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EUROPEAN POLYMER JOURNAL · 2022 · IF 5.546

Dual responsive molecularly imprinted polymers based on UiO-66-DOX for selective targeting tumor cells and controlled drug release

Shuang Han,Yuzhuo Song,Shiwei Liu,Le Zhao,Ruonan Sun

The preparation of synthetic drug delivery systems free of antibody modifications that can effectively recognize tumor sites and control drug delivery is essential for cancer therapy. In this study, UiO-66 metal–organic framework (MOF) modified with amino and phenylboronic acid groups was used as substrate to load the anti-cancer drug doxorubicin (DOX). Then a molecularly imprinted polymer (UiO-66-DOX@MIP) with sialic acid (SA) as the template molecule was further prepared on the surface of the synthesized nanoparticles using surface molecular imprinting technique (MIT). This polymer combines the excellent properties of UiO-66 and molecularly imprinted polymer (MIP). It was simple to prepare, economical and easy to obtain, and had a regular morphology. UiO-66-DOX@MIP containing molecularly imprinted binding sites that match the template molecule SA, could specifically recognize target tumor cells. The imprinted layer prevented drug leakage in normal body fluids while degrading and drug release under tumor microenvironment, with pH and glutathione (GSH) dual-responsive drug release properties. The UiO-66-DOX@MIP showed excellent biocompatibility and great cellular uptake efficiency to cancer cells without influence of interfering substances.

研究领域: 生物材料学 · 药物递送系统 · 癌症治疗
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International Journal of Nanomedicine · 2023 · IF 8

In vitro and in vivo Evaluation of Folic Acid Modified DOX-Loaded 32P-nHA Nanoparticles in Prostate Cancer Therapy

Hao Deng,Yumei Wang,Yue Zhou,Dongliang Zhai,Jie Chen,Shilei Hao,Xiaoliang Chen

Background Prostate cancer (PCa) ranks second in the incidence of all malignancies in male worldwide. The presence of multi-organ metastases and tumor heterogeneity often leads to unsatisfactory outcomes of conventional radiotherapy treatments. This study aimed to develop a novel folate-targeted nanohydroxyapatite (nHA) coupling to deliver adriamycin (Doxorubicin, DOX), 32P, and 99mTc simultaneously for the diagnosis and treatment of prostate-specific membrane antigen (PSMA) positive prostate cancer.Methods The spherical nHA was prepared by the biomimetic method and characterized. Folic acid (FA) was coupled to nHA with polyethylene glycol (PEG), and the grafting ratio of PEG-nHA and FA-PEG-nHA was determined by the thermogravimetric analysis (TGA) method. In addition, 32P, 99mTc, and DOX were loaded on nHA by physisorption. And the labeling rate and stability of radionuclides were measured by a γ-counter. The loading and release of DOX at different pH were determined by the dialysis method. Targeting of FA-PEG-nHA loaded with 99mTc was verified by in vivo SPECT imaging. In vitro anti-tumor effect of 32P/DOX-FA-PEG-nHA was assessed with apoptosis assay. The safety of the nano-drugs was verified by histopathological analysis.Results The SEM images showed that the synthesized nHA was spherical with uniform particle size (average diameter of about 100nm). The grafting ratio is about 10% for PEG and about 20% for FA. The drug loading and the delayed release of DOX at different pH confirmed its long-term therapeutic ability. The labeling of 32P and 99mTc was stable and the labeling rate was great. SPECT showed that FA-PEG-nHA showed well in vivo tumor targeting and less damage to normal tissues.Conclusion FA-targeted nHA loaded with 32P, 99mTc, and DOX may be a new diagnostic and therapeutic strategy for targeting PSMA-positive prostate cancer tumors, which may achieve better therapeutic results while circumventing the severe toxic side effects of conventional chemotherapeutic agents.

CAS / MDL: 538-75-0 6066-82-6
研究领域: 肿瘤学 · 药剂学 · 核医学
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BIOMATERIALS · 2013 · IF 7.604

Ultra-small BaGdF5-based upconversion nanoparticles as drug carriers and multimodal imaging probes

Dongmei Yang,Yunlu Dai,Jianhua Liu,Ying Zhou,Yinyin Chen,Chunxia Li,Ping'an Ma,Jun Lin

A new type of drug-delivery system (DDS) was constructed, in which the anti-cancer drug doxorubicin (DOX) was conjugated to the ultra-small sized (sub-10 nm) BaGdF 5 :Yb 3+ /Tm 3+ based upconversion nanoparticles (UCNPs). This multifunctional DDS simultaneously possesses drug delivery and optical/magnetic/X-ray computed tomography imaging capabilities. The DOX can be selectively released by cleavage of hydrazone bonds in acidic environment, which shows a pH-triggered drug release behavior. The MTT assay shows these DOX-conjugated UCNPs exhibit obvious cytotoxic effect on HeLa cells . Moreover, to improve the upconversion luminescence intensity, core–shell structured UCNPs were constructed. The in vitro upconversion luminescence images of these UCNPs uptaken by HeLa cells show bright emission with high contrast. In addition, these UCNPs were further explored for T 1 -weighted magnetic resonance (MR) and X-ray computed tomography (CT) imaging in vitro . Long-term in vivo toxicity studies indicated that mice intravenously injected with 10 mg/kg of UCNPs survived for 40 days without any apparent adverse effects to their health. The results indicate that this multifunctional drug-delivery system with optimized size, excellent optical/MR/CT trimodal imaging capabilities, and pH-triggered drug release property is expected to be a promising platform for simultaneous cancer therapy and bioimaging .

研究领域: 纳米医学 · 生物医学工程 · 肿瘤学
✓ 已验证 DOI PubMed 高影响因子
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POLYMER · 2011 · IF 3.829

Sheddable micelles based on disulfide-linked hybrid PEG-polypeptide copolymer for intracellular drug delivery

Tian-Bin Ren,Wen-Juan Xia,Hai-Qing Dong,Yong-Yong Li

A novel reduction-sensitive sheddable micelle based on disulfide-linked hybrid PEG-polypeptide mPEG-SS-Pleu was demonstrated for intracellular drug delivery . These micelles are composed of an mPEG shell and polypeptide core, characterized by FT-IR, 1 H NMR, fluorescence techniques, TEM , and DLS . Interestingly, they would undergo a fast sheddable process when encounter the reduction sensitive condition, indicated by the aggregation phenomena in the presence of DTT, a reduction agent, which could cleave the disulfide bond between the micellar core and shell and consequently leading to the aggregation of hydrophobic core. Cytotoxicity study revealed that copolymers in this system have good biocompatibility and their self-assembled micelles showed a high drug loading efficiency for DOX , a hydrophobic drug model, and released DOX quantitatively in response to the intracellular level of reducing potential. Cellular uptake experiments demonstrated that the fluorescently labeled micelles could be successfully internalized into human liver carcinoma HepG2 cells, evidenced by confocal laser scanning microscopy . Above results indicate that the copolymers may have great potential in drug delivery to achieve improved cancer therapy.

研究领域: 药剂学 · 生物材料学 · 肿瘤学
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Materials Science & Engineering C-Materials for Biological Applications · 2016 · IF 3.42

A pH-sensitive hyaluronic acid prodrug modified with lactoferrin for glioma dual-targeted treatment

Yatao Yin,Chaoping Fu,Mei Li,Xiangpen Li,Mengying Wang,Lei He,Li-Ming Zhang,Ying Peng

Gliomas are the most common and lethal type of primary malignant brain tumor. But the existence of blood brain barrier (BBB) and blood-tumor barrier (BTB) hinder drug from reaching the tumor site. To address this problem, we developed a novel prodrug (Lf-HA-DOX) by conjugating hyaluronic acid with doxorubicin (HA-DOX) by an acid-labile hydrazone linkage, which is released in an acidic environment and accumulates in tumor tissues. Lactoferrin (Lf) was coupled for transporting across the BBB. In vitro, the release of DOX from Lf-HA-DOX was pH-dependent. At lower pH (5.0 and 6.0), the release of DOX was much quicker than that at pH   7.4. In the cellular uptake studies, flow cytometry analyses and confocal laser scanning microscopy results showed significantly enhanced cellular uptake of Lf-HA-DOX and HA-DOX in C6 cells compared to DOX. In BALB/C mice bearing C6 glioma, enhanced accumulation of Lf-HA-DOX in the glioma was observed by real time fluorescence image. Correspondingly, glioma-bearing mice treated with Lf-HA-DOX displayed the longest median survival time, which was 2-fold longer than that of saline group. In conclusion, Lf-HA-DOX was able to significantly increase drug delivery to the glioma, which might provide a promising strategy for antiglioma therapy.

研究领域: 药理学 · 神经科学 · 肿瘤学 · 药物递送系统
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2018 · IF 3.997

A new drug carrier with oxygen generation function for modulating tumor hypoxia microenvironment in cancer chemotherapy

Zhe Zhang,Na Niu,Xi Gao,Fuqin Han,Zhijun Chen,Shujun Li,Jian Li

Hypoxia is the main characteristic of tumor microenvironment, and the one of the key factors that cause the drug resistance of cancer cells for chemotherapy. Anticancer drug such as DOX cannot react with sufficient oxygen to produce reactive oxygen species (ROS) in hypoxic environment, which affects the therapeutic efficiency of the drug. In this work, we constructed a multi-functional nano-carrier (named as FeSiAuO) containing Fe 3 O 4 , mesoporous SiO 2 and Au 2 O 3 with magnetic, large surface ratio and light induced oxygen production properties. The Au 2 O 3 may decompose into oxygen (O 2 ) and Au under the light irradiation to improve the oxygen concentration of the microenvironment of cancer cells, which increases the sensitivity of cancer cells to drug (DOX), reduces the drug resistance, and effectively exerts the anticancer effect of DOX. Meanwhile, the release of the as-loaded DOX molecule from the porous of SiO 2 will be also promoted under light irradiation in diverse pH conditions. With the helping of the magnet effect of the Fe 3 O 4 , the DOX can be also targeted delivered to the tumor site under the magnetic field. All of above results were thoroughly examined by the cell and small animal assays, which demonstrate that the FeSiAuO can be served as the multifunctional drug nano-carrier to achieve the targeted high-efficient cancer therapy.

研究领域: 肿瘤学 · 药剂学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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International Journal of Nanomedicine · 2024 · IF 6.6

Hybrid Liposome-MSN System with Co-Delivering Potential Effective Against Multidrug-Resistant Tumor Targets in Mice Model

Yanan Yang,Shuoye Yang,Beibei Zhang,Jinpeng Wang,Di Meng,Lan Cui,Lu Zhang

Introduction RNA interference (RNAi) stands as a widely employed gene interference technology, with small interfering RNA (siRNA) emerging as a promising tool for cancer treatment. However, the inherent limitations of siRNA, such as easy degradation and low bioavailability, hamper its efficacy in cancer therapy. To address these challenges, this study focused on the development of a nanocarrier system (HLM-N@DOX/R) capable of delivering both siRNA and doxorubicin for the treatment of breast cancer.Methods The study involved a comprehensive investigation into various characteristics of the nanocarrier, including shape, diameter, Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), encapsulation efficiency, and drug loading. Subsequently, in vitro and in vivo studies were conducted on cytotoxicity, cellular uptake, cellular immunofluorescence, lysosome escape, and mouse tumor models to evaluate the efficacy of the nanocarrier in reversing tumor multidrug resistance and anti-tumor effects.Results The results showed that HLM-N@DOX/R had a high encapsulation efficiency and drug loading capacity, and exhibited pH/redox dual responsive drug release characteristics. In vitro and in vivo studies showed that HLM-N@DOX/R inhibited the expression of P-gp by 80%, inhibited MDR tumor growth by 71% and eliminated P protein mediated multidrug resistance.Conclusion In summary, HLM-N holds tremendous potential as an effective and targeted co-delivery system for DOX and P-gp siRNA, offering a promising strategy for overcoming MDR in breast cancer.

研究领域: 癌症治疗 · 纳米技术 · 药学 · 分子生物学
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ACS Applied Materials & Interfaces · 2018 · IF 8.097

pH-Responsive Magnetic Mesoporous Silica-Based Nanoplatform for Synergistic Photodynamic Therapy/Chemotherapy

Xiang-long Tang,Feng Jing,Ben-lan Lin,Sheng Cui,Ru-tong Yu,Xiao-dong Shen,Ting-wei Wang

By overcoming drug resistance and subsequently enhancing the treatment, the combination therapy of photodynamic therapy (PDT) and chemotherapy has promising potential for cancer treatment. However, the major challenge is how to establish an advanced nanoplatform that can be efficiently guided to tumor sites and can then stably release both chemotherapy drugs and a photosensitizer simultaneously and precisely. In this study, which considered the possibility and targeting efficiency of a magnetic targeting strategy, a novel Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was successfully built; this platform could be employed as an efficient synergistic antitumor nanoplatform with magnetic guidance for highly specific targeting and retention. Doxorubicin (DOX) molecules were loaded into mesoporous silica with high loading capability, and the mesoporous channels were blocked by a polydopamine coating. Human serum albumin (HSA) was conjugated to the outer surface to increase the biocompatibility and blood circulation time, as well as to provide a vehicle for loading photosensitizer chlorin e6 (Ce6). The sustained release of DOX under acidic conditions and the PDT induced by red light exerted a synergistic inhibitory effect on glioma cells. Our experiments demonstrated that the pH-responsive Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was guided to the tumor region by magnetic targeting and that the nanoplatform suppressed glioma tumor growth efficiently, implying that the system is a highly promising photodynamic therapy/chemotherapy combination nanoplatform with synergistic effects for cancer treatment.

研究领域: 纳米技术 · 癌症研究 · 生物医学工程 · 药学
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Nanomaterials · 2019 ·Vol. 9 ·期 5 ·797 · IF 4.034

Facile and Controllable Fabrication of Protein-Only Nanoparticles through Photo-Induced Crosslinking of Albumin and Their Application as DOX Carriers

Xiangyu Long,Jun Ren,Chao Zhang,Fangling Ji,Lingyun Jia

Protein-based nanoparticles, as an alternative to conventional polymer-based nanoparticles, offer great advantages in biomedical applications owing to their functional and biocompatible characteristics. However, the route of fabrication towards protein-based nanoparticles faces substantial challenges, including limitations in size control and unavoidable usage of toxic crosslinkers or organic solvents, which may raise safety concerns related to products and their degradation components. In the present study, a photo-induced crosslinking approach was developed to prepare stable, size-controlled protein-only nanoparticles. The facile one-step reaction irradiated by visible light enables the formation of monodispersed bovine serum albumin nanoparticles (BSA NPs) within several minutes through a tyrosine photo-redox reaction, requiring no cross-linking agents. The size of the BSA NPs could be precisely manipulated (from 20 to 100 nm) by controlling the duration time of illumination. The resultant BSA NPs exhibited spherical morphology, and the α-helix structure in BSA was preserved. Further study demonstrated that the 35 nm doxorubicin (DOX)-loaded BSA NPs achieved a drug loading content of 6.3%, encapsulation efficiency of 70.7%, and a controlled release profile with responsivity to both pH and reducing conditions. Importantly, the in vitro drug delivery experiment demonstrated efficient cellular internalizations of the DOX-loaded BSA NPs and inhibitory activities on MCF-7 and HeLa cells. This method shows the promise of being a platform for the green synthesis of protein-only nanoparticles for biomedical applications.Keywords:protein-only nanoparticles;drug delivery;BSA;photo-induced crosslinking;biomedical application

研究领域: 纳米技术 · 生物医学工程 · 药学
✓ 已验证 DOI PubMed 高影响因子
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Small · 2026 · IF 12.1

Harnessing Boron-Mediated Ti Valence Cycling in TiB2-PEG-DOX: A Multimodal CDT/PTT/CT Platform for Colorectal Cancer Therapy

Yueguang Fang,Chenxi Li,Xinqi Li,Lanling Xiu,Dingwen Xiao,Miao Wang,Lin Sun,Junwei Ye

Titanium-based materials hold great biomedical potential owing to excellent biocompatibility. But titanium diboride (TiB 2 ), an emerging metal boride, is rarely explored for antitumor use, and developing multifunctional TiB 2 -based nanoplatforms with enhanced catalytic activity is urgently needed. Herein, we constructed a nanoplatform (TiB 2 -PEG-DOX) by modifying TiB 2 nanosheets (TiB 2 NSs) with amino polyethylene glycol (NH 2 -PEG-NH 2 ) and loading doxorubicin (DOX) via electrostatic interaction. We first clarified the boron (B)-mediated Ti valence cycle: B regulates Ti electron transfer, promotes Ti 4+ reduction to Ti 2+ , enhancing H 2 O 2 -rich tumor microenvironment Fenton-like reaction to generate cytotoxic •OH for chemodynamic therapy (CDT). Meanwhile, TiB 2 -PEG-DOX shows 53.53% photothermal conversion efficiency under 808 nm near-infrared (NIR) irradiation for efficient photothermal therapy (PTT), and NIR further triggers on-demand DOX release. DOX accumulates at tumor sites via the enhanced permeability and retention (EPR) effect to exert chemotherapy (CT). In vitro, it eliminates 86.32% of HCT-116 colorectal cancer cells via CDT/PTT/CT synergy; in vivo, it achieves nearly complete tumor ablation in mice with excellent biocompatibility. This work provides a high-performance synergistic antitumor platform and establishes a B-modulated metal valence cycling paradigm, paving the way for titanium-based nanomedicines.

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JOURNAL OF MATERIALS CHEMISTRY · 2012 ·Vol. 22 ·期 19 ·9594-9601 · IF 5.968

Synthesis and characterization of DOX-conjugated dendrimer-modified magnetic iron oxide conjugates for magnetic resonance imaging, targeting, and drug delivery

Yulei Chang,Nian Liu,Liang Chen,Xinlei Meng,Yanjing Liu,Yapeng Li,Jingyuan Wang

A tumor targeted and pH-responsive drug release system that is based on folic acid (FA) conjugated to poly(ethylene glycol) (PEG)-modified dendrimers (PAMAM) with doxorubicin (DOX) and superparamagnetic iron oxide (Fe3O4) (FA-PEG-PAMAM-DOX@IONPs) has been constructed and characterized. IONPs were stabilized by FA-PEG-G3.5 PAMAM dendrimers. The anticancer drug DOX was conjugated to the dendrimer segments of amino-stabilized IONPs using hydrazine as the linker via hydrazone bonds, which are acid cleavable and can be used as an ideal pH-responsive drug release system. The PEG moiety attached to the PAMAM@IONPs provides the conjugates with excellent solubility and stability in an aqueous medium, which may increase the circulation time. The attached FA could target the conjugates to the folate receptor (FR). These novel DOX-loaded conjugates have the potential to enhance the effect of MRI contrast and cancer therapy in the course of delivering drugs to the target sites.

CAS / MDL: 112-90-3
研究领域: 医学影像学 · 药剂学 · 肿瘤学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2016 · IF 3.902

A shell-crosslinked polymeric micelle system for pH/redox dual stimuli-triggered DOX on-demand release and enhanced antitumor activity

Lele Wang,Jing Zhang,Meijia Song,Baocheng Tian,Keke Li,Yan Liang,Jingtian Han,Zimei Wu

Based on targeted amphiphilic block copolymer N -acetyl glucosamine-poly (styrene-alt-maleic anhydride) 58 -b-polystyrene 130 (NAG-P(St-alt-MA) 58 -b-PSt 130 ), a pH/redox dual-triggered shell-crosslinked polymeric micelle system was constructed. The shell-crosslinked micelles (CLM) were prepared by post-crosslinking method to regulate drug release kinetics using cystamine as linkers between carboxy groups of the shell. Compared with non-crosslinked micelles (NCLM), CLM showed spherical shapes with little increased mean diameter of 102.40   ±   0.54   nm, low polydispersity index (PDI) of 0.19   ±   0.36, enlarged zeta potential value from −41.46   ±   0.99 to −9.31   ±   0.50   mV, indicating the successful modification of disulfide bonds in shell. In vitro drug release study clearly exhibited a pH and redox dual-sensitive drug release profile with significantly accelerated drug release under pH 5.0 and 10   mM GSH conditions (46.84% in 96   h) without burst release. Both CLM and NCLM showed quite different release profiles between physiological (pH 7.4) and tumoral microenvironment (pH 5.0), effectively avoiding the premature drug leakage and realizing on-demand drug release. The MTT assay implied that CLM presented a time- and concentration-dependent manner to inhibit proliferation of A549 and MCF-7 cells and much lower IC 50 values in comparison with that of NCLM after 72   h incubation. Both FCM and CLSM results showed that CLM displayed much higher cellular uptake efficiency and anti-tumor activities than NCLM and free DOX. CLM and NCLM could be internalized by energy-dependent endocytosis mechanism due to similar surface properties. Overall, this dual-stimuli triggered micelle system provided a promising tumor-responsive platform for cancer therapy.

研究领域: 药剂学 · 肿瘤学 · 生物材料学
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