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A natural compound-empowered podophyllotoxin prodrug nanoassembly magnifies efficacy-toxicity benefits in cancer chemotherapy 一种由天然化合物赋能的荚叶毒素原药纳米组合可放大癌症化疗的疗效和毒性优势
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100892

Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery. However, prodrug activation remains a rate-limiting step for exerting therapeutic actions, which requires to quickly reach the minimum valid concentrations of free drugs. Fortunately, we find that a natural compound (BL-193) selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin (PPT) at ineffective dose concentrations. Based on this, we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT. Specifically, a redox-sensitive prodrug (PSSF) of PPT is synthesized by coupling 9-fluorenyl-methanol (Fmoc-OH) with PPT linked via disulfide bond. Intriguingly, PSSF with a π-conjugated structure readily co-assembles with BL-193 into stable nanoassembly. Significantly, BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic window for PPT. Moreover, prodrug design and precise hybrid nanoassembly well manage off-target toxicity. As expected, such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses. This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.

小分子原药纳米组装技术在减少脱靶毒性方面具有独特优势,已被广泛应用于抗肿瘤给药。然而,原药活化仍然是发挥治疗作用的一个限制性步骤,需要快速达到游离药物的最低有效浓度。幸运的是,我们发现一种天然化合物(BL-193)能在无效剂量浓度下选择性地提高乳腺癌细胞对豆荚毒素(PPT)的化疗敏感性。在此基础上,我们提出将原药纳米组装与化疗增敏相结合,以充分释放 PPT 的化疗潜力。具体来说,我们将 9-芴基甲醇(Fmoc-OH)与通过二硫键连接的 PPT 结合在一起,合成了 PPT 的氧化还原敏感原药(PSSF)。有趣的是,具有 π 共轭结构的 PSSF 很容易与 BL-193 共同组装成稳定的纳米组件。值得注意的是,BL-193 是一种出色的化疗增敏剂,为 PPT 创造了一个超低剂量化疗窗口。此外,原药设计和精确的混合纳米组装可以很好地控制脱靶毒性。正如预期的那样,这种由 BL-193 赋能的原药纳米组合能激发有效的抗肿瘤反应。这项研究为放大化疗疗效-毒性效益提供了一种新的范例。
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引用次数: 0
Design strategies, advances and future perspectives of colon-targeted delivery systems for the treatment of inflammatory bowel disease 治疗炎症性肠病的结肠靶向给药系统的设计策略、进展和未来展望
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100943

Inflammatory bowel diseases (IBD) significantly contribute to high mortality globally and negatively affect patients' qualifications of life. The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations. Moreover, certain natural or synthetic anti-inflammatory drugs are associated with poor targeting, low drug accumulation at the lesion site, and other side effects, hindering them from exerting their therapeutic effects. Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment. This review mainly discusses the treatment status of IBD, obstacles to drug delivery, design strategies of colon-targeted delivery systems, and perspectives on the existing complementary therapies. Moreover, based on recent reports, we summarized the therapeutic mechanism of colon-targeted drug delivery. Finally, we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy.

炎症性肠病(IBD)是导致全球高死亡率的重要原因,并对患者的生活质量造成负面影响。胃肠道具有独特的解剖特点和生理环境限制。此外,某些天然或合成抗炎药物的靶向性差、在病变部位的药物蓄积量低以及其他副作用,也阻碍了它们发挥治疗效果。结肠靶向给药系统是治疗 IBD 的新型载体,具有很强的吸引力。这篇综述主要讨论了 IBD 的治疗现状、给药障碍、结肠靶向给药系统的设计策略以及对现有辅助疗法的展望。此外,根据最新报道,我们总结了结肠靶向给药的治疗机制。最后,我们探讨了促进利用先进纳米药物治疗 IBD 的挑战和未来方向。
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引用次数: 0
Antibiotic-loaded lactoferrin nanoparticles as a platform for enhanced infection therapy through targeted elimination of intracellular bacteria 抗生素负载的乳铁蛋白纳米颗粒是通过靶向消除细胞内细菌来加强感染治疗的平台
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100926

Intracellular bacteria can multiply inside host cells and manipulate their biology, and the efficacy of traditional antibiotic drug therapy for intracellular bacteria is limited by inadequate drug accumulation. Fighting against these stealthy bacteria has been a long-standing challenge. Here, a system of stimuli-responsive lactoferrin (Lf) nanoparticles is prepared using protein self-assembly technology to deliver broad-spectrum antibiotic rifampicin (Rif) (Rif@Lf NPs) for enhanced infection therapy through targeted elimination of intracellular bacteria. Compared to Rif@BSA NPs, the Rif@Lf NPs can specifically target macrophages infected by bacteria, thus increasing the accumulation of Rif within macrophages. Subsequently, Rif@Lf NPs with positive surface charge further displayed targeted adherence to the bacteria within macrophages and released Rif rapidly in a redox-responsive manner. Combined with the antibacterial activities of Lf and Rif, the Rif@Lf NPs showed broad-spectrum antibiotic abilities to intracellular bacteria and biofilms. As a result, the Rif@Lf NPs with high safety exhibited excellent therapeutic efficacy in the disease models of subcutaneous infection, sepsis, and bacterial keratitis. Taken together, the antibiotic-loaded Lf nanoparticles present a promising platform to combat pathogen infections through targeted elimination of intracellular bacteria.

胞内细菌可以在宿主细胞内繁殖并操纵宿主细胞的生物学特性,而传统的抗生素药物疗法对胞内细菌的疗效因药物积累不足而受到限制。对付这些隐形细菌是一项长期的挑战。本文利用蛋白质自组装技术制备了一种刺激响应型乳铁蛋白(Lf)纳米粒子系统,可递送广谱抗生素利福平(Rif)(Rif@Lf NPs),通过靶向消灭细胞内细菌来增强感染治疗效果。与 Rif@BSA NPs 相比,Rif@Lf NPs 可特异性地靶向被细菌感染的巨噬细胞,从而增加 Rif 在巨噬细胞内的积累。随后,表面带正电荷的 Rif@Lf NPs 进一步显示出对巨噬细胞内细菌的靶向粘附性,并以氧化还原反应的方式快速释放 Rif。结合 Lf 和 Rif 的抗菌活性,Rif@Lf NPs 对细胞内细菌和生物膜具有广谱抗菌能力。因此,安全性高的 Rif@Lf NPs 在皮下注射感染、败血症和细菌性角膜炎等疾病模型中表现出卓越的疗效。综上所述,负载抗生素的 Lf 纳米粒子是通过有针对性地消灭细胞内细菌来抗击病原体感染的一个前景广阔的平台。
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引用次数: 0
Carrier-free cryptotanshinone-peptide conjugates self-assembled nanoparticles: An efficient and low-risk strategy for acne vulgaris 无载体隐丹参酮肽共轭物自组装纳米颗粒:治疗寻常痤疮的高效低风险策略
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100946

Acne vulgaris ranks as the second most prevalent dermatological condition worldwide, and there are still insufficient safe and reliable drugs to treat it. Cryptotanshinone (CTS), a bioactive compound derived from traditional Chinese medicine Salvia miltiorrhiza, has shown promise for treating acne vulgaris due to its broad-spectrum antimicrobial and significant anti-inflammatory properties. Nevertheless, its local application is hindered by its low solubility and poor skin permeability. To overcome these challenges, a carrier-free pure drug self-assembled nanosystem is employed, which can specifically modify drug molecules based on the disease type and microenvironment, offering a potential for more effective treatment. We designed and synthesized three distinct structures of cationic CTS-peptide conjugates, creating self-assembled nanoparticles. This study has explored their self-assembly behavior, skin permeation, cellular uptake, and both in vitro and in vivo anti-acne effects. Molecular dynamics simulations revealed these nanoparticles form through intermolecular hydrogen bonding and π-π stacking interactions. Notably, self-assembled nanoparticles demonstrated enhanced bioavailability with higher skin permeation and cellular uptake rates. Furthermore, the nanoparticles exhibited superior anti-acne effects compared to the parent drug, attributed to heightened antimicrobial activity and significant downregulation of the MAPK/NF-κB pathway, leading to reduced expression of pro-inflammatory factors including TNF-α, IL-1β and IL-8. In summary, the carrier-free self-assembled nanoparticles based on CTS-peptide conjugate effectively address the issue of poor skin bioavailability, offering a promising new approach for acne treatment.

寻常痤疮是全球第二大皮肤病,但目前仍没有足够安全可靠的药物来治疗它。隐丹参酮(CTS)是从传统中药丹参中提取的一种生物活性化合物,具有广谱抗菌和显著消炎的特性,有望治疗寻常型痤疮。然而,由于其溶解度低、皮肤渗透性差,其局部应用受到阻碍。为了克服这些挑战,我们采用了一种无载体的纯药物自组装纳米系统,它可以根据疾病类型和微环境对药物分子进行特异性修饰,为更有效的治疗提供了可能。我们设计并合成了三种不同结构的阳离子 CTS 肽共轭物,形成了自组装纳米粒子。这项研究探讨了它们的自组装行为、皮肤渗透、细胞摄取以及体内外抗痤疮效果。分子动力学模拟显示,这些纳米粒子是通过分子间氢键和π-π堆积相互作用形成的。值得注意的是,自组装的纳米颗粒具有更高的皮肤渗透率和细胞吸收率,从而提高了生物利用率。此外,与母体药物相比,纳米粒子还具有更优越的抗痤疮效果,这归功于其抗菌活性的增强以及对 MAPK/NF-κB通路的显著下调,从而减少了促炎因子(包括 TNF-α、IL-1β 和 IL-8)的表达。总之,基于 CTS 肽共轭物的无载体自组装纳米粒子有效地解决了皮肤生物利用度差的问题,为痤疮治疗提供了一种前景广阔的新方法。
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引用次数: 0
From mesenchymal stem cells to their extracellular vesicles: Progress and prospects for asthma therapy 从间充质干细胞到细胞外囊泡:哮喘治疗的进展与前景
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100942

Asthma is a widespread public health concern, with an increasing incidence. Despite the implementation of current treatment strategies, asthma control, particularly for severe cases, remains suboptimal. Recent research has revealed the encouraging prospects of extracellular vesicles (EVs) secreted by mesenchymal stem cells (MSCs) as a viable therapeutic option for alleviating asthma symptoms. Therefore, the present review aims to provide an overview of the current progress and the therapeutic mechanisms of using MSC-derived EVs (MSC-EVs) for asthma treatment. Additionally, different administration approaches for EVs and their impacts on biodistribution and the curative outcomes of EVs are summarized. Notably, the potential benefits of nebulized inhalation of MSC-EVs are addressed. Also, the possibilities and challenges of using MSC-EVs for asthma treatment in clinics are highlighted. Overall, this review is intended to give new insight into the utilization of MSC-EVs as a potential biological drug for asthma treatment.

哮喘是一个普遍的公共卫生问题,发病率不断上升。尽管实施了当前的治疗策略,但哮喘的控制率,尤其是对严重病例的控制率仍不理想。最近的研究显示,间充质干细胞(MSCs)分泌的细胞外囊泡(EVs)作为缓解哮喘症状的一种可行治疗方案,前景令人鼓舞。因此,本综述旨在概述利用间充质干细胞衍生的细胞外小泡(MSC-EVs)治疗哮喘的当前进展和治疗机制。此外,还总结了EVs的不同给药方法及其对生物分布和EVs治疗效果的影响。值得注意的是,本文探讨了雾化吸入间充质干细胞-EVs 的潜在益处。此外,还强调了在临床中使用间充质干细胞-EVs 治疗哮喘的可能性和挑战。总之,本综述旨在为利用间充质干细胞-EVs 作为治疗哮喘的潜在生物药物提供新的见解。
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引用次数: 0
Pulmonary fibroblast-specific delivery of siRNA exploiting exosomes-based nanoscaffolds for IPF treatment 利用基于外泌体的纳米支架特异性递送 siRNA 以治疗 IPF
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100929

Idiopathic pulmonary fibrosis (IPF) is a progressive pulmonary disease that leads to interstitial inflammation, lung damage, and eventually life-threatening complications. Among various pathologic factors, Smad4 is a pivotal molecule involved in the progression and exacerbation of IPF. It mediates nuclear transfer of Smad2/Smad3 complexes and initiates the transcription of fibrosis-promoting genes. Thus, the inhibition of Smad4 expression in pulmonary fibroblasts by small interfering RNAs (siRNAs) might be a promising therapeutic strategy for IPF. Herein, we engineered exosome membranes (EM) by cationic lipid (i.e., DOTAP) to load siRNAs against Smad4 (DOTAP/siSmad4@EM), and investigated their specific delivery to pulmonary fibroblasts for treating IPF in a mouse model via pulmonary administration. As reference nanoscaffolds, undecorated DOTAP/siSmad4 complexes (lipoplexes, consisting of cationic lipid DOTAP and siRNAs) and siSmad4-loaded lipid nanoparticles (DOTAP/siSmad4@lipo, consisting of lipoplexes fused with DPPCChol liposomes) were also prepared. The results showed that DOTAP/siSmad4@EM exhibited a higher cellular uptake and gene silencing efficacies in mouse pulmonary fibroblasts (viz., MLg2908) as compared to the two reference nanoscaffolds. Furthermore, the outcomes of the in vivo experiments illustrated that DOTAP/siSmad4@EM could significantly down-regulate the Smad4 expression with augmented anti-fibrosis efficiency. Additionally, the DOTAP/siSmad4@EM conferred excellent biocompatibility with low cytokine levels in bronchoalveolar lavage fluid and proinflammatory responses in the pulmonary area. Taken together, the outcomes of our investigation imply that specific inhibition of Smad4 expression in pulmonary fibroblasts by pulmonary administrated DOTAP/siSmad4@EM is a promising therapeutic strategy for IPF, which could safely and effectively deliver siRNA drugs to the targeted site of action.

特发性肺纤维化(IPF)是一种进行性肺部疾病,会导致肺间质炎症、肺损伤,最终引发危及生命的并发症。在各种病理因素中,Smad4 是参与 IPF 进展和恶化的关键分子。它介导 Smad2/Smad3 复合物的核转移,并启动纤维化促进基因的转录。因此,通过小干扰 RNAs(siRNAs)抑制肺成纤维细胞中 Smad4 的表达可能是治疗 IPF 的一种有前景的策略。在此,我们用阳离子脂质(即 DOTAP)设计了外泌体膜 (EM),以装载针对 Smad4 的 siRNAs(DOTAP/siSmad4@EM),并研究了通过肺部给药将其特异性地输送到肺成纤维细胞以治疗小鼠模型中的 IPF。作为参考纳米支架,还制备了未装饰的 DOTAP/siSmad4 复合物(lipoplexes,由阳离子脂质 DOTAP 和 siRNA 组成)和 siSmad4 负载脂质纳米颗粒(DOTAP/siSmad4@lipo,由与 DPPCChol 脂质体融合的 lipoplexes 组成)。结果表明,与两种参考纳米支架相比,DOTAP/siSmad4@EM在小鼠肺成纤维细胞(即MLg2908)中表现出更高的细胞吸收率和基因沉默效率。此外,体内实验结果表明,DOTAP/siSmad4@EM 能显著下调 Smad4 的表达,提高抗纤维化效率。此外,DOTAP/siSmad4@EM 还具有良好的生物相容性,支气管肺泡灌洗液中的细胞因子水平和肺部的促炎反应较低。综上所述,我们的研究结果表明,通过肺部给药 DOTAP/siSmad4@EM 特异性抑制肺成纤维细胞中 Smad4 的表达是治疗 IPF 的一种很有前景的策略,它可以安全有效地将 siRNA 药物输送到靶向作用位点。
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引用次数: 0
Targeted degradation of LRG1 to attenuate renal fibrosis 靶向降解 LRG1 以减轻肾脏纤维化
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100941

Leucine-rich α-2 glycoprotein 1 (LRG1), a secreted glycoprotein, has been identified as significantly upregulated in renal fibrosis, potentially exacerbating the condition by enhancing TGF-β-Smad3-dependent signaling pathways. Herein, utilizing our developed LRG1-targeting peptide for LRG1 recruitment and lenalidomide for E3 ubiquitin ligase engagement, we developed an advanced proteolysis targeting chimera, ETTAC-2, specifically designed for LRG1 degradation. Our cellular degradation assays validated that ETTAC-2 effectively degraded LRG1 through a proteasome-dependent mechanism, achieving half-maximal degradation at a concentration of 8.38 µM. Furthermore, anti-fibrotic experiments conducted both in vitro and in vivo revealed that ETTAC-2 efficiently induced LRG1 degradation in fibrotic kidneys. This action effectively inhibited the TGF-β-Smad3 signaling pathway and diminished the secretion of fibrosis-associated proteins, consequently attenuating the progression of renal fibrosis. Our study highlights the pivotal role of LRG1 in renal fibrosis and positions ETTAC-2 as a promising therapeutic candidate for targeted LRG1 intervention.

富亮氨酸α-2糖蛋白1(Leucine-rich α-2 glycoprotein 1,LRG1)是一种分泌性糖蛋白,在肾脏纤维化中被发现明显上调,可能通过增强TGF-β-Smad3依赖性信号通路而加重病情。在此,我们利用开发的 LRG1 靶向肽来招募 LRG1,利用来那度胺来参与 E3 泛素连接酶,开发了一种高级蛋白水解靶向嵌合体 ETTAC-2,专门用于降解 LRG1。我们的细胞降解实验验证了 ETTAC-2 通过蛋白酶体依赖机制有效降解了 LRG1,在 8.38 µM 的浓度下达到半最大降解。此外,体外和体内抗纤维化实验表明,ETTAC-2 能有效诱导纤维化肾脏中 LRG1 的降解。这一作用有效地抑制了 TGF-β-Smad3 信号通路,减少了纤维化相关蛋白的分泌,从而减轻了肾脏纤维化的进展。我们的研究强调了 LRG1 在肾脏纤维化中的关键作用,并将 ETTAC-2 定位为 LRG1 靶向干预的候选疗法。
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引用次数: 0
Rational fusion design inspired by cell-penetrating peptide: SS31/S-14 G Humanin hybrid peptide with amplified multimodal efficacy and bio-permeability for the treatment of Alzheimer's disease 受细胞穿透肽启发而进行的合理融合设计:SS31/S-14 G 人源素混合肽具有更强的多模式疗效和生物渗透性,可用于治疗阿尔茨海默病
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100938

Alzheimer's disease is a neurodegenerative disease induced by multiple interconnected mechanisms. Peptide drug candidates with multi-modal efficacy generated from fusion strategy are suitable for addressing multi-facet pathology. However, clinical translation of peptide drugs is greatly hampered by their low permeability into brain. Herein, a hybrid peptide HNSS is generated by merging two therapeutic peptides (SS31 and S-14 G Humanin (HNG)), using a different approach from the classical shuttle-therapeutic peptide conjugate design. HNSS demonstrated increased bio-permeability, with a 2-fold improvement in brain distribution over HNG, thanks to its structure mimicking the design of signal peptide-derived cell-penetrating peptides. HNSS efficiently alleviated mitochondrial dysfunction through the combined effects of mitochondrial targeting, ROS scavenging and p-STAT3 activation. Meanwhile, HNSS with increased Aβ affinity greatly inhibited Aβ oligomerization/fibrillation, and interrupted Aβ interaction with neuron/microglia by reducing neuronal mitochondrial Aβ deposition and promoting microglial phagocytosis of Aβ. In 3× Tg-AD transgenic mice, HNSS treatment efficiently inhibited brain neuron loss and improved the cognitive performance. This work validates the rational fusion design-based strategy for bio-permeability improvement and efficacy amplification, providing a paradigm for developing therapeutic peptide candidates against neurodegenerative disease.

阿尔茨海默病是一种由多种相互关联的机制诱发的神经退行性疾病。融合策略产生的多肽候选药物具有多模式疗效,适用于解决多方面的病理问题。然而,多肽药物在大脑中的低渗透性极大地阻碍了其临床转化。本文采用不同于经典的穿梭肽-治疗肽共轭物设计方法,将两种治疗肽(SS31 和 S-14 G Humanin (HNG))融合在一起,生成了混合肽 HNSS。由于其结构模仿了信号肽衍生的细胞穿透肽的设计,HNSS 的生物渗透性得到了提高,与 HNG 相比,HNSS 在大脑中的分布范围扩大了 2 倍。HNSS 通过线粒体靶向、清除 ROS 和激活 p-STAT3 的综合作用,有效缓解了线粒体功能障碍。同时,增加了 Aβ 亲和力的 HNSS 可大大抑制 Aβ 的寡聚/纤化,并通过减少神经元线粒体 Aβ 沉积和促进小胶质细胞吞噬 Aβ 来阻断 Aβ 与神经元/小胶质细胞的相互作用。在 3 × Tg-AD 转基因小鼠中,HNSS 治疗有效地抑制了脑神经元的损失并改善了认知能力。这项工作验证了基于合理融合设计的改善生物渗透性和提高疗效的策略,为开发治疗神经退行性疾病的候选多肽提供了范例。
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引用次数: 0
Co-delivery of retinoic acid and miRNA by functional Au nanoparticles for improved survival and CT imaging tracking of MSCs in pulmonary fibrosis therapy 通过功能性金纳米颗粒联合递送维甲酸和 miRNA,提高间充质干细胞在肺纤维化治疗中的存活率并进行 CT 成像跟踪
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100944

Mesenchymal stem cells (MSCs) have emerged as promising candidates for idiopathic pulmonary fibrosis (IPF) therapy. Increasing the MSC survival rate and deepening the understanding of the behavior of transplanted MSCs are of great significance for improving the efficacy of MSC-based IPF treatment. Therefore, dual-functional Au-based nanoparticles (Au@PEG@PEI@TAT NPs, AuPPT) were fabricated by sequential modification of cationic polymer polyetherimide (PEI), polyethylene glycol (PEG), and transactivator of transcription (TAT) penetration peptide on AuNPs, to co-deliver retinoic acid (RA) and microRNA (miRNA) for simultaneously enhancing MSC survive and real-time imaging tracking of MSCs during IPF treatment. AuPPT NPs, with good drug loading and cellular uptake abilities, could efficiently deliver miRNA and RA to protect MSCs from reactive oxygen species and reduce their expression of apoptosis executive protein Caspase 3, thus prolonging the survival time of MSC after transplantation. In the meantime, the intracellular accumulation of AuPPT NPs enhanced the computed tomography imaging contrast of transplanted MSCs, allowing them to be visually tracked in vivo. This study establishes an Au-based dual-functional platform for drug delivery and cell imaging tracking, which provides a new strategy for MSC-related IPF therapy.

间充质干细胞(MSCs)已成为治疗特发性肺纤维化(IPF)的有希望的候选细胞。提高间充质干细胞的存活率和加深对移植间充质干细胞行为的了解对于提高基于间充质干细胞的特发性肺纤维化治疗效果具有重要意义。因此,通过在AuNPs上依次修饰阳离子聚合物聚醚酰亚胺(PEI)、聚乙二醇(PEG)和转录激活因子(TAT)渗透肽,制备了双功能金基纳米颗粒(Au@PEG@PEI@TAT NPs,AuPPT),以共同递送维甲酸(RA)和microRNA(miRNA),从而同时提高间充质干细胞的存活率,并在IPF治疗过程中对间充质干细胞进行实时成像追踪。AuPPT NPs具有良好的载药能力和细胞摄取能力,能有效地递送miRNA和RA,保护间充质干细胞免受活性氧的损伤,并降低间充质干细胞凋亡执行蛋白Caspase 3的表达,从而延长间充质干细胞移植后的存活时间。同时,AuPPT NPs在细胞内的蓄积增强了移植间充质干细胞的计算机断层扫描成像对比度,从而可以在体内对其进行可视化追踪。这项研究建立了一个基于金的药物递送和细胞成像追踪双功能平台,为间叶干细胞相关的 IPF 治疗提供了一种新策略。
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引用次数: 0
Vat-based photopolymerization 3D printing: From materials to topical and transdermal applications 釜基光聚合三维打印:从材料到局部和透皮应用
IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pub Date : 2024-08-01 DOI: 10.1016/j.ajps.2024.100940

Three-dimensional (3D) printing is an innovative manufacturing method with the potential to revolutionize topical and transdermal dosage forms. Nowadays, it is established that Vat-based photopolymerization (VP) 3D printing technologies offer superior printing efficiency and versatility compared to other 3D printing technologies available on the market. However, there are some limitations that impair their full application in pharmaceutical contexts, such as the lack of a range of biocompatible materials for topical and transdermal applications. This review article explores all types of VP-based 3D printing and discusses the relevance of implementing this kind of technology. We start with a detailed description of the printing process, focusing on the commercial materials available and lab-made resins proposed by different authors. We also review recent studies in this field, which mainly focus on the fabrication of transdermal devices based on microneedle arrays. In the future, it is expected that the manufacturers of 3D printers invest in modifications to the printing apparatus to allow the simultaneous printing of different resins and/or compound types, which will open frontiers to the personalization of treatment approaches.

三维(3D)打印是一种创新的制造方法,有望彻底改变外用和透皮剂型。如今,与市场上的其他三维打印技术相比,基于蒸馏罐的光聚合(VP)三维打印技术具有更高的打印效率和多功能性。然而,这些技术在制药领域的全面应用还存在一些局限性,例如缺乏一系列用于局部和透皮应用的生物相容性材料。这篇综述文章探讨了各种基于 VP 的 3D 打印技术,并讨论了采用这种技术的意义。我们首先详细介绍了打印过程,重点是现有的商业材料和不同作者提出的实验室自制树脂。我们还回顾了该领域的最新研究,主要集中在基于微针阵列的透皮装置的制造上。未来,3D 打印机制造商有望投资改造打印设备,以便同时打印不同的树脂和/或化合物类型,这将为个性化治疗方法开辟新的领域。
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引用次数: 0
期刊
Asian Journal of Pharmaceutical Sciences
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