BIOMATERIALS
·
2020
·
IF 10.317
Jing Yan,Qinghua Wu,Ziyin Zhao,Jianhua Wu,Huan Ye,Qiujun Liang,Zhuchao Zhou,Mengying Hou,Xudong Li,Yong Liu,Lichen Yin
The anticancer performance of nanomedicine is largely impeded by insufficient intratumoral penetration. Herein, tumor microenvironment (TME)-amendatory and self-adaptive nanoclusters (NCs) capable of cancer-associated fibroblasts (CAFs) depletion and size/charge conversion were engineered to mediate light-assisted, hierarchical intratumoral penetration. Particularly, large-sized NCs (~50 nm) were prepared via self-assembly of FAP-α-targeting peptide-modified, 1 O 2 -sensitive polymers, which were further used to envelope small-sized dendrimer (~5 nm) conjugated with Ce6 and loaded with DOX (DC/D). After systemic administration, the NCs efficiently targeted CAFs and generated lethal levels of 1 O 2 upon light irradiation, which depleted CAFs and concomitantly dissociated the NCs to liberate small-sized, positively charged DC/D. Such stroma attenuation and NCs transformation collectively facilitated the delivery of DC/D into deeper regions of CAF-rich tumors, where DOX and 1 O 2 provoked synergistic anti-cancer efficacies. This study provides an effective approach to facilitate the tumor penetration of nanomedicine by concurrently and spatiotemporally reconfiguring the nano-properties and remodeling the TME.
研究领域:
纳米技术
·
癌症治疗
·
药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2025
·
IF 11.9
Zhiyuan Tang,Yuening Sun,Quanhua Yi,Qian Ding,Yang Ding,Jianfei Huang
The effective intracellular accumulation of doxorubicin (DOX) is crucial for improving antitumor efficacy, which is severely impeded by limited drug penetration, uncontrollable drug release, and drug resistance. In this study, a thermal-deformative polymer embedding ultrasmall ceria (CeO 2 ) was rationally designed for deep tumor drug shuttling and hypoxia reversal to improve chemotherapy. Structurally, the CeO 2 nanozyme was covalently grafted with a polymer of p(NIPAM-co-AM) that could sharply shrink for DOX loading, which was consolidated with polydopamine (PDA) film encapsulation. Thereafter, a tumor penetration guide of apolipoprotein A-I (apoA-I) conjugated iRGD peptide (apoA-I-iRGD) was further decorated onto the PDA shell via Michael addition for preparing CeO 2 P/DOX@iAPDA. With the aid of apoA-I-iRGD, CeO 2 P/DOX@iAPDA penetrated both the tumor spheroids (∼78 μm) and the tumors of the mouse model deeply. After internalization by tumor cells and triggering by low pH in lysosomes, rapid DOX release was achieved by peeling off the PDA shell and thermosensitive deformation of p(NIPAM-co-AM). CeO 2 P/DOX@iAPDA provided 66.4% tumor suppression in 4T1-derived tumor spheroids and 63.2% in 4T1-tumor-bearing mice, respectively. Preliminary mechanistic research involving western blotting and immunohistochemistry revealed that CeO 2 P/DOX@iAPDA reversed resistance through the through HIF-1α-P-gp/lipid axis. Collectively, this study intelligently integrated CeO 2 nanozymes, temperature-sensitive polymers, and imitated biochemical modifications to improve chemotherapy for breast cancer.
研究领域:
纳米技术
·
癌症治疗
·
药学科学
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生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2018
·
IF 5.08
Meng Li,Ying Wang,Huiming Lin,Fengyu Qu
Here, hollow CuS nanocubes about 250–300 nm in size were synthesized based on the Kirkendall effect by using CuO nanocubeas precursor and template. The reactant concentration and reaction time could be adopted to adjust the final composition and hollow structure. The as-synthetic CuS nanocube was assembled by a great deal of nanoparticles (15–20 nm), making abundant porous structure in the shell layer. The localized surface plasmon resonance and the novel porous hollow structure (improve light reflex) further make sure the enhanced Near-infrared (NIR) light absorption as well as photothermal conversion efficiency (30.3%). Moreover, the mechanism of reactive oxygen species (ROS) generation was investigated in detail, revealing that the released Cu + ion and the oxygen are the determined factors. To further improve the monodispersity and biocompatibility, PEG-NH 2 modified nanostructure (CuS@PEG) was prepared and it possessed high loading efficiency to doxorubicin hydrochloride (DOX). Moreover, DOX-CuS@PEG reveals the acid and NIR sensitive-release performance. The synergistic effect of chemotherapy associated with photothermal therapy (PTT) and photodynamic therapy (PDT) display the enhanced specific cytotoxicity to cancer cells.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2019
·Vol. 7
·期 5
·1825-1832
·
IF 5.251
Luying Shen,Shan Pan,Dechao Niu,Jianping He,Xiaobo Jia,Jina Hao,Jinlou Gu,Wenru Zhao,Pei Li,Yongsheng Li
As drug-delivery carriers for cancer chemotherapy, gatekeeper-capped mesoporous silica nanoparticles (MSNs) have been widely studied due to their high drug-loading capability, controlled drug release property and good biocompatibility. However, the currently reported gatekeeper-capped MSNs suffer from complex synthetic procedures, potential toxicity of gatekeepers, unsatisfactory control on drug stimuli-release, etc. In this work, we develop a simple but efficient approach to fabricate PEGylated organosilica-capped mesoporous silica nanoparticles (POMSNs) by employing a disulfide-doped organosilica coating as the gatekeeper formed by the hydrolysis and condensation of a silane coupling agent 3-(mercaptopropyl)trimethoxysilane (MPTMS) to block the mesopores of MSNs. Owing to the glutathione (GSH)-responsive biodegradation behavior of the disulfide-doped organosilica gatekeeper, the DOX-loaded POMSNs exhibit only 20% cell viability towards SMMC-7721 tumor cells, and almost no toxicity towards L-02 cells at a DOX concentration of 50 μg mL−1 was measured, demonstrating their selective cytotoxicity in vitro. More importantly, it is demonstrated that the DOX-loaded POMSNs exhibit a tumor inhibition rate of 71.3% and negligible systematic toxicity. Consequently, the resultant POMSNs show great potential as drug nanocarriers for redox-responsive drug release and passive-targeting tumor chemotherapy.
研究领域:
纳米技术
·
药学
·
癌症研究
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Shudi Yang,Ying Wang,Zhaoxiang Ren,Mengtian Chen,Weiliang Chen,Xuenong Zhang
In this research, a charge-conversional polymer, poly- l -lysine-lipoic acid (PLL-LA), was prepared by dimethylmaleic anhydride (DA) modification and applied as a carrier with enhanced cell internalization and intracellular pH- and reduction-triggered doxorubicin (Dox) release. The surface charge of dimethylmaleic anhydride-poly- l -lysine-lipoic acid micelles (DA-PLL-LA) was negative at physiological pH and reversed to positive at the extracellular and intracellular pH of cancer cells. At tumor extracellular pH of 6.8, the conjugates underwent a rapid charge-reversible process with almost 80% DA cleavage within 2 h, and then endocytosed into the endo/lysosomes more rapidly than at physiological pH of 7.4. The Dox/DA-PLL-LA micelles (Dox-micelles) demonstrated a sustained drug release in vitro under physiological condition, and rapid Dox release was triggered by both extracellular pH and high-concentration reducing glutathione. The Dox-micelles also exhibited enhanced internalization at extracellular pH, rapid intracellular drug release, and improved cytotoxicity against A549 cells in vitro . Excellent tumor-penetrating efficacy was also found in A549 tumor spheroids and solid tumor slices. Moreover, the DA-PLL-LA micelles exhibited excellent tumor-targeting ability in tumor tissues and excellent antitumor efficacy and low systemic toxicity in breast tumor-bearing mice. Therefore, the DA-PLL-LA micelles demonstrated great potential for targeted and efficient drug delivery in cancer treatments.
研究领域:
药学
·
生物医学工程
·
癌症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 20
·9707-9719
·
IF 7.233
Jia Zhou,Tianliang Li,Chunlei Zhang,Junyuan Xiao,Daxiang Cui,Yingsheng Cheng
Multifunctional nanoplatforms have been developed into advanced drug delivery systems for cancer therapy. In this study, we report a charge-switchable nanocapsule with multistage pH-responsive behaviors. First, DOX-encapsulated and oleylamine-embedded hollow structures with a diameter of 132 ± 21 nm are prepared via the double emulsion method. Subsequently, the hollow structures are encompassed by Gd-DTPA-, chlorin e6 (Ce6)-, and folate (FA)-modified BSA to form tumour-targeted, dual NIR/MR imaging-guided and chemo–photodynamic therapeutic nanoplatforms. Importantly, the nanocapsule can intelligently switch its surface charge to positive under mildly acidic conditions (pH 6.5) with no release of Ce6 and DOX, which is confirmed by ξ-potential and cumulative release measurements. Moreover, confocal imaging pictures demonstrate that acid-sensitive DOX sealed in nanocapsules is progressively released into the nuclei of MGC-803 cells. These advantages as well as FA-targeting facilitate effective endocytosis and synergistic therapeutic efficacy. Selective tumour accumulation and long tumour retention time are further indicated by NIR/MR in vivo imaging. In addition, excellent therapeutic efficacy combined with chemotherapy (DOX) and photodynamic therapy (PDT) is observed with the tumour eventually ablating at the 15th day. All results demonstrate that the as-prepared nanocapsules hold great potential for clinical cancer theranostics.
研究领域:
癌症治疗
·
药物递送系统
·
纳米技术
·
成像技术
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiangshu Cheng,Ping Zhou,Changmei Chen,Fengyuan Liu,Lulu Wang,Rongchun Yi,Chao Yu,Tao Deng
Carbon dots (CDs) have been extensively studied in tumor therapy due to their excellent compatibility, remarkable stability, and luminescent properties. However, CDs-based therapeutic agents often face limitations such as rapid clearance, poor targeting, and weak responsiveness, which hinder their efficacy in achieving precise tumor treatment. To address these challenges, this study presents the construction of a dual-targeting, dual-responsive drug delivery platform with hierarchical structures: MV-DNA-CDs@DOX. Firstly, methacrylic acid-coated o-phenylenediamine carbon dots were synthesized using methacrylic acid and o-phenylenediamine. This was then conjugated with an i-motif-containing DNA sequence to create DNA-CDs with a “yarn ball-like” secondary structure. The nano-particles preserved the acid-responsive nature of the sequence and introduced an additional photo-responsive characteristic, enhancing the nanocarrier’s ability to deliver drugs deeply into tumor tissues. Upon loading with DOX, the polymeric nanocarrier was subject to biomimetic treatment, endowing it with active tumor-targeting capabilities and improving the specific distribution of the drug within tumor sites. Therefore, the use of biocompatible and responsive DNA segments as crosslinkers to construct organic nanopolymer carriers in the preparation of anti-tumor nanomaterials holds promise in expanding the application of nanotechnology in the field of cancer treatment.
研究领域:
纳米技术
·
癌症治疗
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Lipeng Qiu,Mengqin Zhu,Kai Gong,Huanhuan Peng,Lu Ge,Li Zhao,Jinghua Chen
2-(Octadecyloxy)-1,3-dioxan-5-amine (OD) with an acid degradable ortho ester group was synthesized, and conjugated to hyaluronic acid (HA) backbone to prepare pH-responsive and tumor-targeted hyaluronic acid-2-(octadecyloxy)-1,3-dioxan-5-amine (HOD) conjugates. 1 H NMR was used to confirm the structures of the OD and HOD. The studies of pH-responsive behavior showed that HOD micelles were stable under physiological conditions while they were degraded in the tumor acidic microenvironment. Doxorubicin (DOX)-loaded HOD micelles (DOX/HOD) with a narrow size distribution were prepared and characterized. The increased release of DOX from DOX/HOD micelles was presented at low pH condition. From in vitro cytotoxicity assays against MCF-7 cells, the blank micelles exhibited low cytotoxicity, but DOX/HOD micelles had the higher cytotoxicity than pH insensitive control and free DOX. Cellular uptake experiments and confocal images demonstrated that pH-sensitive DOX/HOD micelles could be internalized efficiently by CD44 receptor mediated endocytosis, and then DOX was rapidly released due to pH-induced degradable of OD to cell nucleus compared to the non-sensitive micelles. Furthermore, endocytosis inhibition studies presented that DOX/HOD micelles were internalized into cells mainly via caveolae-mediated routes. In vivo study of micelles in tumor-bearing mice indicates that HOD micelles were more effectively accumulated into the tumor tissue than HOA micelles. These results verify that the pH-sensitive HOD micellar system is a promising nanocarrier for enhanced internalization of antitumor drugs to cancer cells.
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
Small
·
2016
·Vol. 12
·期 31
·4286-4298
·
IF 8.315
Qi Lei,Wen-Xiu Qiu,Jing-Jing Hu,Peng-Xi Cao,Cheng-Hui Zhu,Han Cheng,Xian-Zheng Zhang
In this work, a matrix metalloproteinase (MMP)-triggered tumor targeted mesoporous silica nanoparticle (MSN) is designed to realize near-infrared (NIR) photothermal-responsive drug release and combined chemo/photothermal tumor therapy. Indocyanine green (ICG) and doxorubicin (DOX) are both loaded in the MSN modified with thermal-cleavable gatekeeper (Azo-CD), which can be decapped by ICG-generated hyperthermia under NIR illumination. A peptidic sequence containing a short PEG chain, matrix metalloproteinase (MMP) substrate (PLGVR) and tumor cell targeting motif (RGD) are further decorated on the MSN via a host–guest interaction. The PEG chain can protect the MSN during the circulation and be cleaved off in the tumor tissues with overexpressed MMP, and then the RGD motif is switched on to target tumor cells. After the tumor-triggered targeting process, the NIR irradiation guided by ICG fluorescence can trigger cytosol drug release and realize combined chemo/photothermal therapy.
研究领域:
纳米技术
·
癌症治疗
·
材料科学
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Yajing Wang,Wennan Yan,Ji Zhang,Ziyi Li,Yingshu Guo
Starvation therapy mediated by glucose oxidase is a widely used therapeutic approach for tumor treatment, but it is limited by the simultaneous drawbacks of weak therapeutic efficacy, nonspecificity, and systemic toxicity. Thus, combination therapy was used to complement the widely used therapeutic strategy for anticancer therapy. On the basis of starvation therapy, we designed a catalytic model of nanosheets with biological cascade enzymes synergizing with anticancer drugs. In short, two cascade enzymes (glucose oxidase and horseradish peroxidase) are covalently immobilized on Ti3C2 MXene nanosheet and a cascade enzyme nanoreactor is formed by electrostatically adsorbing positive charged DOX. Finally, the outer layer is coated with hyaluronic acid. By combining glucose oxidase-mediated starvation therapy, photothermal therapy, and chemotherapy, we have achieved the therapeutic effect of “killing three birds with one stone” by combining the dual stimulation response of endogenous and exogenous sources to the tumor site. This method not only achieves the targeting of cancer cells but also improves the systemic toxicity and reduced efficacy of biological enzymes and realizes synergistic cancer therapy with enhanced cascade reactions. It opens up a new path for the research of nanomedicine.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Meitao Duan,Dan Zhou,Junfang Ke,Yan Chen,Wenfeng Wu,Yue Li,Jungang Ren,Li Wang,Zhiqiang Zhang,Chen Wang
Receptor and ligand binding mediated targeted drug delivery systems (DDS) sometimes fail to target to tumor sites, and cancer cell membrane (CCM) coating can overcome the dilemma of immune clearance and nonspecific binding of DDS in vivo. In order to enhance the targeting ability and improve the anti-tumor effect, a dual targeting DDS was established based on U87MG CCM mediated homologous targeting and cyclic peptide RGD mediated active targeting. The DDS was prepared by coating RGD doped CCM onto doxorubicin (DOX) loaded liposomes. The homologous and active dual targeting ability endowed the DDS (RGD-CCM-LP-DOX) exhibited superior cancer cell affinity, improved tissue distribution and enhanced anti-tumor effects. In vivo pharmacodynamic studies revealed that RGD-CCM-LP-DOX exhibited superior therapeutic effect compared with homologous targeting CCM-LP-DOX and non-targetable LP-DOX injection. H&E staining, Ki 67 staining and TUNEL staining confirmed that RGD-CCM-LP-DOX not only increased anti-tumor efficacy, but also reduced tissue toxicity by changing the distribution in vivo . The experimental results showed that the RGD doped CCM camouflaged liposome DDS is a better choice for chemotherapeutics delivery.
研究领域:
药学
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2021
·
IF 9.229
Miao Deng,Rong Guo,Shuya Zang,Jingdong Rao,Mengmeng Li,Xian Tang,Chunyu Xia,Man Li,Zhirong Zhang,Qin He
Natural killer (NK) cell-based immunotherapy presents a promising antitumor strategy and holds potential for combination with chemotherapy. However, the suppressed NK cell activity and poor tumor retention of therapeutics hinder the efficacy. To activate NK cell-based immuno–chemotherapy and enhance the tumor retention, we proposed a pH-responsive self-aggregated nanoparticle for the codelivery of chemotherapeutic doxorubicin (DOX) and the transforming growth factor-β (TGF-β)/Smad3 signaling pathway inhibitor SIS3. Polycaprolactone-poly(ethylene glycol) (PCL-PEG2000) micelles modified with dibenzylcyclooctyne (DBCO) or azido (N3) and coated with acid-cleavable PEG5000 were established. This nanoplatform, namely, M-DN@DOX/SIS3, could remain well dispersed in the neutral systemic circulation, while quickly respond to the acidic tumor microenvironment and intracellular lysosomes, triggering copper-free click reaction-mediated aggregation, leading to the increased tumor accumulation and reduced cellular efflux. In addition, the combination of DOX with SIS3 facilitated by the aggregation strategy resulted in potent inhibition of melanoma tumor growth and significantly increased NK cells, NK cell cytokines, and antitumor T cells in the tumor. Taken together, our study offered a new concept of applying copper-free click chemistry to achieve nanoparticle aggregation and enhance tumor retention, as well as a promising new combined tumor treatment approach of chemotherapy and immunotherapy.
研究领域:
癌症研究
·
纳米技术
·
免疫疗法
·
化疗
·
药学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）