ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Wenxiong Cao,Yuan Liu,Pan Ran,Jie He,Shuang Xie,Jie Weng,Xiaohong Li
Antithrombosis therapy is confronted with short half-lives of thrombolytic agents, limited therapeutic effects, and bleeding complications. Drug delivery systems of thrombolytic agents face challenges in effective penetration into thrombi, which are characterized by well-organized fibrin filled with abundant activated platelets. Herein, Janus rod (JR)-shaped micromotors are constructed by side-by-side electrospinning and cryosection, possessing advantages in controlling the Janus structure and aspect ratio of microrods. Silicon phthalocyanine (Pc) and CaO2 nanoparticles (NPs) are loaded into the separate sides of JRs, and Arg-Gly-Asp (RGD) peptides are grafted on the surface to obtain Pc/Ca@r-JRs for the sonodynamic therapy (SDT) of thrombosis without using any thrombolytic agents. Decomposition of CaO2 NPs ejects O2 bubbles from one side of JRs, and ultrasonication of O2 bubbles produces the cavitation effect, both generating mechanical force to drive the thrombus penetration. The integration of ultrasonication-propelled motion and RGD mediation effectively increases the targeting capabilities of r-JRs to activated platelets. In addition to mechanical thrombolysis, ultrasonication of the released Pc produces 1O2 to destruct fibrin networks of clots. In vitro thrombolysis of whole blood clots shows that ultrasonication of Pc/Ca@r-JRs has a significantly higher thrombolysis rate (73.6%) than those without propelled motion or RGD-mediated clot targeting. In a lower limb thrombosis model, intravenous administration of Pc/Ca@r-JRs indicates 3.4-fold higher accumulations at the clot site than those of JRs, and ultrasonication-propelled motion further increases thrombus retention 2.1 times. Treatment with Pc/Ca@r-JRs and ultrasonication fully removes thrombi and significantly prolongs tail bleeding time. Thus, this study has achieved precise and prompt thrombolysis through selective targeting to clots, efficient penetration into dense networks of thrombi, and SDT-executed thrombolysis.
研究领域:
生物医学工程
·
治疗学
·
纳米技术
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Polymer Materials
·
2025
·
IF 4.7
Jinxuan He,Zhixiang Mou,Lan Chen,Qixian Chen,Xuduan Chen,Lixin Wei
Secondary hyperparathyroidism is driven by pathological overproduction of parathyroid hormone. Surgery is invasive, drug therapy offers only transient control, and both carry substantial side effects. Previous efforts to deliver siRNA to the parathyroid glands achieved only marginal efficacy because the constructs lacked a targeting ligand to overcome the organ’s limited vascular permeability and were rapidly cleared by renal filtration. This study provides a targeted RNA interference therapeutic strategy for treatment of secondary hyperparathyroidism by leveraging the angiogenic characteristics of parathyroid glands via systemic route. Particularly, we manufactured an Arg-Gyl-Asp (RGD)-conjugated siRNA delivery system that exploits the overexpression of integrins and increased vascular permeability in parathyroid glands to achieve preferential siRNA accumulation. The multifunctional cationic copolymers of RGD-poly(ethylene glycol) (PEG)-polylysine-azido [PLys(N3)] and PLys(ss-dibenzocyclooctyne: DBCO) were synthesized and characterized, demonstrating their ability to formulate robust nanocomplexes with small interference RNA [(siRNA): knockdown of parathyroid hormone (PTH)] by virtue of favorable reversible disulfide cross-linking (based on click reaction) post electrostatic complexation. These nanocomplexes exhibited prolonged systemic circulation, preferential accumulation in the angiogenic parathyroid glands, and active intracellular delivery, leading to significant suppression of PTH expression. In a parathyroid hyperplasia mouse model, the siPTH delivery construct from RGD–PEG-PLys(N3)&PLys(ss-DBCO) substantially reduced the serum PTH levels to near-normal values, highlighting the therapeutic potential of our siRNA delivery system. Hence, this RNAi approach outperforms conventional modalities by achieving rapid, potent, and sustained gene knockdown without surgical risk or chronic pharmacologic burden, establishing a paradigm for precision endocrine therapy.
研究领域:
分子生物学
·
内分泌学
·
纳米医学
·
基因治疗
·
药理学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Gang Pan,Ting-ting Jia,Qian-xia Huang,Yan-yan Qiu,Jie Xu,Pei-hao Yin,Tao Liu
Novel methods to improve the anticancer performance of 5-fluorouracil (5-FU) is quite necessary for clinical medicines. In the present work, we fabricated a novel type of mesoporous silica nanoparticles (MSNs)-based inorganic/organic hybrid nanoparticles covalently attached with poly(oligo(ethylene glycol) monomethyl ether methacrylate) (POEGMA) for improved stabilization and targeting peptide (RGD) for targeted delivery with the aim of improving the anticancer performance of 5-FU. Atom transfer radical polymerization (ATRP) initiator functionalized MSN (MSN-Br) was synthesized at first, which was followed by surface-initiated ATRP of water soluble OEGMA and carboxyl-containing monomer (2-succinyloxyethyl methacrylate, SEMA). Functionalization of RGD onto the hydrophilic P(OEGMA- co -SEMA) chains afforded the final hybrid nanoparticle, MSN-P(OEGMA- co -RGD). 5-FU can be effectively loaded into the meso -pores of MSN-P(OEGMA-c o -RGD) ( [email protected] ) with drug content ∼7.5 wt%. And the dynamic diameter ( D h ) and zeta potential (ζ) of [email protected] were determined to be 199.3 ± 5.4 nm and −8.7 ± 0.5 mV, respectively. It was demonstrated that MSN-P(OEGMA-c o -RGD) exhibited improved internalization into colon cancer cells and enhanced accumulation in tumor tissues. In addition, compared with free 5-FU, [email protected] showed enhanced anticancer efficacy both in vitro and in vivo, implying promising clinical applications.
研究领域:
纳米医学
·
癌症治疗
·
药物递送系统
·
材料科学
·
聚合物化学
✓ 已验证
DOI
PubMed
高影响因子
MICROSCOPY RESEARCH AND TECHNIQUE
·
2021
·Vol. 85
·期 4
·1518-1526
·
IF 2.769
Leilei Hong,Lichan Yuan,Xiaoxu Xu,Yuhuan Ma,Li Meng,Junyi Wang,Na Zhao,Xiaoliang Wang,Junqing Ma
Titanium (Ti) alloys, particularly Ti 6 Al 4 V, are the most commonly used biomedical implant material. Ti alloys are biologically inert, so there have been continuous efforts to improve their osteogenic properties and clinical performance. Since TiO 2 nanotubes (NT) appear to be excellent drug platforms, and strontium reportedly enhances osteogenesis, we constructed a TiO 2 nanotube coating on the surface of Ti 6 Al 4 V and immersed it in Sr (OH) 2 solution in order to incorporate Sr into TiO 2 nanotubes (NT-Sr). The results of field emission scanning electron microscope and X-ray diffraction analysis verified the fabrication of NT-Sr. We next added polydopamine (PDA) and cyclo- (arginine–glycine–aspartic acid–phenylalanine–cysteine) [c(RGDfC)] peptides to further promote biocompatibility of the implant. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy confirmed the existence of PDA and c(RGDfC). Mesenchymal stem cells (MSCs) were planted on Ti, NT, NT-Sr, NT-Sr/PDA, and NT-Sr/PDA-RGD surfaces. The adhesion and differentiation of MSCs on different surfaces were evaluated. The mRNA expression of alkaline phosphatase, runt-related transcription factor 2 (Runx2) and type I collagen (Col I) of different groups were also tested. Finally, we observed that the NT-Sr/PDA-RGD group showed significantly better performance than other groups in terms of the differentiation and osteogenesis-related gene expression of MSCs. Thus, the NT-Sr/PDA-RGD complex may be an important modification strategy for Ti, as it shows excellent osteogenic potential.
研究领域:
生物材料
·
组织工程
·
骨科
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2023
·
IF 5.8
Wenbo Wang,Shihao Zhou,Zhaoyi Cheng,Dong Ma,Tao Liu
CRISPR-Cas9 technology has been proven to be the most straightforward and accurate tool for gene therapy, but some limitations, such as the inefficient transfection or inability to precisely target, prevent the gene therapy from achieving the desired therapeutic effect. To overcome these, a kind of glutathione-sensitive cationic vectors, hyperbranched polyamide amine (HPAA) was designed for Delivery of CRISPR-Cas9 RNA plasmid, and the cyclic RGD (Arg-Gly-Asp) was conjugated for the targeted treatment of nasopharyngeal carcinoma (NPC). Disulfide bonds in HPAA segments can specifically respond to the high glutathione concentration in the tumor microenvironment. Meanwhile, RGD could especially interact to the integrin α v β 3 receptors which are highly expressed on the surface of NPC tumor cells. The results showed that more HPAA-RGD/SGK3-gRNA complexes could be uptaken by NPC HNE-1 cells after RGD was conjugated, and then the plasmid could be accumulated in the NPC tumor as well, which may assure the satisfied NPC therapy effect in vivo. In transfection assays, this complex showed the acceptable gene transfection efficiency in vitro and the obvious tumor inhibition effect in vivo, suggested a potential application in gene therapy to NPC.
研究领域:
分子生物学
·
基因治疗
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Physical Chemistry Letters
·
2024
·
IF 4.8
Zhiyu Wu,Cong Wang,Chen Li,Nan Xu,Xiaoyong Cao,Shengfu Chen,Yao Shi,Yi He,Peng Zhang,Jian Ji
Cell adhesion peptides (CAPs) often play a critical role in tissue engineering research. However, the discovery of novel CAPs for diverse applications remains a challenging and time-intensive process. This study presents an efficient computational pipeline integrating sequence embeddings, binding predictors, and molecular dynamics simulations to expedite the discovery of new CAPs. A Pro2vec model, trained on vast CAP data sets, was built to identify RGD-similar tripeptide candidates. These candidates were further evaluated for their binding affinity with integrin receptors using the Mutabind2 machine learning model. Additionally, molecular dynamics simulations were applied to model receptor–peptide interactions and calculate their binding free energies, providing a quantitative assessment of the binding strength for further screening. The resulting peptide demonstrated performance comparable to that of RGD in endothelial cell adhesion and spreading experimental assays, validating the efficacy of the integrated computational pipeline.
研究领域:
计算生物学
·
生物信息学
·
组织工程
·
肽类发现
·
分子建模
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2015
·Vol. 25
·期 47
·7317-7326
·
IF 11.805
Shi-Ying Li,Li-Han Liu,Lei Rong,Wen-Xiu Qiu,Hui-Zhen Jia,Bin Li,Fei Li,Xian-Zheng Zhang
A dual-Förster resonance energy transfer (FRET)-based versatile prodrug (V-prodrug), in which the fluorescence of both 5(6)-carboxylfluorescein (FAM) and doxorubicin (DOX) can be quenched by 4-(dimethylaminoazo)benzene-4-carboxylic acid (Dabcyl) with high quenching efficiency, is developed in this paper. The V-prodrug can selectively bind to the α v β 3 integrin overexpressed cancer cells through the Arg-Gly-Asp (RGD) targeting moiety. After that, the acid-mediated DOX release of the V-prodrug can be real-time monitored by the increase of the red fluorescence from DOX. Thereafter, DOX-induced cell apoptosis can also be in situ assessed by the fluorescence recovery of the FAM, due to the caspase-3-mediated Asp-Glu-Val-Asp (DEVD) peptide sequence cleavage. This novel prodrug provides a cascaded imaging of real-time drug release and subsequent cell apoptosis, which enables the in situ detection of the cancer response and the therapeutic efficacy evaluation of the prodrug.
研究领域:
药理学
·
生物医学工程
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DRUG TARGETING
·
2018
·
IF 3.408
Bohui Xu,Yan Xu,Gaoxing Su,Hongyan Zhu,Li Zong
Successful delivery of small interfering RNA (siRNA) into the cytoplasm of target cells relies on biocompatible and efficient vectors. In this study, a novel multifunctional core/shell nanoparticle [CS-SS-9R/BSA-c(RGDyK)] was developed to effectively deliver siVEGF to hepatocellular carcinoma cells (Bel-7402 cells). To improve the gene payload and transfection efficiency, a positively charged inner core (CS-SS-9R) was constructed by grafting nona-arginine (9R) onto chitosan (CS) using disulphide bonds. The negatively charged outer shell [BSA-c(RGDyK)] assembled on the surface of the inner core by electrostatic forces that shielded high cationic charges and provided improved targeting. The protein outer shell gradually detached from the inner core in the acidic lysosomal environment, leaving the cationic inner core exposed in order to escape from lysosomes. The nanoparticles were capable of delivering siVEGF into Bel-7402 cells via integrin receptor-mediated endocytosis. Successful lysosomal escape of the inner core and the rapid release of siVEGF into the cytoplasm resulted in a 78.9% decrease in VEGF expression and 81.2% inhibition of tumour cell proliferation. In conclusion, this nanoparticle is responsive to the intracellular environment and accurately delivered siRNA into the cytoplasm, providing a safe and highly efficient gene delivery strategy for cancer therapy.
研究领域:
纳米技术
·
癌症生物学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2021
·Vol. 10
·期 3
·384-395
·
IF 6.331
Juan Liu,Xixue Hu,Shubin Jin,Xing-Jie Liang,Xiaowei Ma
Rapid release and clearance of antitumor drugs in vivo are the main factors used to evade the effectiveness of chemotherapeutics. Targeted delivery and controlled release of drugs are the most pressing dilemmas in cancer therapy. Herein we report the design and fabrication of multifunctional mesoporous silica nanoparticles coated with poly(N-isopropylacrylamide)-co-acrylic acid and calcium phosphate (MSCNs) with pH-triggered chemotherapeutic release and dual-targeting functions. By decorating the nanoparticle surface with a transferrin (Tf)/RGD ligand, these nanoparticles are capable of not only recognizing the intrinsic pH difference between tumor and normal tissues, but also targeting the lesion location. It was shown that Tf/RGD-MSCNs delivered the anti-tumor drug doxorubicin more efficiently into lysosomes and the resulting DOX-loaded nanoparticles (DOX-Tf/RGD-MSCNs) showed a stronger inhibitory effect towards tumor cell growth than free DOX and DOX delivered by unmodified MSNs. Moreover, the nanoparticles are more biocompatible than uncoated mesoporous silica nanoparticles. All these results indicate that Tf/RGD-MSCNs have great potential as a novel drug carrier in therapeutic applications against cancers.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2021
·
IF 6.419
Jiachi Ma,Yuzhong Chen,Wanqing Liang,Lei Li,Jun Du,Chengwu Pan,Chensong Zhang
Gastric cancer (GC) remains a major public health problem. Ursolic acid (UA) is reported to be effective in inhibiting GC; however, its low solubility and poor biocompatibility have greatly hindered its clinical application. Herein, an innovative reactive oxygen species (ROS)-sensitive UA dimeric prodrug is developed by coupling two UA molecules via a ROS-cleavable linkage, which can self-assemble into stable nanoparticles in the presence of surfactant. This new UA-based delivery system comprises the following major components: (I) dimeric prodrug inner core that can achieve high drug-loading (55%, w/w) and undergo rapid and selective conversion into intact drug molecules in response to ROS; (II) a polyethylene glycol (PEG) shell to improve colloid stability and extend blood circulation, and (III) surface-modified internalizing RGD (iRGD) to increase tumor targeting. Enhancement of the antitumor effect of this delivery system was demonstrated against GC tumors in vitro and in vivo. This novel approach offers the potential for clinical applications of UA.
研究领域:
药学
·
纳米技术
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Shumiao Tian,Tao Jiang,Min Su,Peixue Su,Zhekun Jia,Lang Ke,Yuhang Cheng,Yuxin Cao,Gang Liu,Chengchao Chu,Junxue Gao
In recent years, issues such as heterogeneity, drug resistance, recurrence and metastasis, as well as the side effects of treatment have made breast cancer treatment complex and challenging. To fulfill the pressing demand for efficient sonodynamic therapy (SDT), a strategy was devised to combine carbon monoxide with chemotherapeutic agents, resulting in a novel sonotherapy agent. This study introduces a new type of porphyrin-based nano-sonosensitizer, R-TDM, synthesized through coordination chemistry. The coordination nanoparticles, facilitate fluorescence (FL) and magnetic resonance imaging, enhancing dynamic treatment by increasing reactive oxygen species (ROS) production and allowing controlled release of carbon monoxide (CO) under ultrasound stimulation. More importantly, concomitant with the release of CO, the in-situ derived novel chemotherapeutic agent, Mn-bpy, will further damage the DNA of tumor cells, enabling sustained chemotherapy (CT) post-ultrasound. Furthermore, the cell membrane coating, modified with the Arg-Gly-Asp peptide (RGD), actively targets tumor sites while improving biocompatibility. This innovation paves the way for the development of multifunctional sonotherapy diagnostics, addressing the clinical challenges associated with SDT.
研究领域:
纳米医学
·
肿瘤治疗
·
生物无机化学
·
医学影像
·
药物递送
·
分子成像
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 29
·期 36
·1904056
·
IF 15.621
Jing Zhu,Chengchao Chu,Dongsheng Li,Xin Pang,Huili Zheng,Junqing Wang,Yesi Shi,Yang Zhang,Yi Cheng,En Ren,Jingliang Cheng,Xiaoyuan Chen,Gang Liu
To address the urgent need for effective sonodynamic therapy (SDT), a facile and efficient strategy is developed for fabricating a new class of sonotheranostics. Herein, a Fe(III)-porphyrin nano-sonosensitizer is prepared by a one-step coordination synthesis, and then anchored with Bis(DPA-Zn)-RGD and manganese superoxide dismutase (SOD2) siRNA. Benefiting from the delicate interactions of the Fe(III)-coordinated nanoformulations, a highly potent sono/gene combinational therapy guided by fluorescence/magnetic resonance imaging is achieved. Importantly, this sonotheranostics significantly enhances the SDT effect of porphyrin through the cancer-targeted delivery capability and enhanced reactive oxygen species production via triple-regulated approaches, including down-regulation of SOD2, depletion of glutathione, and generation of Fenton reaction. This work opens up new perspectives for developing versatile sonotheranostics to overcome the clinical challenges of SDT.
研究领域:
纳米技术
·
癌症研究
·
诊疗学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）