CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Chengxiu Wei,Chuangang You,Liming Zhou,Huiling Liu,Shihao Zhou,Xingang Wang,Rui Guo
Excessive scar formation has severe physiological and psychological effects on patients, and tissue restoration to functioning without scar generation after wounding continues to be a significant challenge. Yes-associated protein (YAP) is a downstream effector of the Hippo pathway that interacts with the transcriptional-enhanced associate domain to regulate stem cell proliferation, tissue growth, and organ size. Blocking mechanotransduction signaling can reduce tissue fibrosis and scar formation. This study developed a biocompatible detachable hydrogel microneedle (MN) system for scarless wound healing. The photosensitizing drug bismuth nanosheets (Bi) and YAP signaling pathway inhibitor verteporfin (Vp) were integrated into the pyramidal MN array. The MN system has sufficient mechanical strength to penetrate the skin, after the separable connection degrades, the tips can be left inside the tissue for continuous active release, and the substrate can be removed safely. The study shows that inhibition of YAP signaling encouraged scar-free wound healing without fibrosis and with the regeneration of secondary skin elements (hair follicles, sebaceous glands). Therefore, MN can serve as an excellent drug delivery system and will have numerous practical benefits in scar-free wound regeneration.
研究领域:
生物材料学
·
再生医学
·
药理学
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DOI
高影响因子
Small Methods
·
2023
·
IF 12.4
Peng Wang,Zhangwen Peng,Liu Yu,Yiling Liu,Hanwen Wang,Ziheng Zhou,Hengdeng Liu,Sheng Hong,Yichu Nie,Yang Deng,Yang Liu,Julin Xie
Hypertrophic scarring (HS) is a common skin injury complication with unmet needs. Verteporfin (VP) should be an ideal HS-targeted therapeutic drug due to its efficient fibrosis and angiogenesis inhibitory abilities. However, its application is restricted by its side effects such as dose-dependent cytotoxicity on normal cells. Herein, the bioadhesive nanoparticles encapsulated VP (VP/BNPs) are successfully developed to attenuate the side effects of VP and enhance its HS inhibition effects by limiting VP releasing slowly and stably in the lesion site but not diffusing easily to normal tissues. VP/BNPs displayed significant inhibition on the proliferation, migration, collagen deposition, and vessel formation of human hypertrophic scar fibroblasts (HSFBs) and dermal vascular endothelial cells (HDVECs). In a rat tail HS model, VP/BNPs treated HS exhibits dramatic scar repression with almost no side effects compared with free VP or VP-loaded non-bioadhesive nanoparticles (VP/NNPs) administration. Further immunofluorescence analysis on scar tissue serial sections validated VP/BNPs effectively inhibited the collagen deposition and angiogenesis by firmly confined in the scar tissue and persistently releasing VP targeted to nucleus Yes-associated protein (nYAP) of HSFBs and HDVECs. These findings collectively suggest that VP/BNPs can be a promising and technically advantageous agent for HS therapies.
研究领域:
药学
·
生物医学工程
·
皮肤科学
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DOI
PubMed
高影响因子
RSC Advances
·
2016
·Vol. 6
·期 103
·100984-100992
·
IF 3.289
Mengshi Yang,Di Jiang,Zhilong Chen,Jun Chen
Photodynamic therapy (PDT) does well in both curing early stage tumors and improving patients’ quality of life. However, the limited selectivity of photosensitizers (PSs) to tumors has become an urgent issue during the application of PDT clinically, which would exhibit a poor therapeutic outcome and induce skin phototoxicity. To solve this problem, PS-loaded D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS, or simply TPGS) nanoparticles with tumor homing and penetrating peptide tLyp-1 decoration (t-NP) were constructed for PDT of tumors in this study. Verteporfin (VP), as an effective PS, was encapsulated in the core of t-NP, and tLyp-1 was functionalized on the surface as a functional ligand to increase vascular permeability and target the tumor cells. These nanoparticles were spherical in shape and exhibited a narrow size distribution of 23.3 ± 0.80 nm, and had a high encapsulation efficiency and loading capacity of hydrophobic VP. Compared with unmodified nanoparticles (NP), t-NP exhibited enhanced cellular uptake in both primary human umbilical vein endothelial cells (HUVECs) and drug-resistant human colon adenocarcinoma cells (HCT15); and t-NP showed higher selectivity to HCT15 tumors in vivo after intravenous administration of the same dose of VP. The anti-tumor experiment in vivo strongly indicated that nanoparticles with tLyp-1 peptide modification can enhance the selectivity of the PS, and improve the PDT effect.
研究领域:
药剂学
·
肿瘤学
·
纳米医学
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DOI
高影响因子
MATERIALS & DESIGN
·
2023
·
IF 8.4
Xingyu Ouyang,Wei Yu,Jianguang Wang,Hui Wang,Shikun Wang,Gang Wang,Baifeng Sun,Xu Chen,Yang Liu,Wei Wang,Cunyi Fan
Peritendinous adhesion is one of the most common postoperative or posttraumatic complications of tendon injury, which severely limits functional rehabilitation and raises the risk of re-rupture. This study prepared a multifunctional composite composed of a “sandwich” electrospun nanofibrous membrane with sustained drug release property and adhesives for sutureless application. The composite was assessed here through microscopic, spectroscopic, wettability, rheological, mechanical, and drug release analyses. The results of these characterizations are consistent with the characteristics of anti-adhesion biomaterials. In addition, the anti-adhesion effectiveness was demonstrated in fibroblasts and rats. Briefly, the composite not only decreased the proliferation, viability, and penetration of fibroblasts but also repressed cell spreading on the material surface by regulating Yes-associated protein (YAP) and inhibited oxidative stress by scavenging reactive oxygen species (ROS) simultaneously in vitro. Meanwhile, histological analysis, functional tests, gross observation, and protein analysis in vivo showed that composite was effective in reducing tendon adhesion formation. Hence, we draw the conclusion that our composite can protect tendons from peritendinous adhesion after injury and provide a new direction for future application of peritendinous anti-adhesion.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
药剂学
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Xiaorong Gou,Jiayi Li,Qianyuan Yu,Xinxin Hao,Shiyu Li,Yiyi Zhang,Hong Deng,Hua Guo,Xue Yang,Weiqi Zhang
Trehalose (Tr) is a naturally occurring disaccharide extensively used as a stabilizing and cryoprotective agent for protein and cell preservation. Owing to its unique bioactivities, Tr-based biomaterials have recently emerged as a promising class of functional materials for biomedical applications. In this work, we reveal that Tr can protect lysosomes from the damage caused by verteporfin (VP), a clinically used photosensitizer. Inspired by this finding, a Tr nanogel (NG) ionically crosslinked with ferric ion was designed for the enhanced photodynamic therapy (PDT) of VP using a murine 4T1 breast cancer model. The constructed Tr/VP NG demonstrates a hydrodynamic diameter of 157.1 ± 2.8 nm, effective cellular uptake and a light-induced reactive oxygen species (ROS) generation in cells. Compared with free VP, the Tr/VP NG exhibits a comparable phototoxicity but with relieved dark toxicity in vitro , which could be evidenced by a less lysosomal leakage in cells and a lower hemolytic activity. Moreover, the Tr/VP NG mediates an elongated tumor accumulation of VP and meanwhile significantly improves antitumor PDT efficacy in vivo . This Tr/VP NG highlights both the feasibility of lysosome protection to minimize undesired dark toxicity of VP and a facile approach for engineering Tr-based materials.
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DOI
PubMed
高影响因子
Journal of Bionic Engineering
·
2024
·
IF 4.9
Jiao Tian,Zhou Ruilu,Jiao Junrong,Jiao Junna,Lian Qin
The shortage of transplantable skin is the leading cause of death in patients with extensive skin defect. Addressing this challenge urgently requires the development of skin substitutes capable of wound repair and facilitating skin regeneration. In this study, a biomimetic bilayer skin tissue model consisting of collagen, gelatin/sodium alginate, fibroblasts, human umbilical vein endothelial cells, keratinocytes, melanocytes, and verteporfin was devised. Then, the skin model was fabricated using precise extrusion/inkjet bioprinters, and it reconstruction capabilities were evaluated through skin defect repair experiments. The printed skin tissue reduced the inflammatory response of the wound by 38% and inhibited the expression of TGF-β and YAP, and promoted the transformation of macrophages from M1 phenotype to M2 phenotype, thus promoting the reasonable reconstruction of fibronectin and collagen on the wound, finally promoting the wound healing, and reducing the wound contraction and scar formation. In addition, the proliferation and differentiation of human umbilical vein endothelial cells, keratinocytes, and melanocytes in printed skin increased the number of regenerated blood vessels by 123%, while promoting the reconstruction of multilayer epidermal structure and skin color. The outcomes of this investigation present a promising skin model and therapeutic strategy for skin injury, offering a potential avenue for the reconstruction of skin structure and function.
研究领域:
生物打印
·
组织工程
·
伤口愈合
·
再生医学
·
生物材料
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DOI
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-16
·
IF 10.6
Qi Ji,Zhang Long,Ren Zhongyu,Yuan Yi,Yu Jiahao,Zhang Yining,Gu Linbo,Wang Xu,Wang Yan,Xu Haoyue,Yu Rutong,Zhou Xiuping
Background The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. Results In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent blood‒brain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. Conclusion Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.
研究领域:
肿瘤学
·
药学
·
分子生物学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2026
·Vol. 16
·期 5
·2372
·
IF 13.3
Jiawen Chen,Junfeng Liu,Xiaoting Zhang,Xi Li,Jinming Fan,Shengchao Zhao,Junbin Liu,Bin Zhou,Ke Zhang
Background: Hepatocellular carcinoma (HCC), the major form of primary liver cancer, contributes markedly to cancer-related mortality worldwide and remains a serious global health concern, particularly affecting individuals with underlying chronic liver disorders. In hepatocellular carcinoma, insufficient radiofrequency ablation (iRFA) has been reported to drive local tumor relapse and distant spread, possibly by aggravating the immunosuppressive features of the tumor microenvironment. The present work seeks to clarify the underlying pathways driving the development of an immunosuppressive milieu after RFA and to identify potential therapeutic approaches to counteract this process. Methods: An injectable hydrogel composed of quaternized chitosan (QCS) and tannic acid (TA) was constructed to encapsulate verteporfin (VP), a well-established photosensitizer that has been clinically applied for treating neovascular retinal disorders such as age-related macular disease. Beyond its ophthalmologic application, VP has recently been reported to display anti-tumor activity through inhibition of oncogenic regulators such as Yes-associated protein (YAP), indicating its potential utility in cancer therapy. This hydrogel formulation is designed to target residual tumor tissue post-RFA, providing localized delivery and sustained release of VP to enhance anti-tumor immune responses. Results: Our findings identified YAP activation as a critical mediator of immunosuppression in residual tumors following RFA. Pharmacological inhibition of YAP significantly reduced the infiltration of myeloid-derived suppressor cells (MDSCs) and effectively reversed the immunosuppressive microenvironment conditions. Furthermore, the QCS/TA hydrogel enabled sustained local release of VP, resulting in enhanced antitumor immune responses via MDSC suppression. When administered as an adjuvant therapy following suboptimal RFA, the hydrogel markedly inhibited the progression of residual tumors, highlighting its therapeutic potential in improving post-RFA outcomes. Conclusion: Collectively, our data suggest YAP pathway inhibition as a promising immunomodulatory strategy to complement RFA in HCC management. This work demonstrates that the QCS/TA hydrogel-based delivery system can remodel the tumor immune milieu to overcome immunosuppression and delay post-ablation tumor recurrence, supporting its potential as a translational drug delivery strategy.
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PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2026
·
IF 4.9
Wei Mingli,Chu Chenxiao,Ding Huaiwei,Zhao Jiansong,Ji Muse,Liang Xinxin,Bi Xiaoshuang,Zhao Jiaqi,Gou Jingxin,Yin Tian,He Haibing,Tang Xing,Zhang Yan,Zhang Yu
Cabazitaxel (CTX) exhibits potent antineoplastic activity
and is
demonstrated to promote antitumor immunity by triggering immunogenic
cell death (ICD). This is commonly used in the clinical treatment
of advanced and metastatic triple-negative breast cancer (TNBC). However,
the therapeutic index of commercial CTX injections is severely restricted
by their definite systemic toxicity and low tolerability. Herein,
we developed biomimetic low-density lipoprotein nanoparticles (CTX 2 TK&VP@LDL NPs) by integrating ROS-responsive CTX dimeric
prodrugs (CTX 2 TK) and the photosensitizer verteporfin (VP)
into LDL NPs to selectively target tumors and achieve synergistic
chemophotodynamic therapy and immunotherapy for TNBC with improved
biosafety. CTX 2 TK&VP@LDL NPs were able to enhance the
accumulation and cellular uptake in 4T1 tumors overexpressing LDL
receptor, improving the targeted codelivery efficiency. When CTX 2 TK&VP@LDL NPs were deposited at the tumor sites, localized 1 O 2 was generated upon irradiation for triggering
ultrafast CTX release with low premature CTX leakage in the off-target
tissue. Additionally, the generated 1 O 2 can
further synergistically reinforce ICD and elicit robust antitumor
immune activation. The combination treatment with CTX 2 TK&VP@LDL
NPs and PD-L1 blockade notably inhibited abscopal tumor growth and
lung metastasis. Taken together, the biomimetic CTX 2 TK&VP@LDL
NPs exploit endogenous LDL functionality to enable receptor-mediated
tumor targeting and synergistic chemophotodynamic immune activation,
providing an effective and safe therapeutic strategy for TNBC.
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高影响因子
NANOTECHNOLOGY
·
2026
·Vol. 37
·期 20
·205101
·
IF 2.9
Qian-Qian Ma,Ling Wang,Si-Yuan Zhou,Bang-Le Zhang,Li- Shuang Hou
The mechanical traction caused by high cross-linking extracellular matrix (ECM) can promote the continuous activation of hepatic stellate cells (HSCs) by yes-associated protein (YAP)-mediated mechanical signal. Therefore, targeted inhibiting the activation of HSCs induced by mechanical traction is the main measure to improve liver fibrosis. The activated HSCs (aHSCs)-targeted drug delivery nanosystem of verteporfin@polyethyleneimine-vitamin A (VP@PSA), which loaded VP a small molecule inhibitor of YAP in the Hippo signaling pathway to regulate mechanical signal transduction was constructed. The particle size of VP@PSA was 167.1 ± 1.5 nm with great stability, and the drug loading of VP was 34.39 ± 2.41% and encapsulation efficiency was 93.28 ± 1.57%. The targeting and therapeutic effect of VP@PSA were verified by immunofluorescence, flow cytometry and competitive inhibition experiments. The biocompatibility was evaluated by hemolysis, pyrogen, vascular stimulation, respiration and behavior. Compared with non-targeted delivery system, VP@PSA showed best targeting ability to aHSCs among different kinds of liver cells. VP@PSA had an excellent therapeutic effect on suppressing the activation of HSCs, reducing ECM deposition and improving liver fibrosis by regulating YAP/ lysyl oxidase like 2/connective tissue growth factor signal in vitro and in vivo. Furthermore, VP@PSA had favorable biological safety and no toxicity to the main organs. The constructed VP@PSA delivery system laid a solid theoretical and experimental foundation for developing clinical targeted drugs for liver fibrosis.
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PubMed
高影响因子
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