POLYMER SCIENCE SERIES A
·
2021
·Vol. 63
·期 6
·769-778
·
IF 1.206
Yu Lili,Yao Lin,Yang Kuan,Fei Wenling,Chen Qingqing,Qin Lan,Liu Shaojing,Zou Zengqiang,Qin Bei
Abstract The surface cRGD modified polymeric (PMMA- b -PPEGMA-RGD) micelles were constructed by a combination of two-step atom transfer radical polymerization (ATRP), azide reaction, click reaction, deprotection, self-assembly of amphiphilic polymers, and addition reaction. The self-assembled DOX-loaded micelles had spherical morphology. The average size of DOX-loaded micelles measured by scanning electron microscopy (SEM) and dynamic light scattering (DLS) was less than 200 nm. According to the enhanced permeability and retention (EPR) effect of solid tumors, the micelles should have the passive targeting of tumor tissues. The introduction of cRGD on the micelles surface can not only achieve the active targeting of drug carriers to tumor tissues, but also form the network hydrogen bond between the PEG unit at the hydrophilic end of the micelles and the guanidine group in RGD, to improve the uniformity of the particle size distribution and the stability of drug loading, and also achieve the slow release of drugs. The cytotoxicity of DOX-loaded micelles on SGC7901 cells in vitro indicated that PMMA- b -PPEGMA-RGD micelles could provide the same or more remarkable antitumor activity (at low dose) as DOX. The results showed that PMMA- b -PPEGMA-RGD micelles might have great potential applications in the delivery of hydrophobic anticancer drugs.
研究领域:
药剂学
·
聚合物化学
·
药物递送系统
·
癌症研究
✓ 已验证
DOI
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2024
·
IF 2.6
Zhicheng Zhang,Xin Wang,Qi Dai,Yaxin Qin,Xiaoyan Sun,Minoru Suzuki,Xiaoying Ying,Min Han,Qichun Wei
Glioblastoma is a highly aggressive glioma with limited treatment options. Boron neutron capture therapy (BNCT) offers a promising approach for refractory cancers, utilizing boron-10 (10B) and thermal neutrons to generate cytotoxic particles. Effective BNCT depends on selective targeting and retention of 10B in tumors. Current BNCT drugs face issues with rapid clearance and poor tumor accumulation. To address this, we developed gold nanoparticles (AuNPs) functionalized with cyclic arginine-glycine-aspartic acid (cRGD) peptides as a nanocarrier for Sodium Mercaptododecaborate (BSH), resulting in AuNPs-BSH&PEG-cRGD. In vitro, AuNPs-BSH&PEG-cRGD increased 10B content in GL261 glioma cells by approximately 2.5-fold compared to unmodified AuNPs-BSH&PEG, indicating enhanced targeting due to cRGD's affinity for integrin receptor αvβ3. In a subcutaneous glioma mouse model, 6 hours post-intratumoral administration, the 10B concentration in tumors was 17.98 μg/g for AuNPs-BSH&PEG-cRGD, significantly higher than 0.45 μg/g for BSH. The tumor-to-blood (T/B) and tumor-to-normal tissue (T/N) ratios were also higher for AuNPs-BSH&PEG-cRGD, suggesting improved targeting and retention. This indicates that AuNPs-BSH&PEG-cRGD may enhance BNCT efficacy and minimize normal tissue toxicity. In summary, this study provides a novel strategy for BSH delivery and may broaden the design vision of BNCT nano-boron capture agents.
研究领域:
肿瘤学
·
纳米技术
·
放射治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Yan-Ping Li,Zi-Wen Pan,Yan-Jun Jiang,Ya-Yun Peng,Ting Cai,Hao Hong,Xiao-feng Wang
Nanoscale coordination polymer (NCP) is a class of hybrid materials formed by self-assembly of metal ions and organic ligands through coordination. The applications of NCP in biomedicine are quite extensive due to the diversity choice of metal ions and organic ligands. Here we designed Zr-P1 NCP based on Zr 4+ selected as metal ion nodes and tetrakis(4-carboxyphenyl) ethylene as bridging ligands. Zr-P1 NCP was modified with functionalized pyrene derived polyethylene glycol (Py-PAA-PEG-Mal) on the surface and further conjugated with cRGD for active targeting of integrin α v β 3 overexpressed in triple-negative breast cancer. Doxorubicin was loaded on Zr-P1 NCP with encapsulation efficiency up to 22% for the treatment of triple negative breast cancer. 89 Zr-P1 NCP can be used for in vivo tumor imaging due to the fluorescence properties resulting from the enhanced aggregation-induced Emission (AIE) behavior of P1 ligands and its positron emission tomography (PET) capability. Cellular evaluation indicated that the functionalized Zr-P1@PEG-RGD presented a good function for tumor cell targeting imaging and doxorubicin could be targeted to triple negative breast cancer when it was loaded onto Zr-P1@PEG-RGD, which corroborated with the in vivo results. In summary, 89 Zr-P1@PEG-RGD can serve as a biocompatible nanoplatform for fluorescence and PET image-guided cargo delivery. Statement of Significance Nanoscale coordination polymer (NCP) is a class of hybrid materials formed by self-assembly of metal ions and organic ligands through coordination. The diversity of available metals and ligand structures upon NCP synthesis plays an advantage in establishing multimodal imaging platforms. Here we designed 89 Zr-P1@PEG-RGD NCP based on Zr 4+ selected as metal ion nodes and tetrakis(4-carboxyphenyl) ethylene as bridging ligands. 89 Zr-P1@PEG-RGD nanomaterials have positron emission tomography (PET) capability due to the incorporation of zirconium-89, which can be used for in vivo tumor imaging with high sensitivity. The chemotherapeutic drug DOX was loaded on Zr-P1 NCP for the treatment of triple-negative breast cancer, and dual modality imaging can provide visual guidance for drug delivery.
研究领域:
生物医学工程
·
纳米技术
·
癌症研究
·
分子成像
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 41
·8152-8160
·
IF 4.543
Jie Zhang,Jie Wang,Tong Yan,Yanan Peng,Dajun Xu,Dawei Deng
Quantum dots (QDs) exhibit many unique optical properties, and show great promise as fluorescent markers in molecular, cellular and in vivo imaging. In this thematic issue, a major concern is their cytotoxicity. Among various Cd-free alternatives, InP-based QDs without highly toxic heavy metal elements have received the most attention. This article first focuses on the synthetic control of oil-soluble InP/ZnSe/ZnS QDs, exhibiting strong dual emissions, namely, visible excitonic emission and near-infrared (NIR) surface defect emission. Next, the organic-to-aqueous phase transfer of the dual emissive QDs was explored systematically. It was found that the dual emissions are relatively stable against the water transfer strategies used here; among them, aqueous dual emissive QDs obtained by wrapping oil-soluble QDs with a poly(acrylic acid)-octylamine (PAA-based) amphiphilic polymer (or modified with the cRGD peptide) exhibit enhanced NIR emission. Finally, using in vitro cell and in vivo small animal optical imaging techniques, the bioactivities of the cRGD-modified amphiphilic polymer-wrapped QDs were also investigated. The results confirm that single-wavelength excitation with strong dual emissions ranging from 550 to >1000 nm will endow the InP-based QDs with the capability for biomedical optical imaging across different spatial scales, as a promising alternative for Cd- and Pb-based QDs.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
光学成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2021
·Vol. 11
·期 2
·2101926
·
IF 9.933
Wenjie Feng,Wanrui Shi,Shuwei Liu,Huiwen Liu,Yi Liu,Pengfei Ge,Hao Zhang
Most of the antitumor chemotherapeutic drugs execute the therapeutic performance upon eliciting tumor cell apoptosis, which may cause chemoresistance of tumors. Design of novel drugs to eradicate apoptosis-resistant tumors via non-apoptotic cell death pathways is promising for improving the long-term chemotherapeutic efficacy. Herein, a Fe(III)-Shikonin metal-polyphenol-coordinated supramolecular nanomedicine for combined therapy of tumor via ferroptosis and necroptosis is designed. The construction of the nanomedicine based on the coordinated self-assembly between Fe 3+ and Shikonin not only overcomes the shortcomings of Shikonin including its low bioavailability and high toxicity toward normal tissues, but also integrates the theranostics functions of Fe ions. Under the exposure of the high concentration of glutathione (GSH) in tumor cells, the as-prepared nanomedicine will disassemble into Fe 2+ and Shikonin, followed by stimulating the tumor cell death through ferroptosis and necroptosis. In addition, benefiting from the stealth effect of polyethylene glycol (PEG) and the targeting ability of cyclo(Arg-Gly-Asp- d -Phe-Lys) (cRGD) to α v β 3 -integrin, NH 2 -PEG-cRGD-modified nanomedicine exhibits a GSH-responsive therapy toward 4T1 tumor in vivo and self-enhanced longitudinal relaxation (T 1 )-weighted imaging property. Since the self-assembly of natural Shikonin and human body-necessary Fe element is facile and feasible, the work may provide a promising supramolecular nanomedicine for next-generation chemotherapeutic applications.
研究领域:
纳米医学
·
肿瘤学
·
药物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Mengying Hou,Xuejie Wu,Ziyin Zhao,Qiurong Deng,Yongbing Chen,Lichen Yin
Neutrophils serve as a key contributor to the pathophysiology of myocardial ischemia reperfusion injury (MIRI), because the unregulated activation and infiltration of neutrophils lead to overwhelming inflammation in the myocardium to cause tissue damage. Herein, endothelial cell-targeting and reactive oxygen species (ROS)-ultrasensitive nanocomplexes (NCs) were developed to mediate efficient co-delivery of VCAM-1 siRNA (siVCAM-1) and dexamethasone (DXM), which cooperatively inhibited neutrophil recruitment by impeding neutrophil migration and adhesion. RPPT was first synthesized via crosslinking of PEI 600 with ditellurium followed by modification with PEG and the endothelial cell-targeting peptide cRGD. RPPT was allowed to envelope the DXM-loaded PLGA nanoparticles and condense the siVCAM-1. After systemic administration in rats experiencing MIRI, the cRGD-modified NCs efficiently targeted and entered the inflamed endothelial cells, wherein RPPT was sensitively degraded by over-produced ROS to trigger intracellular siVCAM-1 release and potentiate the VCAM-1 silencing efficiency. As a consequence of the complementary function of DXM and siVCAM-1, the NCs notably mitigated neutrophil infiltration into ischemic myocardium, provoking potent anti-inflammatory efficacy to reduce MIRI and recover cardiac function. The present study offers an effective approach for the controlled co-delivery of siRNA and drug cargoes, and it also highlights the importance of multi-dimensional manipulation of neutrophils in anti-inflammatory treatment. Statement of significance The unregulated activation and infiltration of neutrophils lead to overwhelming inflammation in the myocardium after myocardial ischemia reperfusion injury (MIRI). Here, endothelial cell-targeting and ROS-ultrasensitive nanocomplexes (NCs), comprised of PLGA NPs decorated with cRGD-poly(ethylene glycol) (PEG)-modified, ditellurium-crosslinked PEI (RPPT), were developed to mediate efficient co-delivery of VCAM-1 siRNA (siVCAM-1) and dexamethasone (DXM). DXM and siVCAM-1 with complementary functions inhibited both the migration and adhesion of neutrophils, efficiently interventing the neutrophil recruitment and interrupting the self-amplified inflammation cascade in the injured myocardium. The molecular design of RPPT renders an effective example for constructing polymeric materials with high ROS sensitivity, and it resolves the critical dilemma related to polycation-mediated siRNA delivery, such as siRNA encapsulation versus release, and transfection efficiency versus toxicity.
研究领域:
药学
·
纳米技术
·
心血管研究
·
分子生物学
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Qiuhui Hu,Yongzhao Su,Siying Ma,Peiying Wei,Chengbin He,Di Yang,Yue Qian,Youqing Shen,Xiaoxuan Zhou,Zhuxian Zhou,Hongjie Hu
Liver fibrosis is the critical stage in the development of chronic liver disease (CLD), from simple injury to irreversible cirrhosis. Timely detection and intervention of liver fibrosis are crucial for preventing CLD from progressing into a fatal condition. Herein, we developed iron oxide (Fe3O4) nanoparticles (IONPs) and ferulic acid (FA) coencapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), followed by surface modification with cRGD peptides (cRGD-PLGA/IOFA) for integrin-targeted clinical magnetic resonance imaging (MRI)-traceable treatment of liver fibrosis. The cRGD peptide linked on the surface of the PLGA/IOFA NPs could specifically bind to the overexpressed integrin αvβ3 on activated hepatic stellate cells (HSCs) in the fibrotic liver, enabling the high-sensitive clinical MR imaging (3 T) and precise staging of liver fibrosis. The FA encapsulated in cRGD-PLGA/IOFA showed excellent efficacy in reducing oxidative stress and inhibiting the activation of HSCs through the transforming growth factor-β (TGF-β)/Smad pathway. Notably, the IONPs encapsulated in cRGD-PLGA/IOFA NPs could alleviate liver fibrosis by regulating hepatic macrophages through the NF-κB pathway, lowering the proportion of Ly6Chigh/CD86+, and degrading collagen fibers. The FA and IONPs in the cRGD-PLGA/IOFA produced a synergistic enhancement effect on collagen degradation, which was more effective than the IONPs treatment alone. This study demonstrates that cRGD-PLGA/IOFA NPs could effectively relieve liver fibrosis by acting on macrophages and HSCs and provide a new strategy for the clinical MRI-traceable treatment of liver fibrosis.
研究领域:
纳米技术
·
生物医学工程
·
药理学
·
医学影像
·
肝病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Advances
·
2021
·Vol. 2
·期 9
·3020-3030
·
IF 0
Shengbei Qi,Chaoyong Liu,Meng Qin,Cheng Tao,Jie Liu,Yuan Le,Jiexin Wang,Jianjun Zhang,Yunfeng Lu
Photo-chemo combination therapy holds great promises for cancer treatment; thus developing efficient approaches for delivering photo-chemo combination reagents has long been pursued. Herein, an amphiphilic branched copolymer, four-arm poly(ethylene glycol)-poly(propylene sulfide)-cyclic(Arg-Gly-Asp-D-Phe-Lys) (PEG-PPS-cRGD), was synthesized to prepare targeted self-crosslinked polymer nanocapsules consisting of a disulfide bond and the αvβ3 integrin-targeting ligand cRGD. Furthermore, by coloading both indocyanine green (ICG) and doxorubicin (DOX) in PEG-PPS-cRGD nanocapsules, a high-performance photo-chemo combination therapeutic platform designated as DINCs was successfully developed. The dissolution rate investigations demonstrated that DINCs exhibited sensitive reduction-responsive drug release profiles during the incubation with glutathione (GSH), while the drug release rate could be further accelerated by NIR laser irradiation. The in vitro studies showed that DINCs had outstanding cellular uptake, photothermal effects and ROS generation under laser irradiation, which significantly enhanced cytotoxicity in the treatment of squamous cells (SCC-15). Moreover, the in vivo results showed that synergistic photo-chemo combination treatment by DINCs plus laser irradiation could completely eliminate the tumor of squamous cell carcinoma with favorable biological safety.
研究领域:
癌症治疗
·
聚合物科学
·
纳米技术
·
药物递送系统
·
生物医学工程
✓ 已验证
DOI
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Haitao Dou,Zixin Luo,Haodun Wang,Qicheng Duan,Zhuangzhuang Jiang,Huachao Chen,Ninghua Tan
Nanomaterial-based multi-modal synergistic therapies are emerging as highly promising strategies for the treatment of malignant tumors. Herein, a novel nanoplatform modified with the peptide of cyclo(Arg-Gly-Asp-D-Phe-Lys) (cRGD) was designed for synergistic treatment of hypoxic tumors by the combination of chemotherapy (CT)/photodynamic therapy (PDT)/photothermal therapy (PTT). Firstly, Mn@APDA nanoparticles were synthesized for PTT and oxygen (O 2 ) supply, consisting of an L-arginine-doped polydopamine (APDA) core and a manganese dioxide (MnO 2 ) shell. Subsequently, the liposome nanoplatform (cRGD-Lipo-MART), loaded with Mn@APDA (MA), chemotherapy drug of deoxybouvardin dodecyl ester (RA, “R” for short), and mitochondrial targeted photosensitizer of triphenylphosphine-grafted protoporphyrin IX (TPPP, “T” for short), was developed using a film dispersion method. Upon targeted delivery to tumors, the nanoplatform disintegrated in response to the acidic and hydrogen peroxide (H 2 O 2 )-rich tumor microenvironment (TME) and near-infrared (NIR) laser irradiation, thereby facilitating controlled drug release and O 2 supply to overcome hypoxia. The released RA could cause DNA damage and suppress the HIF-1α expression to sensitize PDT. Simultaneously, TPPP could generate singlet oxygen ( 1 O 2 ) and convert L-arginine (L-Arg) into nitric oxide (NO) for PDT, while APDA could induce hyperthermia for PTT. The combination of PDT and PTT resulted in significant mitochondrial dysfunction and lysosomal damage, ultimately leading to apoptosis. Furthermore, the chemotherapeutic effect of RA could be potentiated by the enhancement of cytoplasmic delivery caused by lysosomal disruption and the blocking of DNA damage repair pathway caused by mitochondrial dysfunction. Overall, cRGD-Lipo-MART, designed with a synergistic CT/PDT/PTT strategy, showed minimal systemic toxicity and could be used as an effective treatment for hypoxic tumors.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Zhuo Cheng,Chencheng Xue,Minghan Liu,Zhiming Cheng,Gan Tian,Menghuan Li,Rui Xue,Xuemei Yao,Yuan Zhang,Zhong Luo
Immunotherapy is an emerging antitumor modality with high specificity and persistence, but its application for resected tumor treatment is impeded by the low availability of tumor-specific antigens and strong immunosuppression in the wound margin. Here a nanoengineered hydrogel is developed for eliciting robust cooperative ferroptosis-immunotherapeutic effect on resected tumors. Specifically, β-cyclodextrin (β-CD) is first grafted onto oxidized sodium alginate (OSA) through Schiff base ligation, which could trap cRGD-modified redox-responsive Withaferin prodrugs (WA-cRGD) to obtain the hydrogel building blocks (Gel@WA-cRGD). Under Ca 2+ -mediated crosslinking, Gel@WA-cRGD rapidly forms physiologically stable hydrogels, of which the porous network is used to deliver programmed cell death ligand 1 antibodies (aPD-L1). After injection into the post-surgical wound cavity, the β-CD-entrapped WA-cRGD is detached by the local acidity and specifically internalized by residual tumor cells to trigger ferroptosis , thus releasing abundant damage-associated molecular patterns (DAMPs) and tumor-derived antigens for activating the antigen-presenting cell-mediated cross-presentation and downstream cytotoxic T cell (CTL)-mediated antitumor responses. Furthermore, aPD-L1 could block PD-1/PD-L1 interaction and enhance the effector function of CTLs to overcome tumor cell-mediated immunosuppression. This cooperative hydrogel-based antitumor strategy for ferroptosis-immunotherapy may serve as a generally-applicable approach for postoperative tumor management. Statement of significance To overcome the immunosuppressive microenvironment in resected solid tumors for enhanced patient survival, here we report a nanoengineered hydrogel incorporated supramolecular redox-activatable Withaferin prodrug and PD-L1 antibody, which could elicit robust cooperative ferroptosis-immunotherapeutic effect against residual tumor cells in the surgical bed to prevent tumor relapse, thus offering a generally-applicable approach for postoperative tumor management.
研究领域:
生物医学工程
·
癌症免疫治疗
·
药物科学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-20
·
IF 14.7
Guo Yichen,Li Yongjuan,Zhang Mengzhe,Ma Rong,Wang Yayun,Weng Xiao,Zhang Jinjie,Zhang Zhenzhong,Chen Xiaoyuan,Yang Weijing
The limited efficacy of cancer immunotherapy occurs due to the lack of spatiotemporal orchestration of adaptive immune response stimulation and immunosuppressive tumor microenvironment modulation. Herein, we report a nanoplatform fabricated using a pH-sensitive triblock copolymer synthesized by reversible addition-fragmentation chain transfer polymerization enabling in situ tumor vaccination and tumor-associated macrophages (TAMs) polarization. The nanocarrier itself can induce melanoma immunogenic cell death (ICD) via tertiary amines and thioethers concentrating on mitochondria to regulate metabolism in triggering endoplasmic reticulum stress and upregulating gasdermin D for pyroptosis as well as some features of ferroptosis and apoptosis. After the addition of ligand cyclic arginine-glycine-aspartic acid (cRGD) and mannose, the mixed nanocarrier with immune adjuvant resiquimod encapsulation can target B16F10 cells for in situ tumor vaccination and TAMs for M1 phenotype polarization. In vivo studies indicate that the mixed targeting nanoplatform elicits tumor ICD, dendritic cell maturation, TAM polarization, and cytotoxic T lymphocyte infiltration and inhibits melanoma volume growth. In combination with immune checkpoint blockade, the survival time of mice is markedly prolonged. This study provides a strategy for utilizing immunoactive materials in the innate and adaptive immune responses to augment cancer therapy.
研究领域:
癌症研究
·
纳米技术
·
免疫学
·
药学
·
生物医学工程
✓ 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）