang , Yu Zhang","doi":"10.1016/j.ajps.2024.100922","DOIUrl":"10.1016/j.ajps.2024.100922","url":null,"abstract":"<div><p>Attributing to their broad pharmacological effects encompassing anti-inflammation, antitoxin, and immunosuppression, glucocorticoids (GCs) are extensively utilized in the clinic for the treatment of diverse diseases such as lupus erythematosus, nephritis, arthritis, ulcerative colitis, asthma, keratitis, macular edema, and leukemia. However, long-term use often causes undesirable side effects, including metabolic disorders-induced Cushing's syndrome (buffalo back, full moon face, hyperglycemia, etc.), osteoporosis, aggravated infection, psychosis, glaucoma, and cataract. These notorious side effects seriously compromise patients' quality of life, especially in patients with chronic diseases. Therefore, glucocorticoid-based advanced drug delivery systems for reducing adverse effects have received extensive attention. Among them, prodrugs have the advantages of low investment, low risk, and high success rate, making them a promising strategy. In this review, we propose the strategies for the design and summarize current research progress of glucocorticoid-based prodrugs in recent decades, including polymer-based prodrugs, dendrimer-based prodrugs, antibody-drug conjugates, peptide-drug conjugates, carbohydrate-based prodrugs, aliphatic acid-based prodrugs and so on. Besides, we also raise issues that need to be focused on during the development of glucocorticoid-based prodrugs. This review is expected to be helpful for the research and development of novel GCs and prodrugs.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":10.2,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000394/pdfft?md5=1a86498bf675c0b810b1b5ce25a9df62&pid=1-s2.0-S1818087624000394-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140781057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}