Asian Journal of Pharmaceutical Sciences最新文献

{"title":"MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation","authors":"Wenyi Chen ,&nbsp;Feiyan Lin ,&nbsp;Xudong Feng ,&nbsp;Qigu Yao ,&nbsp;Yingduo Yu ,&nbsp;Feiqiong Gao ,&nbsp;Jiahang Zhou ,&nbsp;Qiaoling Pan ,&nbsp;Jian Wu ,&nbsp;Jinfeng Yang ,&nbsp;Jiong Yu ,&nbsp;Hongcui Cao ,&nbsp;Lanjuan Li","doi":"10.1016/j.ajps.2024.100889","DOIUrl":"10.1016/j.ajps.2024.100889","url":null,"abstract":"<div><p>Primary sclerosing cholangitis (PSC) is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis, with no curative treatment available, and liver transplantation is inevitable for end-stage patients. Human placental mesenchymal stem cell (hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis, inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease. Here, we prepared hpMSC-derived exosomes (Exo^MSC) and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^−/− mice and multicellular organoids established from PSC patients. The results showed that Exo^MSC ameliorated liver fibrosis in Mdr2^−/− mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis, and the percentage of CD4⁺IL-17A⁺T cells was reduced both in Exo^MSC-treated Mdr2^−/− mice (Mdr2^−/−-Exo) in vivo and Exo^MSC-treated Th17 differentiation progressed in vitro. Furthermore, Exo^MSC improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids. Thus, our data demonstrate the anti-fibrosis effect of Exo^MSC in PSC disease by inhibiting Th17 differentiation, and ameliorating the Th17-induced microenvironment, indicating the promising potential therapeutic role of Exo^MSC in liver fibrosis of PSC or Th17-related diseases.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 1","pages":"Article 100889"},"PeriodicalIF":10.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000060/pdfft?md5=a4ded8e46a53f0c04514f317a5f74cbb&pid=1-s2.0-S1818087624000060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139826776","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}

{"title":"Synergistic chemotherapy/PTT/oxygen enrichment by multifunctional liposomal polydopamine nanoparticles for rheumatoid arthritis treatment","authors":"Xiaoling Fu ,&nbsp;Yutong Song ,&nbsp;Xianquan Feng ,&nbsp;Zhihong Liu ,&nbsp;Wenhao Gao ,&nbsp;Hongtao Song ,&nbsp;Qian Zhang","doi":"10.1016/j.ajps.2024.100885","DOIUrl":"10.1016/j.ajps.2024.100885","url":null,"abstract":"<div><p>Amultifunctional liposomal polydopamine nanoparticle (MPM@Lipo) was designed in this study, to combine chemotherapy, photothermal therapy (PTT) and oxygen enrichment to clear hyperproliferating inflammatory cells and improve the hypoxic microenvironment for rheumatoid arthritis (RA) treatment. MPM@Lipo significantly scavenged intracellular reactive oxygen species and relieved joint hypoxia, thus contributing to the repolarization of M1 macrophages into M2 phenotype. Furthermore, MPM@Lipo could accumulate at inflammatory joints, inhibit the production of inflammatory factors, and protect cartilage <em>in vivo</em>, effectively alleviating RA progression in a rat adjuvant-induced arthritis model. Moreover, upon laser irradiation, MPM@Lipo can elevate the temperature to not only significantly obliterate excessively proliferating inflammatory cells but also accelerate the production of methotrexate and oxygen, resulting in excellent RA treatment effects. Overall, the use of synergistic chemotherapy/PTT/oxygen enrichment therapy to treat RA is a powerful potential strategy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 1","pages":"Article 100885"},"PeriodicalIF":10.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087624000023/pdfft?md5=7413ccd92bfd57765612c4af7cfb3dd9&pid=1-s2.0-S1818087624000023-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139773562","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}

{"title":"Stem cell-based ischemic stroke therapy: Novel modifications and clinical challenges","authors":"Yuankai Sun ,&nbsp;Xinchi Jiang ,&nbsp;Jianqing Gao","doi":"10.1016/j.ajps.2023.100867","DOIUrl":"10.1016/j.ajps.2023.100867","url":null,"abstract":"<div><p>Ischemic stroke (IS) causes severe disability and high mortality worldwide. Stem cell (SC) therapy exhibits unique therapeutic potential for IS that differs from current treatments. SC's cell homing, differentiation and paracrine abilities give hope for neuroprotection. Recent studies on SC modification have enhanced therapeutic effects for IS, including gene transfection, nanoparticle modification, biomaterial modification and pretreatment. These methods improve survival rate, homing, neural differentiation, and paracrine abilities in ischemic areas. However, many problems must be resolved before SC therapy can be clinically applied. These issues include production quality and quantity, stability during transportation and storage, as well as usage regulations. Herein, we reviewed the brief pathogenesis of IS, the “multi-mechanism” advantages of SCs for treating IS, various SC modification methods, and SC therapy challenges. We aim to uncover the potential and overcome the challenges of using SCs for treating IS and convey innovative ideas for modifying SCs.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"19 1","pages":"Article 100867"},"PeriodicalIF":10.2,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623000946/pdfft?md5=e16f196e132a1bd840c5bc7a8fb03fa9&pid=1-s2.0-S1818087623000946-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135614303","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}

{"title":"Smart stimuli-responsive drug delivery systems in spotlight of COVID-19","authors":"Zeinab Najjari,&nbsp;Farzaneh Sadri,&nbsp;Jaleh Varshosaz","doi":"10.1016/j.ajps.2023.100873","DOIUrl":"10.1016/j.ajps.2023.100873","url":null,"abstract":"<div><p>The world has been dealing with a novel severe acute respiratory syndrome (SARS-CoV-2) since the end of 2019, which threatens the lives of many people worldwide. COVID-19 causes respiratory infection with different symptoms, from sneezing and coughing to pneumonia and sometimes gastric symptoms. Researchers worldwide are actively developing novel drug delivery systems (DDSs), such as stimuli-responsive DDSs. The ability of these carriers to respond to external/internal and even multiple stimuli is essential in creating \"smart\" DDS that can effectively control dosage, sustained release, individual variations, and targeted delivery. To conduct a comprehensive literature survey for this article, the terms “Stimuli-responsive”, “COVID-19″ and “Drug delivery” were searched on databases/search engines like “Google Scholar”, “NCBI”, “PubMed”, and “Science Direct”. Many different types of DDSs have been proposed, including those responsive to various exogenous (light, heat, ultrasound and magnetic field) or endogenous (microenvironmental changes in pH, ROS and enzymes) stimuli. Despite significant progress in DDS research, several challenging issues must be addressed to fill the gaps in the literature. Therefore, this study reviews the drug release mechanisms and applications of endogenous/exogenous stimuli-responsive DDSs while also exploring their potential with respect to COVID-19.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 6","pages":"Article 100873"},"PeriodicalIF":10.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623000983/pdfft?md5=2def410ea2763914f9352411b7f49896&pid=1-s2.0-S1818087623000983-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544266","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}

{"title":"CRISPR/Cas9 systems: Delivery technologies and biomedical applications","authors":"Yimin Du ,&nbsp;Yanfei Liu ,&nbsp;Jiaxin Hu ,&nbsp;Xingxing Peng ,&nbsp;Zhenbao Liu","doi":"10.1016/j.ajps.2023.100854","DOIUrl":"10.1016/j.ajps.2023.100854","url":null,"abstract":"<div><p>The emergence of the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome-editing system has brought about a significant revolution in the realm of managing human diseases, establishing animal models, and so on. To fully harness the potential of this potent gene-editing tool, ensuring efficient and secure delivery to the target site is paramount. Consequently, developing effective delivery methods for the CRISPR/Cas9 system has become a critical area of research. In this review, we present a comprehensive outline of delivery strategies and discuss their biomedical applications in the CRISPR/Cas9 system. We also provide an in-depth analysis of physical, viral vector, and non-viral vector delivery strategies, including plasmid-, mRNA- and protein-based approach. In addition, we illustrate the biomedical applications of the CRISPR/Cas9 system. This review highlights the key factors affecting the delivery process and the current challenges facing the CRISPR/Cas9 system, while also delineating future directions and prospects that could inspire innovative delivery strategies. This review aims to provide new insights and ideas for advancing CRISPR/Cas9-based delivery strategies and to facilitate breakthroughs in biomedical research and therapeutic applications.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 6","pages":"Article 100854"},"PeriodicalIF":10.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623000818/pdfft?md5=2014e53ae0ae096387ebc845aee275aa&pid=1-s2.0-S1818087623000818-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009403","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}

{"title":"Exploring the potential to enhance drug distribution in the brain subregion via intranasal delivery of nanoemulsion in combination with borneol as a guider","authors":"Xin Shen,&nbsp;Zhixiang Cui,&nbsp;Yidan Wei,&nbsp;Yingnan Huo,&nbsp;Duo Yu,&nbsp;Xin Zhang,&nbsp;Shirui Mao","doi":"10.1016/j.ajps.2023.100778","DOIUrl":"10.1016/j.ajps.2023.100778","url":null,"abstract":"<div><p>The number of people with Alzheimer's disease (AD) is increasing annually, with the nidus mainly concentrated in the cortex and hippocampus. Despite of numerous efforts, effective treatment of AD is still facing great challenges due to the blood brain barrier (BBB) and limited drug distribution in the AD nidus sites. Thus, in this study, using vinpocetine (VIN) as a model drug, the objective is to explore the feasibility of tackling the above bottleneck via intranasal drug delivery in combination with a brain guider, borneol (BOR), using nanoemulsion (NE) as the carrier. First of all, the NE were prepared and characterized. <em>In vivo</em> behavior of the NE after intranasal administration was investigated. Influence of BOR dose, BOR administration route on drug brain targeting behavior was evaluated, and the influence of BOR addition on drug brain subregion distribution was probed. It was demonstrated that all the NE had comparable size and similar retention behavior after intranasal delivery. Compared to intravenous injection, improved brain targeting effect was observed by intranasal route, and drug targeting index (DTI) of the VIN<img>NE group was 154.1%, with the nose-to-brain direct transport percentage (DTP) 35.1%. Especially, remarkably enhanced brain distribution was achieved after BOR addition in the NE, with the extent depending on BOR dose. VIN brain concentration was the highest in the VIN-1-BOR-NE group at BOR dose of 1 mg/kg, with the DTI reaching 596.1% and the DTP increased to 83.1%. BOR could exert better nose to brain delivery when administrated together with the drug via intranasal route. Notably, BOR can remarkably enhance drug distribution in both hippocampus and cortex, the nidus areas of AD. In conclusion, in combination with intranasal delivery and the intrinsic brain guiding effect of BOR, drug distribution not only in the brain but also in the cortex and hippocampus can be enhanced significantly, providing the perquisite for improved therapeutic efficacy of AD.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 6","pages":"Article 100778"},"PeriodicalIF":10.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623000053/pdfft?md5=fdfef7004cd591260130e55c5f7829e5&pid=1-s2.0-S1818087623000053-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49242097","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}

{"title":"Engineered exosomes-based theranostic strategy for tumor metastasis and recurrence","authors":"Min Deng ,&nbsp;Shuang Wu ,&nbsp;Peizheng Huang ,&nbsp;Yun Liu ,&nbsp;Chong Li ,&nbsp;Ji Zheng","doi":"10.1016/j.ajps.2023.100870","DOIUrl":"10.1016/j.ajps.2023.100870","url":null,"abstract":"<div><p>Metastasis-associated processes are the predominant instigator of fatalities linked to cancer, wherein the pivotal role of circulating tumor cells lies in the resurgence of malignant growth. In recent epochs, exosomes, constituents of the extracellular vesicle cohort, have garnered attention within the field of tumor theranostics owing to their inherent attributes encompassing biocompatibility, modifiability, payload capacity, stability, and therapeutic suitability. Nonetheless, the rudimentary functionalities and limited efficacy of unmodified exosomes curtail their prospective utility. In an effort to surmount these shortcomings, intricate methodologies amalgamating nanotechnology with genetic manipulation, chemotherapy, immunotherapy, and optical intervention present themselves as enhanced avenues to surveil and intercede in tumor metastasis and relapse. This review delves into the manifold techniques currently employed to engineer exosomes, with a specific focus on elucidating the interplay between exosomes and the metastatic cascade, alongside the implementation of tailored exosomes in abating tumor metastasis and recurrence. This review not only advances comprehension of the evolving landscape within this domain but also steers the trajectory of forthcoming investigations.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 6","pages":"Article 100870"},"PeriodicalIF":10.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623000971/pdfft?md5=66062094b1be145e4db99ecf53ffa7c6&pid=1-s2.0-S1818087623000971-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544265","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}

{"title":"Mechanistic engineering of celastrol liposomes induces ferroptosis and apoptosis by directly targeting VDAC2 in hepatocellular carcinoma","authors":"Piao Luo ,&nbsp;Qian Zhang ,&nbsp;Shuo Shen ,&nbsp;Yehai An ,&nbsp;Lixia Yuan ,&nbsp;Yin-Kwan Wong ,&nbsp;Sizhe Huang ,&nbsp;Shaohui Huang ,&nbsp;Jingnan Huang ,&nbsp;Guangqing Cheng ,&nbsp;Jiahang Tian ,&nbsp;Yu Chen ,&nbsp;Xiaoyong Zhang ,&nbsp;Weiguang Li ,&nbsp;Songqi He ,&nbsp;Jigang Wang ,&nbsp;Qingfeng Du","doi":"10.1016/j.ajps.2023.100874","DOIUrl":"10.1016/j.ajps.2023.100874","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) is one of most common and deadliest malignancies. Celastrol (Cel), a natural product derived from the <em>Tripterygium wilfordii</em> plant, has been extensively researched for its potential effectiveness in fighting cancer. However, its clinical application has been hindered by the unclear mechanism of action. Here, we used chemical proteomics to identify the direct targets of Cel and enhanced its targetability and anti-tumor capacity by developing a Cel-based liposomes in HCC. We demonstrated that Cel selectively targets the voltage-dependent anion channel 2 (VDAC2). Cel directly binds to the cysteine residues of VDAC2, and induces cytochrome C release via dysregulating VDAC2-mediated mitochondrial permeability transition pore (mPTP) function. We further found that Cel induces ROS-mediated ferroptosis and apoptosis in HCC cells. Moreover, coencapsulation of Cel into alkyl glucoside-modified liposomes (AGCL) improved its antitumor efficacy and minimized its side effects. AGCL has been shown to effectively suppress the proliferation of tumor cells. In a xenograft nude mice experiment, AGCL significantly inhibited tumor growth and promoted apoptosis. Our findings reveal that Cel directly targets VDAC2 to induce mitochondria-dependent cell death, while the Cel liposomes enhance its targetability and reduces side effects. Overall, Cel shows promise as a therapeutic agent for HCC.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 6","pages":"Article 100874"},"PeriodicalIF":10.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623001009/pdfft?md5=e8710b9808d908f1af5d0d3686da10d9&pid=1-s2.0-S1818087623001009-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544268","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}

{"title":"A nanocomposite competent to overcome cascade drug resistance in ovarian cancer via mitochondria dysfunction and NO gas synergistic therapy","authors":"Min Zhong ,&nbsp;Peiqin Liang ,&nbsp;Zhenzhen Feng ,&nbsp;Xin Yang ,&nbsp;Guang Li ,&nbsp;Rui Sun ,&nbsp;Lijuan He ,&nbsp;Jinxiu Tan ,&nbsp;Yangpengcheng Xiao ,&nbsp;Zhiqiang Yu ,&nbsp;Muhua Yi ,&nbsp;Xuefeng Wang","doi":"10.1016/j.ajps.2023.100872","DOIUrl":"10.1016/j.ajps.2023.100872","url":null,"abstract":"<div><p>Ovarian cancer (OC) is one of the most common and recurring malignancies in gynecology. Patients with relapsed OC always develop \"cascade drug resistance\" (CDR) under repeated chemotherapy, leading to subsequent failure of chemotherapy. To overcome this challenge, amphiphiles (P1) carrying a nitric oxide (NO) donor (Isosorbide 5-mononitrate, ISMN) and high-density disulfide are synthesized for encapsulating mitochondria-targeted tetravalent platinum prodrug (TPt) to construct a nanocomposite (INP@TPt). Mechanism studies indicated that INP@TPt significantly inhibited drug-resistant cells by increasing cellular uptake and mitochondrial accumulation of platinum, depleting glutathione, and preventing apoptosis escape through generating highly toxic peroxynitrite anion (ONOO⁻). To better replicate the microenvironmental and histological characteristics of the drug resistant primary tumor, an OC patient-derived tumor xenograft (PDX^OC) model in BALB/c nude mice was established. INP@TPt showed the best therapeutic effects in the PDX^OC model. The corresponding tumor tissues contained high ONOO⁻ levels, which were attributed to the simultaneous release of O₂^•− and NO in tumor tissues. Taken together, INP@TPt-based systematic strategy showed considerable potential and satisfactory biocompatibility in overcoming platinum CDR, providing practical applications for ovarian therapy.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 6","pages":"Article 100872"},"PeriodicalIF":10.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623000995/pdfft?md5=30c6f2eb359f6cf77d74454842fadb5a&pid=1-s2.0-S1818087623000995-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138544267","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}

{"title":"Preliminary delivery efficiency prediction of nanotherapeutics into crucial cell populations in bone marrow niche","authors":"Huijuan Chen ,&nbsp;Anzhi Hu ,&nbsp;Mengdi Xiao ,&nbsp;Shiyi Hong ,&nbsp;Jing Liang ,&nbsp;Quanlong Zhang ,&nbsp;Yang Xiong ,&nbsp;Mancang Gu ,&nbsp;Chaofeng Mu","doi":"10.1016/j.ajps.2023.100868","DOIUrl":"https://doi.org/10.1016/j.ajps.2023.100868","url":null,"abstract":"<div><p>Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches. Precise regulation of these cell types can remodel niches and develop new therapeutics. Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively. However, the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown, and there is no method available for predicting delivery efficiency in these cell types. Here, we constructed a three-dimensional bone marrow niche composed of three crucial cell populations: endothelial cells (ECs), mesenchymal stromal cells (MSCs), and osteoblasts (OBs). Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs <em>in vitro</em>. Less than 5% of nanocarriers were taken up by three stromal cell types, and most of them were located in the extracellular matrix. Delivery efficiency in sinusoidal ECs, arteriole ECs, MSCs, and OBs <em>in vivo</em> was analyzed. The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types <em>in vitro</em> is positively linear correlated with its delivery efficiency <em>in vivo</em>. The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs, no matter what kind of nanocarrier. The overall efficiency into sinusoidal ECs was greatly lower than that into arteriole ECs. All nanocarriers were hard to be delivered into OBs (&lt;1%). Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments <em>in vivo</em> could be predicted via detecting their cellular uptake in bone marrow niches <em>in vitro</em>. This study provided the methodology for niche-directed nanotherapeutics development.</p></div>","PeriodicalId":8539,"journal":{"name":"Asian Journal of Pharmaceutical Sciences","volume":"18 6","pages":"Article 100868"},"PeriodicalIF":10.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1818087623000958/pdfft?md5=f4cece5032301d1afb7e61a982d78a22&pid=1-s2.0-S1818087623000958-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138472249","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}