ACS Applied Nano Materials
·
2024
·
IF 5.3
Hui Zhang,Xuelin You,Ruihan Liu,You Wang,Fang Han,Juanyuan Hao,Yu Li
Cuproptosis efficiency is severely limited by insufficient Cu+ contents in tumors due to the easy oxidation of Cu+ into Cu2+ and the copper efflux mechanism. Herein, we develop a copper nanocarrier (MoSe2/CuO2) that can significantly enhance intracellular Cu+ for self-boosting cuproptosis-based synergistic antitumor therapy. Upon endocytosis by cancer cells, the acidic tumor microenvironment (TME) triggers the degradation of MoSe2/CuO2 to release Cu2+. MoSe2 then acts as a cocatalyst that promotes the reduction of released Cu2+ to Cu+, while oxidizing active Mo4+ to Mo6+, thereby triggering cuproptosis. Importantly, the produced Mo6+ is further returned to Mo4+ by endogenous glutathione (GSH) depletion, enhancing the cocatalytic effects of MoSe2 and resulting in a continuous Cu+ generation for self-boosting cuproptosis. Meanwhile, GSH-enhanced cocatalysis and MoSe2-mediated photothermal effect can significantly promote Cu-Fenton reactions, which not only downregulate Cu-ATPase to reduce Cu+ efflux and aggravate cuproptosis with higher efficacy but also activate caspase-3 to promote cell apoptosis. MoSe2/CuO2 exhibits excellent antitumor effects (94.9% tumor growth inhibition) and biosafety effects in vitro and in vivo. This work presents a strategy that enables high levels of Cu+ delivery by enhancing generation and reducing efflux for self-boosting cuproptosis–apoptosis synergistic therapy.
研究领域:
纳米技术
·
癌症研究
·
生物医学工程
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Junqin Li,Mengya Sun,Xiaoxian Tang,Yuqian Liu,Chunlei Ou,Yuze Luo,Li Wang,Luo Hai,Le Deng,Dinggeng He
Reactive oxygen species (ROS) are widely considered to the effective therapeutics for fighting bacterial infections especially those associated with biofilm. However, biofilm microenvironments including hypoxia, limited H 2 O 2 , and high glutathione (GSH) level seriously limit the therapeutic efficacy of ROS-based strategies. Herein, we have developed an acidic biofilm microenvironment-responsive antibacterial nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO 2 ) synthesized in situ and indocyanine green (ICG). The three-in-one nanotherapeutics (CuO 2 /ICG@CBSA) are capable of releasing Cu 2+ and H 2 O 2 in a slightly acidic environment, where Cu 2+ catalyzes the conversion of H 2 O 2 into hydroxyl radical (•OH) and consumes the highly expressed GSH to disrupt the redox homeostasis. With the assistance of an 808 nm laser, the loaded ICG not only triggers the production of singlet oxygen ( 1 O 2 ) by a photodynamic process, but also provides photonic hyperpyrexia that further promotes the Fenton-like reaction for enhancing •OH production and induces thermal decomposition of CuO 2 for the O 2 -self-supplying 1 O 2 generation. The CuO 2 /ICG@CBSA with laser irradiation demonstrates photothermal-augmented multi-mode synergistic bactericidal effect and is capable of inhibiting biofilm formation and eradicating the biofilm bacteria. Further in vivo experiments suggest that the CuO 2 /ICG@CBSA can effectively eliminate wound infections and accelerate wound healing. The proposed three-in-one nanotherapeutics with O 2 /H 2 O 2 -self-supplied ROS generating capability show great potential in treating biofilm-associated bacterial infections. Statement of Significance Here, we have developed an acidic biofilm microenvironment-responsive nanoplatform consisting of copper-dopped bovine serum albumin (CBSA) loaded with copper peroxide (CuO 2 ) synthesized in situ and indocyanine green (ICG). The nanotherapeutics (CuO 2 /ICG@CBSA) are capable of releasing Cu 2+ and H 2 O 2 in an acidic environment, where Cu 2+ catalyzes the conversion of H 2 O 2 into •OH and consumes the overexpressed GSH to improve oxidative stress. With the aid of an 808 nm laser, ICG provides photonic hyperpyrexia for enhancing •OH production, and triggers O 2 -self-supplying 1 O 2 generation. CuO 2 /ICG@CBSA with laser irradiation displays photothermal-augmented multi-mode antibacterial and antibiofilm effect. Further in vivo experiments prove that CuO 2 /ICG@CBSA effectively eliminates wound infection and accelerates wound healing. The proposed three-in-one nanotherapeutics show great potential in treating biofilm-associated bacterial infections.
研究领域:
纳米技术
·
生物材料
·
生物医学工程
·
微生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Manman Liang,Limin Shang,Yixin Yu,Yujie Jiang,Qiang Bai,Junchi Ma,Dongqin Yang,Ning Sui,Zhiling Zhu
Chemodynamic therapy (CDT) employs Fenton catalysts to kill bacteria by converting hydrogen peroxide (H 2 O 2 ) into toxic hydroxyl radical (•OH). Among them, Fenton-type metal peroxide nanoparticles fascinate nanomaterials with intriguing physiochemical properties, but research on this antibacterial agent is still in its infancy. Herein, a distinct CuO 2 /TiO 2 heterostructure constituted of ultrasmall copper peroxide (CuO 2 ) nanoclusters and sonosensitized ultrathin oxygen vacancy-rich porous titanium oxide (OV-TiO 2 ) nanosheets was developed and was incorporated into microneedles for bilaterally augmented sono-chemodynamic and sonothermal antibacterial therapy. Engineering CuO 2 nanoclusters on the surface of TiO 2 nanosheets not only endows the Fenton catalytic activity for sono-chemodynamic therapy (SCDT), but also improves the sonodynamic and sonothermal performance of TiO 2 by narrowing the bandgap of TiO 2 and suppressing the recombination of electron–hole pairs. The high efficacy of this CuO 2 /TiO 2 integrated microneedle (CTMN) patch was systematically demonstrated both in vitro and in vivo with the eliminating rate >99.9999% against multidrug resistant (MDR) pathogens in 5 min as well as accelerated wound tissue healing. This work highlights a promisingly new and efficient strategy for the development of sonosensitive and chemoreactive nanomedicine for non-antibiotic therapies. Statement of significance Feton-type metal peroxides, a novel nanomaterial with self-supplied oxygen and hydrogen peroxide, can achieve effective antimicrobial activity in vitro. However, there is a lack of effective nanomaterial delivery systems and suitable means for in vivo activation/enhancement of antimicrobial activity during bacterial infected skin wound treatment. In this study, we designed and prepared efficient ultrasound activable microneedles that effectively addressed the deficiencies mentioned above and established a new paradigm for efficient utilization of metal peroxide nanomaterials and ultrasound based strategies. Noticeably, copper peroxide nanoclusters/oxygen vacancy-rich porous titanium oxide nanosheets (CuO 2 /TiO 2 ) integrated microneedle (CTMN) patch combines advantages of both sono-chemodynamic and sonothermal antibacterial therapy, achieving one of the most instant and effective antibacterial efficacy (>99.9999% in 5 min) in vivo reported till now.
研究领域:
纳米医学
·
抗菌治疗
·
材料科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Guoting Su,Hui Xu,FangFang Zhou,Xiyu Gong,Songwen Tan,Yongju He
Generating lethal reactive oxygen species (ROS) within tumors by nanocatalytic medicines is an advanced strategy for tumor-specific therapy in recent years. Nevertheless, the low yield of ROS restrains its therapeutic efficiency. Herein, a dual-catalytic nanomedicine based on tumor microenvironment (TME)-responsive liposomal nanosystem co-delivering CuO2 and dihydroartemisinin (DHA) (LIPSe@CuO2&DHA) is developed to boost ROS generation against tumor. The liposomal nanosystem can degrade in the ROS-overexpressed TME and liberate CuO2 and DHA to initiate Cu-based dual-catalytic ROS generation. Serving as generators of H2O2 and Cu2+, CuO2 can self-produce plenty of toxic hydroxyl radicals via Fenton-like reaction in the acidic TME. Meanwhile, the released Cu2+ can catalyze DHA to generate cytotoxic C-centered radicals. Together, the self-supplied H2O2 and Cu-based dual-catalytic reaction greatly increase the intratumoral level of lethal ROS. Importantly, Cu2+ can decrease the GSH-mediated scavenging effect on the produced ROS via a redox reaction and undergo a Cu2+-to-Cu+ conversion to enhance the Fenton-like reaction, further guaranteeing the high efficiency of ROS generation. Resultantly, LIPSe@CuO2&DHA induces remarkable cancer cell death and tumor growth inhibition, which may present a promising nanocatalytic medicine for cancer therapy.
研究领域:
纳米医学
·
癌症治疗
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DALTON TRANSACTIONS
·
2022
·Vol. 51
·期 30
·11325-11334
·
IF 4.569
Yale Hong,Qinfeng Tao,Yuan-Yuan Liu,Zhuo Wang,Haifang Wang,Lining Sun
Chemodynamic therapy (CDT) can convert endogenous hydrogen peroxide (H2O2) to highly reactive hydroxyl radical (˙OH) through Fenton or Fenton-like reaction to kill tumor cells, which is a promising anticancer strategy. However, the limited H2O2 and overexpressed glutathione (GSH) in tumor cells make CDT ineffective. Here, an efficient nanocomposite, UCN@CuO2–GOx (UCCuG), was synthesized, realizing both starvation therapy and H2O2 self-supplying CDT in vitro. In this case, the glucose oxidase (GOx) of the nanocomposite could consume glucose for starvation therapy after the UCCuG nanocomposite entered tumor cells. In addition, the acidic environment of the lysosome triggered the release of Cu2+ and H2O2 by the decomposition of UCCu; then, Cu2+ was reduced to Cu+ by GSH in tumor cells; and finally, Cu+ catalyzed the released H2O2 to generate ˙OH for CDT. The in vitro experiments demonstrated starvation-enhanced CDT with remarkable results. Meanwhile, under 980 nm laser irradiation, the upconversion luminescence signal of UCN in the UCCuG nanocomposite was reduced due to the CuO2–GOx coating, while it gradually recovered after the UCCuG nanocomposite reacted with glucose and GSH under the tumor microenvironment (TME). Such a luminescent intensity recovery process is expected to monitor the TME-activated therapeutic effect in real time. This strategy may solve the problem of insufficient CDT efficacy caused by limited endogenous H2O2 and overexpressed GSH in tumor cells. This multifunctional nanocomposite demonstrates the promising application of starvation-enhanced CDT in tumor treatment.
研究领域:
纳米技术
·
癌症治疗
·
生物医学工程
·
化学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Fiber Materials
·
2024
·
IF 17.2
Qi Lin,Huang Yong,Liu Zheng,Liu Jiangshan,Wang Jing,Xu Huilun,Yang Hao,Liu Limin,Feng Ganjun,Zhang Shuyu,Li Yubao,Zhang Li
Delayed healing of diabetic wounds poses a major challenge to human health due to severe vascular dysfunction, sustained inflammation, and vulnerability to microbial infection. Herein, we constructed multidimensionally nano-topologized electrospun polycaprolactone (PCL) fibrous membranes with shish-kebab nanoarrays on each fiber through self-induced crystallization, on which the CuO 2 –MgO 2 bimetallic peroxide nanodots (BPNs) were anchored by polydopamine (PDA) as the bridging layer. When activated by the acidic microenvironment (typically infected diabetic wound), BPNs on fibers reacted immediately to release Cu 2+ and Mg 2+ ions together with hydrogen peroxide (H 2 O 2 ) molecules, which were then transferred into ·OH radicals through Fenton-type reactions catalyzed by Cu 2+ for instant bacteria elimination. At the same time, the released Cu 2+ and Mg 2+ ions were retained to improve the angiogenesis and suppress the inflammation infiltration, thus remodeling the wound microenvironment. Meanwhile, the one-dimensional (1D)-constructed nano shish-kebabs and PDA coating on fibers provided additional topological activation for cell adhesion and directed migration along the aligned fiber orientation. Through the meticulous design, the resultant membranes markedly accelerated the infected wound healing in the diabetic rat model. This study pioneers a unique design to develop a nanocomposite fibrous membrane that combines multidimensional topologies with chemodynamic therapy (CDT), for efficiently combating infected diabetic wounds. Graphical abstract
研究领域:
材料科学
·
生物医学工程
·
纳米技术
·
伤口愈合
·
组织工程
·
药物递送系统
·
生物材料
✓ 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）