Biomaterials Science
·
2024
·
IF 5.8
Yongzhi Chen,Qiuxia Tan,Yuanyu Tang,E. Pang,Rui Peng,Minhuan Lan,Dousheng Bai
Hepatocellular carcinoma (HCC) is characterized by a high degree of malignancy and mortality. Sorafenib (SOR), a multi-kinase inhibitor, is clinically used in the treatment of HCC. However, SOR suffers from serious side effects and drug resistance. The development of novel therapeutic strategies for HCC therapy is urgently needed. Sonodynamic therapy (SDT) has unique advantages in treating deep tumors due to the merits of deep tissue penetration, low side effects, and the absence of drug resistance. Here, we developed multifunctional nanoparticles (NPs) termed SOR-TCPP@PEG-FA by assembling SOR, tetrakis (4-carboxyphenyl) porphyrin (TCPP), and folic acid (FA)-modified DSPE-PEG. The FA group enhances the tumor targeting capability of these NPs, while TCPP generates ROS under ultrasound (US) irradiation, which are toxic to tumor cells, and SOR with chemotherapeutic effects is released, thus realizing the synergistic SDT and chemotherapy of tumors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Yiming Wang,Chen Wang,Yuan Lu
Nucleic acids have attracted increasing attention as drugs due to their fascinating advantages, such as long-term efficacy and ease of preparation compared to proteins. The nucleic acid therapy relies heavily on delivery vectors, which can prevent the degradation of nucleic acids while assisting them in cellular internalization. However, commonly used nonviral vector liposomes easily accumulate in the liver, which can limit their application in extrahepatic diseases. Herein, a potential spleen targeting vector for nucleic acids is developed based on the metal–organic frameworks. The plasmids are encapsulated inside the nanoscale zeolitic imidazolate framework (ZIF) via coprecipitation. The co-encapsulation of the cationic polymer poly(ether imide) (PEI) and the stabilizer polyvinylpyrrolidone (PVP) can significantly improve particle dispersion and stability. The prepared nanoparticles allow efficient transfection in vitro, mainly through clathrin-mediated and caveolae-mediated endocytosis. The biodistribution in mice shows that 46% of the nanoparticles accumulate in the spleen, which is much higher than that of the liposomes. The vector can successfully deliver plasmids to extrahepatic organs for protein synthesis and even induce an immune response. The elaborate ZIF-based nanoparticle may offer a new route for extrahepatic, especially spleen targeting delivery for the nucleic acids.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2024
·Vol. 191
·期 5
·1-11
·
IF 5.3
Zhan Ying,Mao Yichun,Sun Pei,Liu Chenbin,Gou Hongquan,Qi Haipeng,Chen Guifang,Hu Song,Tian Bo
Abstract Tumor-associated antigen (TAA)–based diagnosis has gained prominence for early tumor screening, treatment monitoring, prognostic assessment, and minimal residual disease detection. However, limitations such as low sensitivity and difficulty in extracting non-specific binding membrane proteins still exist in traditional detection methods. Upconversion luminescence (UCL) exhibits unique physical and chemical properties under wavelength near-infrared light excitation. Rolling circle amplification (RCA) is an efficient DNA amplification technique with amplification factors as high as 10 5 . Therefore, the above two excellent techniques can be employed for highly accurate imaging analysis of tumor cells. Herein, we developed a novel nanoplatform for TAA-specific cell imaging based on UCL and RCA technology. An aptamer–primer complex selectively binds to Mucin 1 (MUC1), one of TAA on cell surface, to trigger RCA reaction, generating a large number of repetitive sequences. These sequences provide lots of binding sites for complementary signal probes, producing UCL from lanthanide-doped upconversion nanoparticles (UCNPs) after releasing quencher group. The experimental results demonstrate the specific attachment of upconversion nanomaterials to cancer cells which express a high level of MUC1, indicating the potential of UCNPs and RCA in tumor imaging. Graphical Abstract
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Weixia Qin,Junjie Cui,Usama,Yan Li,Rui Liu,Zhaohua Miao,Zhengbao Zha,Lei Jiang,Ming Cao,Mina Ibrahim Tadros,Antonio Claudio Tedesco,Zijian Li,Hong Bi
The combination of photodynamic therapy (PDT) with sonodynamic therapy (SDT) can compensate for shortcomings of PDT, such as the limited tissue penetration depth or low efficiency of reactive oxygen species (ROS) generation of SDT, but it is still a great challenge to design and synthesize an ideal photo-/sono-sensitizer with a satisfactory targeting capability and biosafety. Herein, a novel type of carbon dots (CDs) containing morpholino surface group and the photo-/sono-sensitive core is synthesized by using levofloxacin and methylene blue as precursors via a hydrothermal synthesis. The as-synthesized CDs show a highly efficient generation of singlet oxygen ( 1 O 2 ) under a red laser irradiation while producing 1 O 2 and hydroxyl radical (·OH) under a low-intensity pulsed US stimulation, which leads to a remarkably enhanced ROS production yield in combined PDT and SDT of breast tumor. In the meantime, the CDs demonstrate a lysosome-targeting ability in breast tumor cells, which causes lysosomal damage and release of acid phosphatase, resulting in massive apoptosis of cells and more than 90% of cell death. Further, in vivo experimental results confirm the effect of the CDs to inhibit or even eliminate the tumor growth of 4T1 tumor-bearing mice after the combined PDT and SDT.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Zhen Zhang,Hongbo Wang,Zhijun Zhang,Yaoyao Zhang,Huajing Sun,Xi Chen,Jiayu Gu,Yanling Gong
Small interfering RNA (siRNA)-based therapy, which silences disease-associated genes, has emerged as a potential therapeutic strategy for various disorders, including cancer. Lipid nanoparticles (LNPs) have become a leading platform for efficient siRNA delivery. SOX9, a family member of SRY-related high-mobility-group box (SOX) transcription factors, plays an important role in the pathogenesis and progression of colorectal cancer (CRC). Here, we developed cRGDfK peptide-modificed LNPs (R-LNPs) composed of DLin-MC3-DMA, DMG-PEG, DSPC, DSPE-PEG-cRGDfK, and cholesterol for the targeted delivery of SOX9 siRNA (siSOX9) in CRC treatment. The formulation, delivery, and antitumor effect on CRC in vitro and in vivo were explored. The optimized R-LNPs exhibited favorable physicochemical properties including a uniform particle size (159.6 ± 0.93 nm), low polydispersity index (PDI = 0.207 ± 0.016), near-neutral zeta potential (2.74 ± 0.35 mV), and high encapsulated efficiency (90.71 ± 1.63%). Additionally, R-LNPs demonstrated sustained and controlled in vitro release and good serum stability. The prepared R-LNPs were efficiently uptaken by HCT-116 via clathrin, lipid rafts, and caveolae dependent endocytosis and macropinocytosis. Subsequently, R-LNPs were colocalized with lysosomes before escaping into the cytoplasm, ensuring effective siRNA release. In vivo distribution studies confirmed tumor-specific accumulation for R-LNPs in HCT-116 xenograft models. Functionally, R-LNPs loading siSOX9 inhibited the proliferation, migration, and invasion of HCT-116 cells and Caco-2 cells (P < 0.05 or 0.01) and inhibited tumor growth and proliferation in tumor-bearing mice (P < 0.05 or 0.01). The antitumor effects were attributed to the silence of SOX9, which subsequently downregulated key oncogenic mediators, including β-catenin, cyclin D1, and c-Myc (P < 0.05 or 0.01). Furthermore, R-LNPs demonstrated favorable safety in in vivo application. In conclusion, our cRGDfK-modified LNPs loading siSOX9 represent a promising targeted therapeutic strategy for CRC, offering both efficacy and biocompatibility.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2025
·
IF 5.4
Hongdong Song,Yaqiong Chen,Ruihan Huang,Xiao Guan
To enhance the oral bioavailability and hypoglycemic effect of insulin, we developed a novel bilayer liposome delivery system in this study. The outer layer of this system was decorated with propanoic acid-functionalized chitosan (CS/PA) to improve gastrointestinal stability and facilitate intestinal targeting of mono-carboxylate transporter protein 1 (MCT1). We encapsulated insulin in this newly developed delivery system. The CS/PA coating significantly enhanced the protective effect of liposomes on insulin in the gastrointestinal environment. Experiments using Caco-2 cells and ligated intestinal loops showed that IN-LIP-CS/PA facilitated insulin absorption and increased intestinal permeability. Importantly, MCT1-mediated energy-dependent endocytosis played a crucial role in the absorption process. Additionally, endocytosis of IN-LIP-CS/PA was mediated through clathrin, lipid raft, caveolin, and macropinocytosis. Furthermore, the endoplasmic reticulum and Golgi apparatus were mainly involved in the intracellular transport of IN-LIP-CS/PA. The combination of MCT1-mediated endocytosis and the intracellular transport pathways may help IN-LIP-CS/PA avoid lysosomal degradation, thereby improving the intracellular transport efficiency of insulin. In vivo studies demonstrated that IN-LIP-CS/PA achieved a significantly better hypoglycemic effect. These findings suggested that the newly developed bilayer liposome delivery system holds promise as an effective platform for the oral delivery of insulin.
✓ 已验证
产品关联
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Yujing Lu,Yicheng Guo,Lina Wang,Yoshimasa Nakamura,Hang Qi
Polyphenols extracted from Ascophyllum nodosum (PEAn) exhibit significant bioactivities but are limited by poor photothermal stability and low membrane permeability, which hinder their applications. This study explores the use of royal jelly exosomes (RExo) as a novel food-derived nanocarrier to enhance the stability and targeted delivery of PEAn. RExo (105.01 ± 7.24 nm) demonstrated a spherical morphology and expressed key exosomal markers (CD63, CD81, TSG101), enriched in metabolism-related proteins. The yield of RExo was optimized to a 12.72-fold increase at pH 6.0 compared to pH 2.0. Ultrasound-assisted loading achieved 85.73 ± 1.73 % encapsulation efficiency, as confirmed by spectroscopic analysis. Encapsulation significantly enhanced the photothermal stability and gastrointestinal tolerance of PEAn. In B16F10 cells, RExo improved PEAn uptake, inhibited tyrosinase activity, reduced melanin synthesis, and suppressed cell migration. Mechanistically, the anti-melanogenic effect of PEAn-RExo may be partially dependent on autophagy induction. This study provides a promising natural strategy for the development of functional foods and personalized nutrient delivery systems.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xiaochun Wu,Yan Xu,Dandan Zhu,Weiye Zhang,Yanjun Yang,Liang Feng,Bing Yang,Xiaobin Jia
Understanding the absorption of natural polysaccharides is crucial for advancing their development and application. However, their oral absorption mechanisms and potential applications remain unclear. In this study, Astragalus homogeneous polysaccharide (APS3a) was isolated and characterized. Based on the structural analysis, in vitro and in vivo tracking of APS3a was conducted using FITC- and Cy7 amine labeling to investigate its transport and absorption mechanisms. The results indicated that APS3a can traverse the intestinal mucus layer and is mainly absorbed in the jejunum, subsequently distributing gradually to the liver and kidneys. Further investigation of its transport mechanism revealed that APS3a undergoes energy-dependent active transport, utilizing transcellular transport pathways such as caveolin-mediated endocytosis, macropinocytosis, and sodium-glucose cotransporter 1 (SGLT1)-mediated endocytosis. Additionally, APS3a has the capacity to reversibly open tight junction proteins, facilitating transport through the paracellular transport pathway. Moreover, APS3a can function as an excipient, self-assembling with flavonoids from Astragalus Radix to form complexes, thereby enhancing the permeability and absorption of these flavonoids. These findings provide valuable insights into the oral absorption of APS3a and its potential applications, which are significant for the development and application of polysaccharides.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Jie Meng,Shuang Xie,Zhanlin Zhang,Pan Ran,Xia Lei,Long He,Xiaohong Li
Pyroelectrodynamic therapy (PEDT) of tumors faces challenges due to its low electrocatalytic efficiency at mild temperature and the potential for off-target toxicity to healthy tissue. To overcome these issues, we have engineered pyroelectric nanoparticles (NPs) that feature a pH-triggered heterojunction structure and tumor-selective reactive oxidative species (ROS) production, faclitating synergistic PEDT and mild photothermal therapy (PTT). Herein, molybdenum trioxide (MoO 3 ) was deposited in-situ on the surface of tetragonal BaTiO 3 (tBT) to create tBT@MO. Subsequently, a metal-acid treatment was utrilized to hydrogenate MoO 3 , and the yielded HMO was grafted with poly(ethylene glycol) (PEG) to produce tBT@HMO-PEG. In contrast to vulnerability in normal tissues, hydrogen-doped NPs exhibit stability against H + attacks in the slightly acidic microenvironment of tumors, faclitating efficient near-infrared II (NIR-II) absorption, and the enhanced photothermal conversion enables tumor-selective mild PTT and PEDT. The formation of heterojunctions between tBT and HMO markedly improves electron-hole separations and ROS productions, and the generated pyroelectric field selectively disrupts the membrane potentials of tumor cells, theraby promoting NP internalization. In a tumor-bearing model, NPs exhibit deep tumor penetration and widesperead ROS distribution, overcoming the limitations of the short lifespan and diffusion distance of ROS to achieve potent antitumor efficacy. Moreover, the tumor-selective PEDT and mild hyperthermia ensure treatment safety. Therefore, the innovative design of pH-triggered Schottky heterojunctions effectively mitigate off-target toxicity to normal tissue while improving the precision and efficacy of tumor therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2024
·
IF 4.6
Zhaoxin Xia,Yulong Liao,Ge Gao,Shiyong Zhang
The poor accumulation of antibiotics in the cytoplasm leads to the poor eradication of intracellular bacteria. Herein, a polyelectrolyte complex (PECs@Rif) allowing direct cytosolic delivery of rifampicin (Rif) was developed for the treatment of intracellular infections by complexation of poly(α-lipoic acid) (pLA) and oligosaccharide (COS) in water and loading Rif. Due to the thiol-mediated cellular uptake, PECs@Rif delivered 3.9 times higher Rif into the cytoplasm than that of the free Rif during 8 h of incubation. After entering cells, PECs@Rif released Rif by dissociating pLA into dihydrolipoic acid (DHLA) in the presence of intracellular thioredoxin reductase (TrxR). Notably, DHLA could reduce endogenous Fe(III) to Fe(II) and provide a catalyst for the Fenton reaction to produce a large amount of reactive oxygen species (ROS), which would assist Rif in eradicating intracellular bacteria. In vitro assay showed that PECs@Rif reduced almost 2.8 orders of magnitude of intracellular bacteria, much higher than 0.7 orders of magnitude of free Rif. The bacteremia-bearing mouse models showed that PECs@Rif reduced bacterial levels in the liver, spleen, and kidney by 2.2, 3.7, and 2.3 orders of magnitude, respectively, much higher than free Rif in corresponding tissues. The direct cytosolic delivery in a thiol-mediated manner and enhanced oxidative stress proposed a feasible strategy for treating intracellular bacteria infection.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Dan Yang,Yuqi Feng,Ying Yuan,Linxuan Zhang,Yao Zhou,Adam C. Midgley,Yanrong Wang,Ning Liu,Guoliang Li,Xiaolin Yao,Dechun Liu
The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an “active PC” to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of “passive PCs” formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Zhong Shao,Ke Li,Hao Guo,Yangyang Cheng,Shiyong Zhang
Hypertensive chronic kidney disease (CKD) remains incurable, mainly because the current therapies are difficult to concurrently target elevated blood pressure and multifaceted renal abnormalities. Herein, we present an oral H 2 S nanomedicine, poly(lipoic acid trisulfide) (pLATS), with synergistic antihypertensive and renoprotective activities for treating hypertensive CKD. pLATS not only enables efficient oral delivery across multiple biological barriers via trisulfide exchange with thiols at mucosal, epithelial, and renal cellular interfaces, but also undergoes thiol-triggered intracellular depolymerization to achieve sustained release H 2 S and lipoic acid (LA)/LATS over 60 h, with H 2 S exerting multifactorial regulatory effects underlying hypertensive CKD. Meanwhile, LA/LATS upregulate H 2 S-producing enzymes, promoting sustained endogenous H 2 S biogenesis. In vivo, pLATS demonstrates markedly improved pharmacokinetics over its monomeric precursor, effectively lowering blood pressure, urine albumin-to-creatinine ratio, and plasma urea and creatinine by modulating genes in the renin-angiotensin system and endothelial function, surpassing the clinical antihypertensive losartan. In essence, this study pioneers a paradigm for comprehensive treatment of hypertensive CKD, with potential applications extending to broader chronic diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）