Drug Delivery and Translational Research
·
2026
·
IF 6.9
Yuan Hao,Zhang Bingwen,Sun Wen,Liu Haofan,Hu Liandong
In this study, celecoxib (CXB) microspheres (CM) and ropivacaine (RPV) microspheres (RM) were prepared respectively. A poly (D, L-lactide-co-glycolide)-block-poly (ethylene glycol)-block-poly (D, L-lactide-co-glycolide) (PLGA–PEG–PLGA, PPP) was synthesized by copolymerizing glycolide and lactide with polyethylene glycol. CM, RM, and hydroxyapatite (HA) were then incorporated into PPP solution to construct the microsphere–hydrogel system (CRMH hydrogels). CM, RM, and CRMH were systematically characterized in terms of morphology, physicochemical properties, pH-buffering capacity, and degradation behavior. The pH-dependent drug release and release kinetics of the individual CM, RM and the CRMH hydrogels were also investigated. In vitro release studies demonstrated that CRMH hydrogels provided coordinated, sustained release of CXB and RPV at pH 6.2. In a rabbit osteoarthritis (OA) model, intra-articular (IA) administration of CRMH hydrogels achieved sustained drug retention and release within the joint cavity, and effectively promoted articular cartilage repair. Overall, the CRMH hydrogels showed promising synergistic therapeutic potential for OA.
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Communications
·
2025
·
IF 4.5
Gengsheng Shi,Wenqin Yin,Jing Luo,Song Lin,Linluo Zhang,Yuan He,Hui Ding
This study developed transferrin (Tf) -functionalized magnetic nanoparticles (Tf-MNP-PEG-PLGA-Cur) to enhance curcumin (Cur)’s therapeutic potential for lung cancer. Tf-MNP-PEG-PLGA-Cur was synthesized by chemically coupling Tf (tumor-targeting ligand) to the surface of MNP-PEG-PLGA-Cur. Its size and morphology were measured, in vitro drug release was evaluated via dialysis, oral bioavailability and tissue distribution were studied in rats and mice. Cytotoxicity to normal cells was tested by CCK-8, A549 cell uptake was observed by confocal laser microscopy, and in vitro anti-lung cancer activity was studied using MTT assay. In vivo, its distribution in tumor-bearing nude mice was detected by near-infrared imaging, followed by measuring tumor growth and histopathological observation. Tf-MNP-PEG-PLGA-Cur nanoparticles had a small size (137.39 ± 3.72 nm, PDI 0.224 ± 0.010) with a biphasic release pattern, longer half-life (P<0.05), and 186% relative oral bioavailability. It promoted Cur accumulation in tissues, especially liver and spleen. Both Tf-MNP-PEG-PLGA-Cur and Cur showed good cytocompatibility. Tf-MNP-PEG-PLGA-Cur enhanced curcumin's anti-lung cancer activity in vitro and in vivo, indicating good tumor-targeting. H&E staining showed it protected nude mice's vital organs and inhibited tumor growth. Tf-MNP-PEG-PLGA-Cur is a promising polymeric sustained-release curcumin preparation, improving oral bioavailability and anti-lung cancer activity.
✓ 已验证
产品关联
DOI
高影响因子
Pharmaceutics
·
2025
·Vol. 17
·期 3
·376
·
IF 5.5
Yuxing Zhang,Xixi Zou,Qiran Du,Xiaotao Dong,Uday Kumar Chinta,Ruyue Yu,Fei Wu,Tuo Jin
Objectives: Thermo-gelling hydrophilic polymers like PLGA–PEG–PLGA are known as injectable sustained-release depots for biologics, but they face challenges due to the occurrence of severe burst release. This study aimed to develop a strategy to avoid the initial burst release by pre-encapsulating proteins in polysaccharide microparticles through an aqueous–aqueous emulsion mechanism, thereby enhancing therapeutic retention and linear release kinetics.Methods: Five model proteins (G-CSF, GM-CSF, IGF-1, FVIII, BSA) were encapsulated in dextran microparticles, using an organic solvent-free aqueous–aqueous emulsion method. These particles were dispersed in a 23% (w/w) PLGA–PEG–PLGA solution and injected into a 37 °C release buffer to form a gel depot. The in vitro release profiles were quantified using ELISA and MicroBCA assays over 9–42 days. The bioactivity of the proteins was validated using cell proliferation assays (NFS-60, TF-1, MCF-7) and chromogenic kits. The in vivo pharmacokinetics of the FVIII-loaded formulations were evaluated in Sprague–Dawley rats (n = 5/group) over 28 days.Results: Protein-loaded dextran particles retained their structural integrity within the hydrogel and exhibited minimal burst release (≤5% within 30 min vs. >25% for free proteins). Sustained near-linear release profiles were observed for all the proteins, with complete release by day 9 (G-CSF, GM-CSF, BSA) or day 42 (FVIII). Rats administered with the thermal gel with FVIII–dextran particles showed a significantly lower peak plasma concentration (Cmax: 88.25 ± 30.21 vs. 132.63 ± 66.67 ng/mL) and prolonged therapeutic coverage (>18 days vs. 15 days) compared to those administered with the thermal gel with the FVIII solution. The bioactivity of the released proteins remained at ≥90% of the native forms.Conclusions: Pre-encapsulation in dextran microparticles effectively mitigates burst release from thermosensitive hydrogels, while preserving protein functionality.
研究领域:
药剂学
·
生物医学工程
·
药物递送系统
·
蛋白质工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Zhen Wang,Bixi Ding,Yuanpei Zhao,Yue Han,Yu Sheng,Ling Tao,Xiangchun Shen,Jianping Zhou,Lei Jiang,Yang Ding
Increasing knowledge of drug delivery properties, tumor profiles and their relationship promotes precise administration regimens, representing a promising pattern to personalized tumor treatment. Herein, we propose a regulatory hydrogel depot toward metastatic cancer by establishing mathematical models between tumor characteristics and administration regimens. Specifically, a thermo-sensitive PLGA-PEG-PLGA polymer is introduced as injectable hydrogel matrix, of which the administration volume and frequency are manipulated elaborately according to tumor size and gel-degradation kinetics. Structurally, doxorubicin (Dox) and arginine-terminated nanoparticles containing KIAA1199 specific shRNA ( shKIAA RPDNs) are incorporated into hydrogels, thereby formulating a topical and sustained drug depot to achieve synergy treatment. For dual-targeting therapy, Dox interdicts DNA replication/transcription, and shKIAA persistently silences KIAA1199 protein to modulate aggressive phenotypes. After individual peritumoral injection, Gel/ shKIAA RPDNs/Dox demonstrates desirable distribution patterns and gel degradation kinetics with enhanced tumor penetration. Moreover, a preferable inhibition of tumor proliferation and metastasis is confirmed after twice treatment in 12 days, indicating better therapeutic efficacy with less dosage and frequency. Consequently, the controllable administration regimen inspired mathematical models of thermosensitive hydrogel provides an intelligent platform for personalized treatment to metastatic cancer.
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2026
·Vol. 16
·期 23
·20895-20907
·
IF 6.1
Xiaolong Xu,Yuze Zhou,Junhao Chen,Lujing Fei,Min Qi
The treatment of malignant melanoma, an aggressive skin cancer with high recurrence and metastatic potential, often presents challenges due to systemic toxicity and multidrug resistance in current therapies. In this study, we develop a localized therapeutic platform by integrating methotrexate–manganese (MTX–Mn) coordination nanoparticles into a thermosensitive PLGA–PEG–PLGA (PPP) hydrogel to achieve sustained and site-specific drug delivery for melanoma treatment. MTX–Mn nanoparticles were synthesized through coordination-driven self-assembly and comprehensively characterized by FTIR, 1H NMR, TEM, EDS, and zeta potential analyses, confirming successful coordination and uniform nanoscale features. In vitro experiments demonstrated that MTX–Mn significantly inhibited melanoma cell proliferation and migration. Flow cytometry further revealed that MTX–Mn induced pronounced G0/G1 cell-cycle arrest and effectively promoted apoptosis, which was confirmed by TUNEL staining. Mechanistic investigations indicated that MTX–Mn triggered severe mitochondrial dysfunction, including ultrastructural damage, elevated mitochondrial ROS generation, and collapse of mitochondrial membrane potential (JC-1), suggesting a mitochondria-associated antitumor mechanism. In vivo, peritumoral administration of PPP/MTX–Mn markedly suppressed tumor growth in a melanoma-bearing mouse model, reduced the tumor burden, and significantly decreased Ki-67 expression. Histological evaluation of major organs by H&E staining revealed no obvious pathological abnormalities, supporting good in vivo biosafety. Overall, this MTX–Mn-loaded thermosensitive hydrogel provides a promising strategy for effective and safe localized melanoma therapy.
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2021
·
IF 15.881
Xiaozheng Zhao,Xiao Yang,Xudong Wang,Xiao Zhao,Yinlong Zhang,Shaoli Liu,Gregory J. Anderson,Seong-jin Kim,Yiye Li,Guangjun Nie
Pancreatic ductal adenocarcinoma (PDAC) cells are surrounded by a dense extracellular matrix (ECM), which greatly restricts the access of therapeutic agents, resulting in poor clinical response to chemotherapy. Transforming growth factor-β1 (TGF-β1) signaling plays a crucial role in construction of the desmoplastic stroma and provides potential targets for PDAC therapy. To surmount the pathological obstacle, we developed a size switchable nanosystem based on PEG–PLGA nanospheres encapsulated within liposomes for the combined delivery of vactosertib (VAC), a TGF-β1 receptor kinase inhibitor, and the cytotoxic drug paclitaxel (TAX). By surface modification of the liposomes with a peptide, APTEDB, the nanosystem can be anchored to abundant tumor-associated fibronectin in PDAC stroma and decreases its size by releasing encapsulated TAX-loaded nanospheres, as well as VAC after collapse of the liposomes. The inhibition of ECM hyperplasia by VAC allows TAX more ready access to the cancer cells in addition to its small size, thereby shrinking pancreatic tumor xenografts more effectively than a combination of the free drugs. This size switchable nanosystem enables sequential delivery of drugs at a fixed dose combination with simplified administration and provides an encouraging cascade approach of drug penetration for enhanced chemotherapy in cancers with a dense desmoplastic stroma.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2022
·
IF 2.712
QingXia Guan,XiaoYing Zhou,FangFang Yang,Xue Zhang,YanHong Wang,WeiNan Li,XiuYan Li
It is well known that Glycyrrhetnic acid (GA) has significant liver-targeting and anti-inflammatory effects. Syringopicroside (SYR) and Hydroxytyrosol (HT), the active components of the Chinese herb Syringa oblata Lindl, have earned great reputation for their potential in preventing or treating viral hepatitis type B. Therefore, we loaded SYR and HT into GA-conjugated PEG-PLGA, so that they could target the liver in additional to exerting their own pharmacological effects in a synergistic. However, the in vivo targeting and the low bioavailability of SYR and HT pose a huge challenge. Therefore, we synthesized GA-conjugated multi-component nano-drug delivery system (SH-GPP). SH-GPP had a regular spherical shape with a uniform size distribution of 110.5 ± 3.18 nm. We further evaluated the effects of SH-GPP in vitro and in vivo. In the in vivo experiment, we evaluated the following parameters: the serum ALT and AST values; liver tissue homogenate MDA and SOD; HE staining of the pathological liver sections; and the liver coefficient. In the in vitro studies, the following parameters were evaluated: cellular uptake of SH-GPP; wound healing/scratch assay; cellular apoptosis; cell cycle; HBsAg; and HBeAg content. SH-GPP had better anti-hepatitis B effect than Syringopicroside and hydroxytyrosol (SH) and NPP alone. The targeting ability of GA enabled HT and SYR in GPP to reach the liver accurately, and played a synergistic role to maximize their therapeutic effects. This study provides a novel strategy against hepatitis B virus, and also provides a feasible scheme for improving the low bioavailability of the active components of traditional Chinese medicine.
研究领域:
药理学
·
病毒学
·
纳米技术
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2018
·Vol. 11
·期 5
·2872-2884
·
IF 7.994
Iqbal Shoaib,Du Xiaojiao,Wang Jilong,Li Hongjun,Yuan Youyong,Wang Jun
Nanoparticle (NP) drug delivery systems have been successfully designed and implemented to orally deliver siRNAs for inflammatory disorders. However, the influence of surface charge on orally administered siRNA nanocarriers has not been investigated. In this study, we prepared structurally related poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG 5K - b -PLGA 10K ) NPs with the assistance of a synthesized lipid featuring surface amine groups for subsequent charge tuning. NPs were prepared by a double emulsion method, and their surface charge could be tuned and controlled by a succinylation reaction to yield NPs with different surface charges, while maintaining their size and composition. The prepared NPs were termed as aminated NPs (ANPs), plain NPs (PNPs), or carboxylated NPs (CNPs) based on their surface charge. All NPs exhibited the desired structural stability and siRNA integrity after enzymatic degradation. In vivo studies showed that ANPs significantly accumulated in inflamed colons, and they were successful in decreasing TNF-α secretion and mRNA expression levels while maintaining colonic histology in a murine model of acute ulcerative colitis (UC). This study described a methodology to modify the surface charge of siRNA-encapsulating polymeric NPs and highlighted the influence of surface charge on oral delivery of siRNA for localized inflammatory disorders.
研究领域:
药学科学
·
纳米技术
·
炎症性疾病
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Ling Wang,Jie Li,Danya Zhang,Songwei Tan,Guiying Jiang,Xueqian Wang,Fei Li,Ying Zhou,Pingbo Chen,Rui Wei,Ling Xi
Metastasis and recurrence are the main causes of failure in the treatment of ovarian cancer (OC). Immunotherapy has brought new opportunities for cancer treatment, but the presence of the immunosuppressive tumor microenvironment limits its application in OC. Here, we prepared a kind of intelligent nanomicelles that could inhibit OC metastasis and recurrence by combining photothermal tumor ablation and immune remodeling. In this study, Indocyanine green (ICG), a photosensitizer and Monophosphoryl lipid A (MPLA), a Toll-like receptor 4 agonist, were encapsulated into the core of PEG-PLGA nanocarrier, and the surface was further modified with tumor-targeting peptide TMTP1. The formed TP1-IM nanomicelles with enhanced tumor accumulation could enable robust photothermal ablation of the primary tumor, and induce immunogenic cell death, release tumor-associated antigens, and DAMPs to form an endogenous in situ tumor vaccine by a single intravenous injection, which could effectively inhibit the growth of OC. Moreover, PTT with TP1-IM nanomicelles in combination with programmed cell death ligand 1 (PD-L1) checkpoint blockade could induce strong anti-tumor immune responses, relieve the immunosuppressive tumor microenvironment, and thus effectively inhibit the metastasis of OC. In addition, the combination strategy could produce long-term immune memory effects in treated mice to prevent the recurrence of tumors. Our work provides a new and individualized strategy for the treatment of OC and is expected for clinical transformation in the future for most components are clinically approved.
研究领域:
癌症研究
·
纳米医学
·
免疫治疗
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Zhengyue Kang,Min Yang,Xiaoling Feng,Hongjian Liao,Zhifei Zhang,Yonghong Du
Purpose Triple negative breast cancer (TNBC) is challenging for effective remission due to its very aggressive, extremely metastatic and resistant to conventional chemotherapy. Herein, a multifunctional theranostic nanoparticle was fabricated to enhance tumor targeted imaging and promote focused ultrasound (FUS) ablation and chemotherapy and sonodynamic therapy (SDT). A multi-modal synergistic therapy can improve the therapeutic efficacy and prognosis of TNBC.Methods AS1411 aptamer modified PEG@PLGA nanoparticles encapsulated with perfluorohexane (PFH) and anti-cancer drug doxorubicin (DOX) were constructed (AS1411-DOX/PFH-PEG@PLGA) to enhance tumor targeted imaging to guide ablation and synergistic effect of FUS/chemotherapy. FUS was utilized to trigger the co-release of doxorubicin and simultaneously PFH phase transition and activate DOX for SDT effect. The physicochemical, phase-changeable imaging capability, biosafety of nanoparticles and multi-mode synergistic effects on growth of TNBC were thoroughly evaluated in vivo and in vitro.Results The synthesized AS1411-DOX/PFH-PEG@PLGA (A-DPPs) nanoparticles are uniformly round with an average diameter of 306.03 ± 5.35 nm and the zeta potential of −4.05 ± 0.13 mV, displaying high biosafety and FUS-responsive drug release in vitro and in vivo. AS1411 modified NPs specifically bind to 4T1 cells and elevate the ultrasound contrast agent (UCA) image contrast intensity via PFH phase-transition after FUS exposure. Moreover, the combined treatment of A-DPPs nanoparticles with FUS exhibited significantly higher apoptosis rate, stronger inhibitory effect on 4T1 cell invasion in vitro, induced more reactive oxygen species (ROS), and enhanced anti-tumor effect compared to a single therapy (p < 0.05). Additionally, the joint strategy resulted in more intense cavitation effect and larger ablated areas and reduced energy efficiency factor (EEF) both in vitro and in vivo.Conclusion The multifunctional AS1411-DOX/PFH-PEG@PLGA nanoparticles can perform as a marvelous synergistic agent for enhanced FUS/chemotherapy, promote real-time contrast enhanced US imaging and improve the therapeutic efficacy and prognosis of TNBC.
研究领域:
肿瘤学
·
纳米技术
·
医学影像
·
癌症治疗
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Lin Liu,Junpeng Shi,Jinyuan Wang,Linping He,Yan Gao,Peng Lin,Yutong Han,Ping'an Ma,Jun Lin,Yun Zhang
Pyroptosis possesses potent antitumor immune activity, making pyroptosis inducer development a promising direction for tumor immunotherapy. Persistent luminescence nanoparticles (PLNPs) are highly sensitive optical probes extensively employed in tumor diagnosis and therapy. However, a pyroptosis inducer based on PLNPs has not been reported yet. Herein, polyethylene glycol–poly lactic acid-co-glycolic acid (PEG–PLGA: PP) modified biodegradable CaS:Eu 2+ (CSE@PP) PLNPs are synthesized as a pyroptosis inducer for tumor immunotherapy for the first time. The synthesized CSE@PP possesses biowindow persistent luminescence (PersL) and pH-responsive degradation properties, allowing it to remain stable under neutral pH but degrade when exposed to weak acid (pH < 6.5). During degradation within the tumor, CSE@PP constantly releases H 2 S and Ca 2+ while its PersL gradually fades away. Thus, the PersL signal can self-monitor H 2 S and Ca 2+ release. Furthermore, the released H 2 S and Ca 2+ result in mitochondrial dysfunction and the inactivation of reactive oxygen species scavenging enzymes, synergistic facilitating intracellular oxidative stress, which induces caspase-1/GSDM-D dependent pyroptosis and subsequent antitumor immune responses. In a word, it is confirmed that CSE@PP can self-monitor H 2 S and Ca 2+ release and pyroptosis-mediated tumor Immunotherapy. This work will facilitate biomedical applications of PLNPs and inspire pyroptosis-induced tumor immunotherapy.
研究领域:
纳米技术
·
生物医学工程
·
癌症研究
·
免疫治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2019
·Vol. 11
·期 27
·13126-13138
·
IF 6.97
Yurui Zhou,Lu Li,Shenghui Li,Shufei Li,Miao Zhao,Qinghong Zhou,Xiaoqun Gong,Jin Yang,Jin Chang
Diabetic cataracts (DCs) are one of the most common ocular complications of diabetes, and easily causes blindness among diabetics. However, there are limited drugs to delay and prevent DCs. Research studies indicate that oxidative damage of the crystalline lens and nonenzymatic glycosylation of the lens protein play a key role in the pathogenesis of DCs. Hence, we developed a kind of autoregenerative redox nanoparticle, which was CeO2 NPs coated with PEG-PLGA (PCNPs). We first found that PCNPs could work not only as an antioxidant to protect lens epithelial cells from oxidative stress based on the repetitive elimination of reactive oxygen species (ROS), but also as a glycation inhibitor effectively restraining α-crystallin glycation and crosslinking, thereby keeping the lens transparent and alleviating DCs. Experimental results successfully validated the fact that the PCNPs were able to operate in eyes for a long time to attenuate lens opacity. We expect that this strategy will provide promising potential for the treatment of DCs.
研究领域:
药理学
·
眼科学
·
纳米技术
·
糖尿病研究
✓ 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）