Pharmaceutics
·
2023
·Vol. 15
·期 7
·2014
·
IF 5.4
Fang Luo,Ting Zhong,Ying Chen,Qianqian Guo,Ling Tao,Xiangchun Shen,Yanhua Fan,Xingjie Wu
Dual-ligand targeting drug delivery nanoplatforms are considered a promising tool for enhancing the specificity of chemotherapy. However, serious off-target delivery has been observed in current dual-ligand targeting nanoplatforms, as each ligand can independently recognize receptors on the cell membrane surface and guide drug nanocarriers to different cells. To overcome this barrier, a dual-ligand synergistic targeting (DLST) nanoplatform is developed, which can guide chemotherapy treatment specifically to cancer cells simultaneously overexpressing two receptors. This nanoplatform consists of a singlet oxygen (1O2) photosensitizer-loaded nanocarrier and a drug-loaded nanocarrier with1O2responsiveness, which were, respectively, decorated with a pair of complementary DNA sequences and two different ligands. For cancer cells overexpressing both receptors, two nanocarriers can be internalized in larger quantities to cause DNA hybridization-induced nanocarrier aggregation, which further activates1O2-triggered drug release under light irradiation. For cells overexpressing a single receptor, only one type of nanocarrier can be internalized in a large quantity, leading to blocked drug release due to the ultrashort action radius of1O2. In vivo evaluation showed this DLST nanoplatform displayed highly specific tumor treatment with minimized long-term toxicity. This is a highly efficient drug delivery system for DLST chemotherapy, holding great potential for clinical applications.Keywords:synergistic targeting;specific treatment;drug delivery;controlled release;tumor chemotherapy
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Chao Li,Chihamo Jike,Yan Song,Guo Liang Li,Yi Jia,Junbai Li
Materials with cascade-responsive self-healing similar to that of living organisms can be of great practical value. Herein, a synthetic polymeric material is demonstrated that can achieve cascade-responsive self-healing via a mechanical-force-triggered self-crosslinking reaction. Ferrocene (Fc) is used as a mechanophore, and its decomposition when the material is subjected to a mechanical force generates Fe 3+ , which forms a complex with catechol residues present in side chains; thus, forming a new network structure. This cross-linking results in the tensile strength of CRSP-3 recovered completely after compression at 50 MPa for 5 min and standing for 72 h at room temperature. This strategy also provides the material with self-strengthening ability under repeated mechanical loading. The material exhibits the ability to resist the diffusion of micro cracks caused by high pressure in seawater. This study provides design principles for the construction of a new generation of intelligent bio-like self-healing materials.
研究领域:
材料科学
·
化学
·
仿生学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Qingye Meng,Shuangling Zhong,Jia Wang,Yan Gao,Xuejun Cui
Controlled and accurate drug release at the target site have been the focus of research. Especially in cancer therapy, economical, convenient and accurate delivery strategies could help to reduce the toxic effects of drugs on normal tissues and improve drug availability. In the study, glutathione (GSH)-responsive microcapsules (FA-RSMCs) were prepared by sonochemical method based on thiolated modified starch . 10-Hydroxycamptothecin (HCPT) was designed as a reactive oxygen species (ROS)-responsive polyprodrug (polyHCPT), which was loaded into the core of the microcapsules to obtain stepwise released drug delivery carriers. In the tumor microenvironment, FA-RSMCs first triggered GSH-responsive cleavage to release polyHCPT, followed by ROS-responsive cleavage of polyHCPT to release intact HCPT drug molecules. The results of experiments in simulated tumor microenvironment showed that FA-RSMCs exhibited good cascade-response release properties in vitro . It exhibited good anti-tumor ability and protection of normal cells in cytotoxicity in vitro . This strategy enhanced the accuracy and safety of targeted delivery of HCPT via microcapsules, which has potential for clinical application.
研究领域:
药剂学
·
肿瘤学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-18
·
IF 10.435
Li Fan,Liang Yan,Wang Miaochen,Xu Xing,Zhao Fen,Wang Xu,Sun Yong,Chen Wantao
Synergistic chemo-photodynamic therapy has garnered attention in the field of cancer treatment. Here, a pH cascade-responsive micellar nanoplatform with nucleus-targeted ability, for effective synergistic chemo-photodynamic cancer treatment, was fabricated. In this micellar nanoplatform, 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (Por), a photodynamic therapy (PDT) agent was utilized for carrying the novel anticancer drug GNA002 to construct a hydrophobic core, and cyclic RGD peptide (cRGD)-modified polyethylene glycol (PEG) (cRGD-PEG) connected the cell-penetrating peptide hexaarginine (R 6 ) through a pH-responsive hydrazone bond (cRGD-PEG-N = CH-R 6 ) to serve as a hydrophilic shell for increasing blood circulation time. After passively accumulating in tumor sites, the self-assembled GNA002-loaded nanoparticles were actively internalized into cancer cells via the cRGD ligands. Once phagocytosed by lysosomes, the acidity-triggered detachment of the cRGD-PEG shell led to the formation of R 6 -coated secondary nanoparticles and subsequent R 6 -mediated nucleus-targeted drug delivery. Combined with GNA002-induced nucleus-specific chemotherapy, reactive oxygen species produced by Por under 532-nm laser irradiation achieved a potent synergistic chemo-photodynamic cancer treatment. Moreover, our in vitro and in vivo anticancer investigations revealed high cancer-suppression efficacy of this ideal multifunctional nanoplatform, indicating that it could be a promising candidate for synergistic anticancer therapy.
研究领域:
纳米技术
·
肿瘤学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano-Micro Letters
·
2020
·Vol. 12
·期 1
·1-18
·
IF 12.264
Li Yang,Lin Jinyan,Wang Peiyuan,Luo Qiang,Zhu Fukai,Zhang Yun,Hou Zhenqing,Liu Xiaolong,Liu Jingfeng
A pH/ROS cascade-responsive carrier-free nanodrug with self-targeting activation and ROS regeneration abilities.
On-demand release of VES in response to intracellular ROS to accelerate drug release via positive-feedback loop.
Highly synergistic therapeutic efficiency via orchestrated cooperation of oxidation-chemotherapy.
研究领域:
癌症研究
·
纳米医学
·
药剂学
·
诊疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2019
·Vol. 17
·期 1
·1-18
·
IF 5.345
Niu Shiwei,Williams Gareth R.,Wu Jianrong,Wu Junzi,Zhang Xuejing,Chen Xia,Li Shude,Jiao Jianlin,Zhu Li-Min
Background It is extremely difficult to develop targeted treatments for triple-negative breast (TNB) cancer, because these cells do not express any of the key biomarkers usually exploited for this goal.Results In this work, we develop a solution in the form of a cascade responsive nanoplatform based on thermo-sensitive poly(N-vinylcaprolactam) (PNVCL)-chitosan (CS) nanoparticles (NPs). These are further modified with the cell penetrating peptide (CPP) and loaded with the chemotherapeutic drug doxorubicin (DOX). The base copolymer was optimized to undergo a phase change at the elevated temperatures of the tumor microenvironment. The acid-responsive properties of CS provide a second trigger for drug release, and the inclusion of CPP should ensure the formulations accumulate in cancerous tissue. The resultant CPP-CS-co-PNVCL NPs could self-assemble in aqueous media into spherical NPs of size < 200 nm and with low polydispersity. They are able to accommodate a high DOX loading (14.8% w/w). The NPs are found to be selectively taken up by cancerous cells both in vitro and in vivo, and result in less off-target cytotoxicity than treatment with DOX alone. In vivo experiments employing a TNB xenograft mouse model demonstrated a significant reduction in tumor volume and prolonging of life span, with no obvious systemic toxicity.Conclusion sThe system developed in this work has the potential to provide new therapies for hard-to-treat cancers.
研究领域:
药学
·
癌症研究
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Fangying Yu,Xuwei Shang,Yun Zhu,Haiya Lou,Yupeng Liu,Tingting Meng,Yun Hong,Hong Yuan,Fuqiang Hu
Early antitumor therapy is an important determinant of survival in patients with cancer. Utilization of specific pathological states, such as hypoxia, greatly promotes the development of intelligent drug delivery systems (DDSs) for targeted antitumor therapy. However, a slight decrease in oxygen levels in early-stage tumors is not sufficient to trigger hypoxia-responsive drug release. Nitroreductase (NTR) is overexpressed in bioreductive hypoxic cancers, and its expression level has been verified to be directly related to hypoxic status. Herein, using glucose oxidase (GOx) as an O 2 -consuming agent to exacerbate hypoxia, a cascade strategy of GOx-induced overexpression of NTR and amplified NTR-catalyzed release was proposed for early antitumor therapy. Briefly, NTR-sensitive p-nitrobenzyl chloroformate (PNZ-Cl) was adopted to conjugate with the polysaccharide chitosan (CS) and self-assemble into CS-PNZ-Cl micelles . These polymer micelles possess the dual abilities to specifically immobilize GOx and load mitoxantrone (MIT) to form the NTR-responsive nanocascade reactor GOx/ [email protected] First, as a “key”, tumor hypoxia triggers the initial release of GOx, which serves as the O 2 -consuming agent when catalyzing its reaction with glucose, which is accompanied by H 2 O 2 production. Depleted oxygen levels facilitate the expression of NTR, which in turn amplifies the capacity of the nanocascade reactor to decompose into secondary micelles for enhanced intratumoral permeation . GOx-inspired NTR amplification further elicits MIT release, realizing a synergistic “domino effect” cascade. In addition, upregulated H 2 O 2 has been shown to effectively reverse GSH-mediated MIT resistance, reaching the superior tumor inhibition rate of 93.08%. This GOx-based NTR-responsive nanocascade reactor provides amplification of the bioreductive hypoxic tumor microenvironment for early antitumor therapy.
研究领域:
药理学
·
肿瘤学
·
生物医学工程
·
化学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY OF MATERIALS
·
2017
·
IF 9.466
Liangliang Dai,Ruisi Cai,Menghuan Li,Zhong Luo,Yonglin Yu,Weizhen Chen,Xinkun Shen,Yuxia Pei,Xiaojing Zhao,Kaiyong Cai
This study reports a cascade-responsive disassemble micellar drug delivery system with dual-targeting potential (cell and mitochondria targeting), which optimizes the distribution of antitumor drugs on systemic, local, and subcellular levels to enhance antitumor efficacy. A new cationic porphyrin derivative 5-(3-hydroxy-p-(4-trimethylammonium)butoxyphenyl)-10,15,20-triphenylporphyrin chlorine (MTPP) is synthesized as a mitochondria-targeting photosensitizer. After accumulating at a tumor site, the micellar nanosystem is endocytosed by tumor cells facilitated by the folate receptor-mediated pathway. Then, the hydrophobic PDEA block would be protonated in intracellular acidic endo-/lysosomes and promote the escape of prodrug micelles from endo-/lysosome to cytoplasm, resulting in the first-stage destabilization of micelles. Subsequently, the CPT is released in response to high concentration of GSH in cytoplasm, which would greatly increase the hydrophilicity of the BOH block and initiate the complete disassembly of the polymer micelles owing to the damage of the hydrophilic–hydrophobic balance. Additionally, the released MTPP is selectively accumulated in mitochondria and activates mitochondria apoptotic pathway upon light irradiation as a result of ROS generation. Both in vitro and in vivo studies indicate that the polymeric micelle not only effectively improves the targeted delivery efficiency but also dramatically enhances the combinational antitumor efficacy while reducing the side effects associated with the laser irradiation and mitochondria-targeted tumor therapy.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2021
·
IF 12.479
Liangliang Dai,Xiang Li,Xinmin Zheng,Zhenxiang Fu,Mengjiao Yao,Siyu Meng,Jiangong Zhang,Binbin Han,Quanli Gao,Jing Chang,Kaiyong Cai,Hui Yang
Immunosuppressive tumor microenvironment and low delivery efficiency severely impede the tumor chemotherapy effect. To address this issue, we develop a pH/ROS cascade-responsive prodrug micelle to deliver siTGF-β with size-shrinkage and charge-reversal property, leading to synergistical tumor microenvironment remodeling. The nanosystem highly improved endocytosis efficiency and tumor penetration depth through charge reversal and size reduction upon exposure to weakly acidic tumor microenvironment. Moreover, the nanocarrier would rapidly escape from endo/lysosome, disassemble and release siTGF-β and hydroxycamptothecin in response to high intracellular ROS. Furthermore, the nanosystem significantly boosted antitumor immune response and reduced immune tolerance with remodeling tumor microenvironment, which significantly prolonged the survival time of tumor-bearing mice (75% survival rate upon 35 days). It is realized by the combined effects of chemotherapy-enhanced immunogenicity and recruitment of effector T cells , TGF-β-blockade immunotherapy-activated inhibition immunosuppressive tumor microenvironment and epithelial-to-mesenchymal transition (EMT), and regulation physical tumor microenvironment via reducing the dense tumor extracellular matrix and the high tumor interstitial pressure obstacles. To this end, the nanosystem not only overcame biobarriers and reinforced antitumor immune response, but also effectively inhibited tumor growth, metastasis and recurrence in vivo .
研究领域:
肿瘤学
·
药学
·
纳米技术
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Liangliang Dai,Xiang Li,Mengjiao Yao,Peiyun Niu,Xichen Yuan,Ke Li,Maowen Chen,Zengxiang Fu,Xianglong Duan,Haibin Liu,Kaiyong Cai,Hui Yang
IDO blockade-based immunotherapy has been impeded by the activation of antitumor immune response and low delivery efficiency of immunotherapeutic, resulting from natural biological barriers and immune resistance. Herein, a programmable drug delivery nanosystem with enhanced tumor penetration and endocytosis is constructed for chemotherapy-enhanced immunotherapy by loading immune checkpoint IDO inhibitor NLG919 in pH/redox cascade-responsive prodrug micelle . The nanosystem shrinked micelles sizes and converted charge from negative to positive for enhanced tumor penetration and endocytosis in responding to the weakly acidic tumor microenvironment . The endocytosed nanosystem dramatically disassembled and released curcumin and NLG919 in redox-rich cytoplasm. In vitro and in vivo studies demonstrate that the nanosystem not only effectively overcame biological barriers, but also significantly boosted antitumor immune response and reduced immune resistance. It was realized by the combined effects of chemotherapy-enhanced immunogenicity , and NLG919-induced IDO-blockade immunotherapy, consequently inhibiting tumor growth, metastasis and recurrence with high efficiency in vivo . The study offers a nanoplatform with deep tumor penetration, high cellular uptake and effective antitumor immune response for the advance of chemo-immunotherapy.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2020
·
IF 14.588
Ke Li,Chuanchuan Lin,Ye He,Lu Lu,Kun Xu,Bailong Tao,Zengzilu Xia,Rui Zeng,Yulan Mao,Zhong Luo,Kaiyong Cai
As an increased product of high-rate aerobic glycolysis in tumors, lactate could regulate the immunosuppressive tumor microenvironment (TME). A PEG-CDM surface modified, GSH-dependent responsive hollow mesoporous organosilica nanoplatform loaded with hydroxycamptothecin (HCPT) and siMCT-4 was administrated for synergistic tumor chemo-immunotherapy. The nanoplatform cascaded responded to the weak acid TME and the high level of GSH in tumor cells. HCPT and siMCT-4 were continuously released from the nanoplatform for chemotherapy and inhibiting intracellular lactate efflux. The increased intracellular lactate and HCPT effectively induced tumor cell apoptosis. Moreover, the decreased extracellular lactate polarized tumor-associated macrophages (TAMs) phenotype from M2 type to M1 type and restored CD8+ T cell activity in vivo. The results demonstrated that the nanoplatform effectively removed the immunosuppressive TME, inhibited tumor growth, and suppressed lung metastasis of B16F10 cells and 4T1 cells via the combination of inhibiting lactate efflux and chemotherapy. Accordingly, it suggested a strategy to transform immunosuppressive tumors into “hot” tumors and inhibit the tumor growth with high efficiency in vivo.
研究领域:
纳米技术
·
肿瘤学
·
药学
·
免疫治疗
·
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）