INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2020
·
IF 4.845
Jianping Li,Man Li,Lifeng Tian,Yue Qiu,Qianwen Yu,Xuhui Wang,Rong Guo,Qin He
A facile approach was developed to synthesize an innovative hyaluronic acid-modified carbon dot-doxorubicin nanoparticles drug delivery platform. CD44 targeted HA-modified carbon dots (HA-CDs) were synthesized as carrier by one-step hydrothermal treatment within one hour with citric acid and branch-PEI as core carbon source. HA not only functioned as carbon dot component but also as hydrophilic group and targeting ligand of this system. The as-prepared HA-CDs were then loaded with doxorubicin (HA-CD@p-CBA-DOX) via an acid-cleavable bond, which released drug in a pH-responsive manner. In in vitro experiments, HA-CD@p-CBA-DOX displayed good hemocompatibility and serum stability, while exhibited high cytotoxicity on 4T1 cells. The confocal laser scanning microscopy and flow cytometry results demonstrated that DOX-loaded nanoparticles were internalized by 4T1 cells via HA-mediated CD44-targeting effect. The enhanced in vivo tumor accumulation of HA-CD@p-CBA-DOX was testified by live imaging. Compared with free DOX, superior in vivo anti-tumor efficacy of HA-CD@p-CBA-DOX was observed in both heterotopic and orthotopic 4T1 cell tumor models. Furthermore, blood hematology and blood biochemistry analysis demonstrated that HA-CD@p-CBA-DOX did not induce noticeable toxicity, which further confirmed the good biocompatibility of HA-CD@p-CBA-DOX. The formulated HA-CD@p-CBA-DOX provides an alternative strategy for targeted breast cancer therapy.
研究领域:
药剂学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2021
·
IF 9.381
Qi Chen,Xiaorong Li,Yuan Xie,Weicheng Hu,Zhipeng Cheng,Hui Zhong,Hongjun Zhu
Herein, we demonstrate a novel UV-induced decomposable nanocapsule of natural polysaccharide (HA-azo/PDADMAC). The nanocapsules are fabricated based on layer-by-layer co -assembly of anionic azobenzene functionalized hyaluronic acid (HA-azo) and cationic poly diallyl dimethylammonium chloride (PDADMAC). When the nanocapsules are exposed to 365 nm light, ultraviolet photons can trigger the photo-isomerization of azobenzene groups in the framework. The nanocapsules could decompose from large-sized nanocapsules to small fragments. Due to their optimized original size (~180 nm), the nanocapsules can effectively avoid biological barriers, provide a long blood circulation and achieve high tumor accumulation. It can fast eliminate nanocapsules from tumor and release the loaded drugs for chemotherapy after UV-induced dissociation. Besides, HA is an endogenous polysaccharide that shows intrinsic targetability to CD44 receptors on surface of cancer cells. The intracellular experiment shows that the HA-azo/PDADMAC nanocapsules with CD44 targeting ability and UV-controlled intracellular drug release are promising for cancer chemotherapy.
研究领域:
药学
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肿瘤学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2019
·
IF 3.829
Mengna Liu,Bingjie Wang,Chunjing Guo,Xiaoya Hou,Ziting Cheng,Daquan Chen
In this study, novel multifunctional folic acid, biotin, and CD44 receptors targeted and pH-sensitive “nano-actiniaes” were fabricated with icariin (ICA) and curcumin (Cur) as loaded model drugs for breast cancer therapy. The newly synthesized polymer oligomeric hyaluronic acid-hydrazone bond-folic acid-biotin (Bio-oHA-Hyd-FA) was characterized by 1H NMR spectrogram (proton nuclear magnetic resonance). The obtained drug carrier Bio-oHA-Hyd-FA self-assembled into nanomicelles, named as “nano-actiniaes”, in aqueous media with hydrodynamic diameter of 162.7 ± 5 nm. The size, surface zeta potential, and morphology of the “nano-actiniaes” were observed via TEM. The in vitro release experiment indicated that much more encapsulated icariin (ICA) and curcumin (Cur) were released from the Bio-oHA-Hyd-FA micelles (nano-actiniaes) in the acidic environment. Additionally, the cytotoxicity research demonstrated that the Bio-oHA-Hyd-FA carrier material was completely nontoxic, and the ICA&Cur “nano-actiniaes” had greater cytotoxicity compared with other control groups. In addition, the “nano-actiniaes” were found to significantly inhibit cancer cell invasion by Transwell assay. Moreover, in vivo evaluation of anti-tumor effect illustrated that the ICA and Cur “nano-actiniaes” possessed inhibitory effect on tumors. Consequently, the multi-targeted pH-sensitive “nano-actiniaes” can realize significant tumor targeting and effectively inhibit tumor growth.
研究领域:
药剂学
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肿瘤学
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生物材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-14
·
IF 10.6
Luo Wenqi,Li Yueying,Zhao Jianhui,Niu Renrui,Xiang Chunyu,Zhang Mingyu,Xiao Chunsheng,Liu Wanguo,Gu Rui
Background Therapeutic strategies based on scavenging reactive oxygen species (ROS) and suppressing inflammatory cascades are effective in improving functional recovery after spinal cord injury (SCI). However, the lack of targeting nanoparticles (NPs) with powerful antioxidant and anti-inflammatory properties hampers the clinical translation of these strategies. Here, CD44-targeting hyaluronic acid-selenium (HA-Se) NPs were designed and prepared for scavenging ROS and suppressing inflammatory responses in the injured spinal cord, enhancing functional recovery.Results The HA-Se NPs were easily prepared through direct reduction of seleninic acid in the presence of HA. The obtained HA-Se NPs exhibited a remarkable capacity to eliminate free radicals and CD44 receptor-facilitated internalization by astrocytes. Moreover, the HA-Se NPs effectively mitigated the secretion of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6) by microglia cells (BV2) upon lipopolysaccharide-induced inflammation. In vivo experiments confirmed that HA-Se NPs could effectively accumulate within the lesion site through CD44 targeting. As a result, HA-Se NPs demonstrated superior protection of axons and neurons within the injury site, leading to enhanced functional recovery in a rat model of SCI.Conclusion sThese results highlight the potential of CD44-targeting HA-Se NPs for SCI treatment.
研究领域:
神经科学
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纳米医学
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药理学
✓ 已验证
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2016
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IF 3.902
Jing Zhang,Yujie Sun,Baocheng Tian,Keke Li,Lele Wang,Yan Liang,Jingtian Han
In this paper, a CD44-targeted and redox-responsive drug delivery system based on mesoporous silica nanoparticles (MSNs) was synthesized by conjugating tumor-shedable hyaluronic acid (HA) on the surface of MSNs via disulfide bonds. Doxorubicin hydrochloride (DOX·HCl) was physically encapsulated into HA modified MSNs (MSNs/SS/HA@DOX) as a model drug. MSNs/SS/HA@DOX (40 nm) had a high drug loading (14.1%) and redox-responsive drug release property. The cellular uptake behaviors of MSNs/SS/HA@DOX by HeLa and LO2 cells were evaluated by confocal laser scanning microscopy (CLSM) and flow cytometry (FCM). MSNs/SS/HA@DOX exhibited higher cellular uptake efficacy via CD44-mediated endocytosis by HeLa cells (CD44 over-expressed cells) than by LO2 cells (CD44 deficient cells). The in vitro cytotoxicity assay demonstrated that MSNs/SS/HA@DOX exhibited higher cytotoxicity to HeLa cells than to LO2 cells. These results indicated that MSNs/SS/HA@DOX might be promising as a multifunctional drug delivery system to improve the anti-tumor efficacy of chemotherapeutic drugs.
研究领域:
药剂学
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肿瘤学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Yao-Hui Zhang,Wen-Xiu Qiu,Mingkang Zhang,Lu Zhang,Xian-Zheng Zhang
Here, a tumor-targeted MnO2 motor nanosystem (designed as MG/HA) was constructed by the assembly of glucose oxidase (GOD), manganese dioxide (MnO2), and glycoprotein CD44-targeting polymer hyaluronic acid (HA) to elevate cancer-starving therapy efficacy in solid tumor. Upon the specific uptake of MG/HA by CD44 overexpressed cancer cells, GOD catalyzed the oxidation of glucose into gluconic acid and hydrogen peroxide (H2O2) accompanying the consumption of oxygen (O2). Meanwhile, MnO2 would react with H2O2 and acid to generate O2, which is in turn supplied to the glucose-depletion process, running like a loop. As a result, MnO2 is displayed as a motor to promote the rate of glucose depletion that contributed to the starving therapy. In contrast to G/HA, MG/HA could not only achieve effective glucose consumption to depress cancer progression, but also alleviate hypoxia and reduce the expression of Glut1 to inhibit the metabolism for further restraining the tumor aggressiveness and metastasis. The concept of MnO2 motor shows a promising prospect to overcome the restriction of the starving therapy.
研究领域:
肿瘤学
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生物医学工程
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Xianshuo Zhang,Peipei Wang,Xinsheng Wang,Yaoyu Xu,Taolin Cheng,Chengjie Zhang,Jiaying Ding,Yunfeng Shi,Wei Ma,Cui-Yun Yu,Hua Wei
Hyaluronic acid (HA)-based tumor microenvironment-responsive nanocontainers are attractive candidates for anticancer drug delivery due to HA's excellent biocompatibility , biodegradability, and CD44-targeting properties. Nevertheless, the consecutive synthesis of stabilized, stealthy, responsive HA-based multicomponent nanomedicines generally requires multi-step preparation and purification procedures, leading to batch-to-batch variation and scale-up difficulties. To develop a facile yet robust strategy for promoted translations, a silica monomer containing a cross-linkable diethoxysilyl unit was prepared to enable in situ crosslinking without any additives. Further combined with the host-guest inclusion complexation between β -cyclodextrin-grafted HA (HA-CD) and ferrocene-functionalized polymers, ferrocene-terminated poly(oligo(ethylene glycol) methyl ether methacrylate (Fc-POEGMA) and Fc-terminated poly( ε -caprolactone)- b -poly(3-(diethoxymethylsilyl)propyl(2-(methacryloyloxy)ethyl) carbamate) (Fc-PCL- b -PDESPMA), a reactive oxygen species (ROS)-sensitive supramolecular polymer construct, Fc-POEGMA/Fc-PCL- b -PDESPMA@HA-CD was readily fabricated to integrate stealthy POEGMA, tumor active targeting HA, and an in situ cross-linkable PDESPMA sequence. Supramolecular amphiphilic copolymers with two different POEGMA contents of 25 wt% ( P1 ) and 20 wt% ( P2 ) were prepared via a simple physical mixing process, affording two core-crosslinked (CCL) micelles via an in situ sol-gel process of ethoxysilyl groups. The P1 -based CCL micelles show not only desired colloidal stability against high dilution, but also an intracellular ROS-mimicking environment-induced particulate aggregation that is beneficial for promoted intracellular release of the loaded cargoes. Most importantly, P1 -based nanomedicines exhibited greater cytotoxicity in CD44 receptor-positive HeLa cells than that in CD44 receptor-negative MCF-7 cells. Overall, this work developed HA-based nanomedicines with sufficient extracellular colloidal stability and efficient intracellular destabilization properties for enhanced anticancer drug delivery via smart integration of in situ crosslinking and supramolecular complexation.
研究领域:
纳米医学
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癌症研究
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药物递送系统
·
材料科学
✓ 已验证
DOI
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yiwen Chen,Zhen Qin,Yujia Wang,Baoxin Gu,Jing Wang,Yunfei Zheng,Yuting Niu,Lingfei Jia
Cancer stem cells (CSCs) play critical roles in tumor growth, metastasis, and chemoresistance. Although several small-molecule inhibitors designed to inhibit CSCs have been investigated in clinical trials, their inadequate tumor targeting and potential off-target side effects have led to poor outcomes. A CD44-targeted virus-mimicking nanomedicine encapsulating the BMI1 inhibitor PTC209 (PTC209@VNP-HA) was designed to treat head and neck squamous cell carcinoma (HNSCC). We used a dendritic mesoporous silica nanoparticle (MSN) as the core for virus-mimicking nanoparticle (VNP) formation after adding shell particles to the MSN surface. The VNP surface was then modified with hyaluronic acid (HA), and PTC209 was adsorbed by mesopores to form PTC209@VNP-HA. In this system, HA is used to target CD44 + CSCs. The rough surface of VNP-HA provided better drug delivery efficiency than smooth nanoparticles modified with HA. VNP-HA enhanced the cancer inhibitory effect of PTC209 12-fold compared to the administration of free PTC209, leading to significantly higher bioavailability of PTC209. Both in vitro and in vivo assays showed that PTC209@VNP-HA inhibited cancer stemness, proliferation, and metastasis in HNSCC. Mechanistically, this inhibitory effect is closely associated with DNA damage/apoptosis signaling. Using a series of preclinical models in murine systems, we confirmed that PTC209@VNP-HA eliminated BMI1 + CSCs, and greatly inhibited the proliferation and metastasis of HNSCC when combined with cisplatin.This study investigated PTC209@VNP-HA as a novel and potentially transformative HNSCC treatment option that eliminates CSCs, prevents metastasis, and overcomes cisplatin resistance.
研究领域:
肿瘤学
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纳米医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2020
·Vol. 10
·期 3
·2001029
·
IF 7.367
Shuo Huang,Linlin Zhang,Miaomiao Xu,Chao Li,Hongliang Fu,Jie Huang,Xin Jin,Sheng Liang,Hui Wang
New radionuclide-labeled targeting nanocarrier systems have generated new opportunities for tumor treatment and imaging. Nevertheless, such therapeutic strategy is clinically unfeasible on anaplastic thyroid carcinoma (ATC) patients, because of lacking suitable targets and resistance to radiation. In order to figure out a potential treatment, immuno-histochemical staining is performed in human ATC tissue species and high expression of cluster determinant 44 (CD44) is found. Therefore, a CD44-targeted delivery system is designed and constructed by self-assembly of tyrosine (Tyr)–hyaluronic acid (HA)–polyethyleneimine (PEI), which can radiolabel 131/125 I and load a p53 mutant restoring regent, Prima-1. The 125 I-labeled nanocomposites display an impressive tumor imaging as well as a long radiation treatment cycle. The 131 I-labeled nanoparticles show remarkable anti ATC-tumor effects in vitro and in vivo, due to radiosensitization of Prima-1 by reactivation of the p53 mutants.
研究领域:
纳米技术
·
肿瘤学
·
放射学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
·
2023
·Vol. 42
·期 1
·1-13
·
IF 11.3
Liu Ruolan,Li Qiong,Qin Siyuan,Qiao Ling,Yang Mei,Liu Shanshan,Nice Edouard C.,Zhang Wei,Huang Canhua,Zheng Shaojiang,Gao Wei
Background Lung cancer is one of the most frequent causes of cancer-related deaths worldwide. Drug repurposing and nano-drug delivery systems are attracting considerable attention for improving anti-cancer therapy. Sertaconazole (STZ), an antifungal agent, has been reported to exhibit cytotoxicity against both normal and tumor cells, and its medical use is limited by its poor solubility. In order to overcome such shortcomings, we prepared a drug-repurposed nanoplatform to enhance the anti-tumor efficiency. Methods Nanoplatform was prepared by thin film dispersion. Drug release studies and uptake studies were measured in vitro. Subsequently, we verified the tumor inhibition mechanisms of HTS NPs through apoptosis assay, immunoblotting and reactive oxygen species (ROS) detection analyses. Antitumor activity was evaluated on an established xenograft lung cancer model in vivo. Results Our nanoplatform improved the solubility of sertaconazole and increased its accumulation in tumor cells. Mechanistically, HTS NPs was dependent on ROS-mediated apoptosis and pro-apoptotic autophagy to achieve their excellent anti-tumor effects. Furthermore, HTS NPs also showed strong inhibitory ability in nude mouse xenograft models without significant side effects. Conclusions Our results suggest that sertaconazole-repurposed nanoplatform provides an effective strategy for lung cancer treatment.
研究领域:
药理学
·
肿瘤学
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纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Fengzhi Qiao,Ya Luo,Peng Lei,Shaolei Wang,Zhi Duan,Hongchang Cui,Tongjie Liu,Huaxi Yi,Cristabelle De Souza,Guanhua Xuan,Xiangzhao Mao,Zhao Ma,Lanwei Zhang,Kai Lin
Probiotics play a crucial role in regulating intestinal immune homeostasis and supporting gut health; however, oral administration faces challenges such as nonspecific distribution and low efficacy. To achieve precise and efficient delivery, in this study, a targeted delivery system embedded probiotics to the colonic inflammatory site CD44 was constructed by covalently linking hyaluronic acid (HA) to cysteine-modified chitosan (CCH) using microfluidic technology. Two probiotic strains, Bifidobacterium bifidum FL-276.1 and Clostridium butyricum ATCC 19398, were encapsulated within the modified chitosan matrix to form probiotics@CCH microspheres (MSs), with an average diameter of approximately 276 μm. Based on the receptor–ligand binding mechanism of HA and CD44, combined with the intestinal mucosal adhesion properties conferred by cysteine-modified chitosan, the probiotics@CCH MSs exhibited a high capture rate for inflammatory Caco-2 cells and demonstrated prolonged retention and targeted localization in a DSS-induced colitis mouse model. Furthermore, probiotics@CCH MSs contributed to maintaining intestinal homeostasis by modulating gut microbiota composition, enhancing short-chain fatty acid production, and supporting the intestinal barrier integrity. The microfluidic-based delivery system facilitates the precise localization of probiotics within the intestine, providing a theoretical basis for enhancing probiotic applications in gut health management.
研究领域:
生物医学工程
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药学
·
胃肠病学
·
微生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2020
·
IF 8.352
Xueqin Wang,Tiandi Xiong,Miao Cui,Xinglei Guan,Jiacheng Yuan,Zichao Wang,Ruifang Li,Huiru Zhang,Shaofeng Duan,Fang Wei
Catalytic nanozyme-based tumor therapy is currently considered as a promising strategy in anti-tumor treatment, but it also has some disadvantages such as systemic toxicity, off-target, and non-specificity, leading to lowered therapeutic precision and efficacy in clinical curability. To overcome these limitations, herein we report a distinct strategy of nanocatalytic tumor precision therapy via tumor cell-specific CD44 targeted nanozyme-catalyzed cascade reactions. Briefly, the composite nanozyme CD44 MMSN/AuNPs were assembled with two self-activable nanocatalysts including the inner core peroxidase-mimic Fe 3 O 4 magnetic nanoparticles (MNPs), and the outer glucose oxidase-mimic AuNPs situated within large aperture mesoporous silicon (MMSN/AuNPs), and then functionalized with cell ligand hyaluronic acid (HA), which can specifically target transmembrane CD44 receptor of HepG2 tumor cells. In terms of catalysis, we found the coupled AuNPs effectively catalyzed glucose to produce H 2 O 2 , which was inversely catalyzed by Fe 3 O 4 NPs and AuNPs to produce more hydroxyl radicals (•OH) in tumor microenvironment (TME). That is, this composite nanozyme performed self-activable reactive oxygen species (ROS)-mediated cascade reactions, and thereby resulted in significantly specific growth inhibition of hepatocellular carcinoma HepG2 cells. The present results also showed that the composite nanozyme CD44 MMSN/AuNPs could specifically induce a greater number of HepG2 cell apoptosis and death. More importantly, we elucidated the mechanism of the composite nanozyme CD44 MMSN/AuNPs via inducing HepG2 cell apoptosis and death from subcellular level. Therefore, this study represents an insightful paradigm for achieving nanocatalytic tumor precision therapy through rationally designing tumor cell-targeting inorganic nanozyme with self-activable cascade reactions.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
✓ 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）