JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-20
·
IF 10.2
Dong Lanlan,Huang Can,Zhao Baohua,Hu Guangyun,Huang Yong,Zhang Xiaorong,Hu Xiaohong,Wang Ying,XiaoyanSun,Qian Wei,Luo Gaoxing
Suppressing persistent multidrug-resistant (MDR) bacterial infections and excessive inflammation is the key for treating chronic wounds. Therefore, developing a microenvironment-responsive material with good biodegradability, drug-loading, anti-infection, and anti-inflammatory properties is desired to boost the chronic wounds healing process; however, using ordinary assembly remains a defect. Herein, we propose a pH/enzyme dual-responsive polymyxin B (PMB) spatiotemporal-release hydrogel (GelMA/OSSA/PMB), namely, the amount of OSSA and PMB released from GelMA/OSSA/PMB was closely related the wound pH and the enzyme concentration changing. The GelMA/OSSA/PMB showed better biosafety than equivalent free PMB, owing to the controlled release of PMB, which helped kill planktonic bacteria and inhibit biofilm activity in vitro. In addition, the GelMA/OSSA/PMB exhibited excellent antibacterial and anti-inflammatory properties. A MDR Pseudomonas aeruginosa caused infection was effectively resolved by the GelMA/OSSA/PMB hydrogel in vivo, thereby significantly boosting wound closure during the inflammatory phase. Furthermore, GelMA/OSSA/PMB accelerated the sequential phases of wound repair.
研究领域:
生物医学工程
·
材料科学
·
药物学
·
伤口愈合
·
传染病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2015
·
IF 8.557
Yang Wang,Ruibo Zhao,Shibing Wang,Zhaoming Liu,Ruikang Tang
Multidrug resistance is one of major obstacles to the effective cancer chemotherapy. To address this issue, we developed the effective circumvention of multidrug resistance in cancer cells by a yolk-shell Fe 3 O 4 @MgSiO 3 nanoplatform with the polymerpoly(ethylene glycol) and folic acid modifications can achieve active targeted delivery of anti-cancer drug by using combined magnetic and ligand targeting . The direct intracellular drug delivery of doxorubicin by nanocarrier was much more effectively than free DOX for multidrug resistant Hep-G2/MDR cancer cells. Besides the excellent biocompatibility, high drug loading efficiency, dual-targeting delivery, and controlled releasing behavior, in vivo experiments demonstrate that this nanocarrier can specifically deliver and concentrate doxorubicin hydrochloride in tumor sites to overcome drug resistance. It follows an alternative strategy for effective chemotherapy against drug resistant cancers by using rationally designed nanomaterial .
研究领域:
癌症研究
·
纳米技术
·
药学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2011
·
IF 7.883
Feihu Wang,Dianrui Zhang,Qiang Zhang,Yuxuan Chen,Dandan Zheng,Leilei Hao,Cunxian Duan,Lejiao Jia,Guangpu Liu,Yue Liu
Multidrug resistance (MDR) in tumor cells is a significant obstacle for successful cancer chemotherapy. Overexpression of drug efflux transporters such as P-glycoprotein (P-gp) is a key factor contributing to the development of tumor drug resistance. Verapamil (VRP), a P-gp inhibitor, has been reported to be able to reverse completely the resistance caused by P-gp. For optimal synergy, the drug and inhibitor combination may need to be temporally colocalized in the tumor cells. Herein, we investigated the effectiveness of simultaneous and targeted delivery of anticancer drug, paclitaxel (PTX), along with VRP, using DOMC-FA micelles to overcome tumor drug resistance. The floate-functionalized dual agent loaded micelles resulted in the similar cytotoxicity to PTX-loaded micelles/free VRP combination and co-administration of two single-agent loaded micelles, which was higher than that of PTX-loaded micelles. Enhanced therapeutic efficacy of dual agent micelles could be ascribe to increased accumulation of PTX in drug-resistant tumor cells. We suggest that the synergistic effect of folate receptor-mediated internalization and VRP-mediated overcoming MDR could be beneficial in treatment of MDR solid tumors by targeting delivery of micellar PTX into tumor cells. As a result, the difunctional micelle systems is a very promising approach to overcome tumor drug resistance.
研究领域:
药学科学
·
肿瘤学
·
药物递送系统
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Jing Zhang,Di Zhang,Qian Li,Yue Jiang,Aixin Song,Zhonghao Li,Yuxia Luan
Potentiating systemic immunity against breast cancer is in the most urgent demand as breast cancer is less sensitive to immune checkpoint blockade. Although phototherapy and some chemotherapy can trigger immunogenic cell death (ICD) for T cell-mediated antitumor immune response, their immunotherapy efficacy is severely restricted by insufficient phototherapeutic capability and severe multidrug resistance (MDR). Inspired by both the hypersensitivity to phototherapy and the key role of MDR for mitochondria, a rationally engineered immunity amplifier via mitochondria-targeted photochemotherapeutic nanoparticles was, for the first time, achieved to fight against low-immunogenic breast cancer without additional immune agents. The newly synthesized task-specific mitochondria-targeted IR780 derivative (T780) was integrated with chemotherapeutic doxorubicin (DOX) to form multifunctional nanoparticles via an assembling strategy along with bovine serum albumin (BSA) as a biomimetic corona (BSA@T780/DOX NPs). The in situ enhancement in both phototherapy and MDR reversal by targeting mitochondria with BSA@T780/DOX NPs boosted highly efficient ICD toward excellent antitumor immune response. The newly developed strategy not only eradicated the primary tumor but also eliminated the bilateral tumors efficiently, as well as preventing metastasis and postsurgical recurrence, demonstrating great interest for fighting against low-immunogenic breast cancer.
研究领域:
癌症研究
·
纳米技术
·
免疫疗法
·
药物科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Weixia Xu,Xiaofeng Gao,Pengjin Ge,Fuquan Jiang,Xiaokun Zhang,Jingjing Xie
Multidrug resistance (MDR), as a major obstacle in cancer therapy, has resulted in over 90% of cancer chemotherapeutic failure. Mesoporous silica nanospheres (MSNs) have been demonstrated to be tuned with large pore sizes, mediating the MDR-reversal effects. However, the study that surface functionality of the large pore sized-MSNs affects the MDR-overcoming effects hasn’t been extensively studied. In this study, we developed a new dendrimer-like MSNs delivery system based on a rational synthesis strategy and further modified MSNs with various surface functionalities to evaluate their roles in overcoming cancer MDR. Our results showed that the small particle sized-MSNs could be fabricated with dendrimer-like internal structure, resulting in the large pore size of 9 nm. Surface functionality of MSNs, especially hydroxylation and carboxylation, largely improved the intra-nuclear delivery and therapeutic efficiency of DOX for MCF7/ADR cells, which was not up to inhibiting P-gp expression but significantly increasing the intracellular drug accumulation of over 90% even under the strong drug efflux. This study indicates that surface functionality design strategy may display the potential of the large pore sized-MSNs as the efficient chemotherapeutic carriers to combat MDR.
研究领域:
纳米技术
·
药学
·
癌症治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2019
·
IF 0
Xiaomin Zhi,Yuqian Jiang,Linlin Xie,Yanbo Li,Chen-Jie Fang
Multidrug resistance (MDR) and adverse effects of chemotherapeutic agents are severe issues in clinical cancer treatment. Due to the dysregulation of enzymes in the cancer cells, enzyme-responsive drug delivery systems (DDSs) have been considered as a viable technology for cancer chemotherapy. In the present work, doxorubicin (DOX) is visible after leaving from AuNR–LAX. After treatment with AuNR–LAX, the drug resistance index of DOX-resistant MCF-7/ADR cells was reduced from extremely high 955.0 to 1.7, implying high potential of AuNR–LAX in the MDR phenotype cancer treatment. In addition, the cellular viability of both MCF-7 and MCF-7/ADR cells decreased from 50% to 80% after treatment with AuNR–LAX along (equivalent DOX concentration = 2.3 μg/mL, Au concentration = 30 μg/mL) to below 10% after AuNR–LAX treatment plus radiation of 808 nm, due to the NIR photothermal effect of AuNRs. Human bronchial epithelial cell line 16HBE was chosen to evaluate the adverse effect of AuNR–LAX on the normal cells. At the low concentration, the cytotoxicity of LAX and AuNR–LAX is comparable for breast cancer cell MCF-7 and normal cell 16HBE. It is noted that, at high concentration (with equivalent DOX concentration = 13.1 μg/mL, Au concentration = 167.7 μg/mL), the cellular viability of 16HBE cells is over 50%, whereas that of MCF-7 cancer cells is close to 0, implying the potential of AuNR–LAX in reducing the adverse effects of DOX against normal cells/tissues. Overall, AuNR–LAX showed high potential in overcoming MDR and alleviating adverse effect on normal cells.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
ACS Applied Nano Materials
·
2023
·
IF 5.9
Chun-Nan Zhu,Zhi-Jia Wang,Xiang-Peng Li,Si-Yi Chen,Dong-Yun Zheng,Chao Liu,Xiao-Jun Liu,Dong-Bing Cheng,Zeng-Ying Qiao
Multidrug resistance (MDR) is a major factor in chemotherapeutic failure and is closely associated with mitochondrial dysfunction, generating excess adenosine triphosphate (ATP) and overexpressing antiapoptotic protein (Bcl-2). Herein, a site-specific activation of mitochondria-targeting peptide nanotherapeutics is presented for addressing MDR tumor cell selectively, which shows efficient MDR tumor inhibition in vivo. A peptide (KLAKRGD) composed of the mitochondrial cytotoxic peptide (KLAK) and tumor-targeting peptide (RGD) is modified by reactive oxygen species (ROS)-sensitive phenylboronate to yield KLAK (PBAE) RGD, which can self-assemble into nanoparticles and induce mitochondrial cytotoxicity. The KLAK and loaded doxorubicin (DOX) in nanoparticles are selectively activated and released in tumor cells via the overexpression of both the αvβ3 integrin and ROS. ATP and antiapoptotic protein Bcl-2 are reduced as mitochondrial damage accrues, downregulating ATP-dependent drug efflux pumps and drastically enhancing DOX efficacy. The DOX-loaded KLAK (PBAE) RGD (DKPR) nanoparticles improved tumor growth control in drug-resistant tumor models, which suggests the great potential of this innovative approach to targeted chemotherapy in drug-resistant cancers.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Advanced Science
·
2020
·Vol. 7
·期 12
·1902227
·
IF 15.84
Yuan Liu,Yuqian Jia,Kangni Yang,Ruichao Li,Xia Xiao,Kui Zhu,Zhiqiang Wang
Highly persistent incidence of multidrug resistant (MDR) bacterial pathogens constitutes a global burden for public health. An alternative strategy to alleviate such a crisis is to identify promising compounds to restore antibiotics activity against MDR bacteria. It is reported that the antidiabetic drug metformin exhibits the potentiation effect on tetracycline antibiotics, particularly doxycycline and minocycline, against MDR S. aureus , E. faecalis , E. coli , and S. enteritidis . Mechanistic studies demonstrate that metformin promotes intracellular accumulation of doxycycline in tetracycline-resistant E. coli . In addition, metformin boosts the immune response and alleviates the inflammatory responses in vitro. Last, metformin fully restores the activity of doxycycline in three animal infection models. Collectively, these results reveal the potential of metformin as a novel tetracyclines adjuvant to circumvent MDR bacterial pathogens and to improve the treatment outcome of recalcitrant infections.
研究领域:
药理学
·
微生物学
·
传染病学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2018
·
IF 6.383
Fengchun Tian,Fatima Zohra Dahmani,Jianan Qiao,Jiang Ni,Hui Xiong,Tengfei Liu,Jianping Zhou,Jing Yao
Several obstacles are currently impeding the successful treatment of breast cancer, namely impaired drug accumulation into the tumor site, toxicity to normal cells and narrow therapeutic index of chemotherapy, multidrug resistance (MDR) and the metastatic spread of cancer cells through the blood and lymphatic vessels. In this regard, we designed a novel multifunctional nano-sized drug delivery system based on LyP-1 peptide-modified low-molecular-weight heparin-quercetin conjugate (PLQ). This nanosystem was developed for targeted co-delivery of multiple anticancer drugs to p32-overexpressing tumor cells and peritumoral lymphatic vessels, using LyP-1 peptide as active targeting ligand, with the aim to achieve a targeted combinatorial chemo/angiostatic therapy and MDR reversal. The cellular uptake of PLQ nanoparticles by p32-overexpressing breast cancer cells was significantly higher than nonfunctionalized nanoparticles. Besides, the anti-angiogenic activity of PLQ nanoparticles was proven by the effective inhibition of the bFGF-induced neovascularization in subcutaneous Matrigel plugs. More importantly, PLQ/GA nanoparticles with better targeting ability toward p32-positive tumors, displayed a high antitumor outcome by inhibition of tumor cells proliferation and angiogenesis . Immunohistochemistry and western blot assay showed that PLQ/GA nanoparticles significantly disrupted the lymphatic formation of tumor, and inhibited the P-glycoprotein (P-gp) expression in MCF-7 tumor cells, respectively. In conclusion, PLQ/GA nanoparticles provide a synergistic strategy for effective targeted co-delivery of chemotherapeutic and antiangiogenic agents and reversing MDR and metastasis in breast cancer. Statement of Significance Herein, we successfully developed a novel amphiphilic nanomaterial , LyP-1-LMWH-Qu (PLQ) conjugate, consisting of a tumor-targeting moiety LyP-1, a hydrophobic quercetin (a multidrug resistance [MDR]–reversing drug) inner core, and a hydrophilic low-molecular-weight heparin (an antiangiogenic agent) outer shell for encapsulating and delivering a hydrophobic chemotherapeutic agent (gambogic acid). This versatile nanoplatform with multiple targeted features, i.e., dual chemo/angiostatic effects, destruction ability of the peritumoral lymphatic vessels, and reversal of MDR, resulted in a significantly stronger antitumor efficacy and lower toxic side effect than those of nontargeted nanoparticles and the free drug solution. Therefore, this versatile nanosystem might provide a novel insight for the treatment and palliation of breast cancer by targeted co-delivery of chemo/antiangiogenic agents and reversing MDR and metastasis.
研究领域:
肿瘤学
·
药理学
·
纳米技术
·
癌症治疗
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Runan Zuo,Linran Fu,Wanjun Pang,Lingqing Kong,Liangyun Weng,Zeyuan Sun,Ruichao Li,Shaoqi Qu,Lin Li
Antimicrobial resistance (AMR) is a growing public health crisis that requires innovative solutions. Emerging multidrug resistant (MDR) Salmonella typhimurium has raised concern for its effect on pathogenic infection and mortality in humans caused by enteric diseases. To combat these MDR Salmonella typhimurium pathogens, highly effective and broad-spectrum antibiotics such as flufenicol (FFC) need to be evaluated for their potent antibacterial activity against Salmonella typhimurium . However, the low solubility and low oral bioavailability of flufenicol need to be addressed to better combat AMR. In this work, we develop a novel nano-formulation, flufenicol nano-micelles (FTPPM), which are based on D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)/poloxamer 188 (P188), for the targeted treatment of biofilms formed by drug-resistant Salmonella typhimurium in the intestine. Herein, FTPPM were prepared via a thin film hydration method. The preparation process for the mixed micelles is simple and convenient compared with other existing nanodrug delivery systems, which can further decrease production costs. The optimized FTPPM demonstrated outstanding stability and sustained release. An evaluation of the in vivo anti-drug-resistant Salmonella typhimurium efficacy demonstrated that FTPPM showed a stronger efficacy (68.17%) than did florfenicol-loaded TPGS polymer micelles (FTPM), flufenicol active pharmaceutical ingredients (FFC-API), and flufenicol commercially available medicine (FFC-CAM), and also exhibited outstanding biocompatibility. Notably, FTPPM also inhibited drug-resistant Salmonella typhimurium from forming biofilms. More importantly, FTPPM effectively restored intestinal flora disorders induced by drug-resistant Salmonella typhimurium in mice. In summary, FTPPM significantly improved the solubility and oral bioavailability of florfenicol, enhancing its efficacy against drug-resistant Salmonella typhimurium both in vitro and in vivo . FTPPM represent a promising drug-resistant Salmonella typhimurium treatment for curbing bacterial resistance via oral administration.
研究领域:
药学
·
微生物学
·
生物技术
·
药物递送系统
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Xun Guo,Peng Tu,Leilei Zhu,Chen Cheng,Weixi Jiang,Chier Du,Xiaoting Wang,Xiaoling Qiu,Yuanli Luo,Li Wan,Rui Tang,Haitao Ran,Zhigang Wang,Jianli Ren
Cancer multidrug resistance (MDR) is an important reason that results in chemotherapy failure. As a main mechanism of MDR, overexpressed P-glycoprotein (P-gp) utilizes adenosine triphosphate (ATP) to actively pump chemotherapy drugs out of cells. In addition, metabolic reprogramming of drug-resistant tumor cells (DRTCs) exacerbates the specific hypoxic microenvironment and promotes tumor metastasis and recurrence. Therefore, we propose a novel sonodynamic therapy (SDT) paradigm to induce energy metabolism disorder and drug resistance change of DRTCs. A US-controlled “Nanoenabled Energy Metabolism Jammer” (TL@HPN) is designed using perfluoropentane (PFP) adsorbing oxygen in the core, and a targeting peptide (CGNKRTR) is attached to the liposome as the delivery carrier shell to incorporate hematoporphyrin monomethyl ether (HMME) and paclitaxel (PTX). The TL@HPN with ultrasonic/photoacoustic imaging (PAI/USI) precisely controlled the release of drugs and oxygen after being triggered by ultrasound (US), which attenuated the hypoxic microenvironment. SDT boosted the reactive oxygen species (ROS) content in tumor tissues, preferentially inducing mitochondrial apoptosis and maximizing immunogenic cell death (ICD). Persistently elevated oxidative stress levels inhibited ATP production and downregulated P-gp expression by disrupting the redox balance and electron transfer of the respiratory chain. We varied the effect of TL@HPN combined with PD-1/PD-L1 to activate autoimmunity and inhibit tumor metastasis, providing a practical strategy for expanding the use of SDT-mediated tumor energy metabolism.
研究领域:
肿瘤学
·
药理学
·
治疗学
·
免疫学
·
医学影像学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2013
·
IF 5.008
Tianbin Ren,Wei Wu,Menghong Jia,Haiqing Dong,Yongyong Li,Zhouluo Ou
In the treatment of cancer, multidrug resistance (MDR) has been the major obstacle to the success of chemotherapy. The underlying mechanism relies on the overexpression of drug-efflux transporters that prevent the intracellular transport of the drug. In this study, reduction-cleavable vesicles were designed and developed with efficient glutathione-mediated drug-release behavior for reversing drug resistance. Polymeric vesicles were self-assembled from triblock copolymers with disulfide-bond-linked poly(ethylene glycol) (PEG) and poly(ε-benzyloxycarbonyl-l-lysine) (PzLL). Observations from transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM) outline an obvious hollow structure surrounded by a thin outer layer, indicating the successful formation of the vesicles. Using fluorescently detectable doxorubicin hydrochloride (DOX·HCl) as the model drug, a significant acceleration of drug release regulated by glutathione (GSH) was found (>3-fold difference). Upon incubation of the DOX·HCl-loaded polymeric vesicles with the HeLa cervical cancer cell line exposed to glutathione, an enhanced nuclear accumulation of DOX·HCl was observed, elicited by the preferred disassembly of the vesicle structure under reducing conditions. Importantly, by using the gemcitabine hydrochloride (GC·HCl)-resistant breast cancer cell line MDA-MB-231, it was found that cell viability was significantly reduced after treatment with GC·HCl-loaded polymeric vesicles, indicating that these vesicles can help to reverse the drug resistance.
研究领域:
药理学
·
癌症研究
·
聚合物化学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）