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Chlorin e6
CHEMICAL ENGINEERING JOURNAL · 2023 · IF 15.1

2′-Fluoro-substituted DNA-induced self-assembly strategy for engineering hybrid nanospheres

Haihui Wang,Yifan Jiang,Yichang Liu,Xiaohui Zhu,Yongfei Liu,Minle Chen,Tao Zeng,Zhaowei Chen,Jinyu Li,Chunhua Lu,Huanghao Yang

The physicochemical differences between DNA and other molecules pose a challenge to the construction of DNA-based nanostructures. Herein, we propose a straightforward approach for preparing multifunctional DNA-based nanospheres through direct self-assembly of 2′-fluoro-substituted single-stranded DNA (2′F-DNA) with various small molecules. Molecular dynamics simulation revealed that 2′F substitution in DNA can cause the repulsion of adjacent PO 4 3- group, leading to local stretching of the DNA structure. Moreover, 2′F substituent induced the regular polarization of H 2 O nearby F to form the hydration layer, which interrupts inherent interactions among bases. In this way, the bases of 2′F-DNA chain have fewer constraints and more flexibility in conformation, facilitating their non-covalent interactions with other molecules and enhancing the self-assembly capacity of 2′F-DNA. Consequently, 2′F-DNA can bind to more molecules, tending to spontaneously form hybrid DNA nanospheres. Following this approach, a chemo-gene therapy 2′F-DNA/doxorubicin model was designed, showing the significant synergistic anti-tumor therapeutic efficacy. Taken together, this study provides an expandable approach for constructing engineering hybrid nanospheres using DNA and other small molecules, which holds great potential for further biological applications.

研究领域: 纳米技术 · 生物医学工程 · 分子生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

In situ generation of hybrid alginate hydrogels for enhanced breast tumor ferrotherapy through multiplex magnifying redox imbalances

Huilan Zhuang,Panpan Xue,Sijie Shao,Xuemei Zeng,Shuangqian Yan

Ferroptosis has drawn great attention to tumor treatments over the past decade. However, how to specifically boost tumoral redox imbalance by simultaneously superimposing iron-mediated reactive oxygen species and undermining antioxidative pathways at the tumor site is still a significant challenge in ferroptosis-based tumor ferrotherapy. In this study, we designed an in situ generable hydrogel that contains paclitaxel/chlorin e6-loaded iron-based metal-organic framework (Fe-MOF) nanoparticles for enhanced breast tumor ferrotherapy by multiplex magnifying redox imbalance. The polysaccharide sodium alginate can crosslink with tumoral calcium ions to generate a hydrogel patch, which promotes the retention of Fe-MOF and therapeutic molecules. The Fe-MOF holds peroxidase/glutathione oxidase mimicking properties, resulting in OH generation via the Fenton reaction and glutathione consumption. Local ultrasound treatment facilitates the release of therapeutics and stimulates the generation of signet oxygen by activating the sonosensitizer chlorin e6. In the meanwhile, the low-dose paclitaxel reduces tumoral pH value by downregulating the glutaminolysis-related gene (SLC7A11) which in turn enhances the catalytic activity of Fe-MOF and inhibits antioxidative pathways, respectively. Both in vivo and in vitro experiments show that our designed hybrid hydrogels can induce significant ferrotherapeutic effects by augmenting the tumoral oxidative stresses .

研究领域: 肿瘤学 · 材料科学 · 生物医学工程 · 治疗学
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Theranostics · 2023 · IF 12.4

Light-triggered photosynthetic engineered bacteria for enhanced-photodynamic therapy by relieving tumor hypoxic microenvironment

Chenyang Yin,ZeKun Wang,Chunxue Dai,Bangjia Yang,Weiyun Wang,Endong Yang,Feng Guo,Cundong Fan,Pu Zhang,Jikui Sun,Dongdong Sun

Background: Singlet oxygen ( 1 O 2 ) has received considerable research attention in photodynamic therapy (PDT) due to its cytotoxic solid features. However, the inherent hypoxic state of the tumor microenvironment (TME) leads to the meager 1 O 2 quantum yield of inorganic PDT reagents, and their application in vivo remains elusive. Methods: We developed a novel strategy to fabricate active photosynthetic bacteria/photosensitizer/photothermal agent hybrids for photosynthetic tumor oxygenation and PDT and PTT tumor therapy under different laser irradiation sources. Photosynthetic bacteria combined with Ce6 photosensitizer and Au NPs photothermal agent, the obtained Bac@Au-Ce6 effectively targets tumor tissues and further enhances the tumor accumulation of Au-Ce6. Results: The results showed that the Au-Ce6-loaded engineered bacteria (Bac@Au-Ce6) maintained the photosynthetic properties of Syne . After i.v. injection, Bac@Au-Ce6 efficiently aggregates at tumor sites due to the tumor-targeting ability of active Syne . With 660 nm laser irradiation at the tumor site, the photoautotrophic Syne undergoes sustained photosynthetic O 2 release and immediately activates O 2 to 1 O 2 via a loaded photosensitizer. PTT was subsequently imparted by 808 laser irradiations to enhance tumor killing further. Conclusions: This work provides a new platform for engineering bacteria-mediated photosynthesis to promote PDT combined with PTT multi-faceted anti-tumor.

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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Advanced Healthcare Materials · 2023 ·Vol. 12 ·期 20 ·2300184 · IF 10

Disulfide-Bridged Dendritic Organosilicas-Based Biodegradable Molecularly Imprinted Polymers for Multiple Targeting and pH/Redox-Responsive Drug Release toward Chemical/Photodynamic Synergistic Tumor Therapy

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

In this study, a sialic acid (SA) and transferrin (TF) imprinted biodegradable disulfide bridging organosilicas-based drug delivery system (SS-DMONS/DOX-Ce6@MIPs) for targeted cancer therapy is constructed, for the first time. Disulfide bridged dendritic mesoporous organosilicas nanoparticles (SS-DMONs) not only enhance drug loading as the drug repository, but also provide enough specific surface area for the molecular imprinting shell to expose more degradation and imprinted sites on the surface. In addition,  S  S  can be disturbed in a highly reducing tumor microenvironment to achieve degradation. The biodegradable imprinting film, prepared with customized 2-amino- N -(3,4-dihydroxyphenethyl)-3-mercaptopropanamide and 4-mercaptophenylboronic acid as functional monomers, endows SS-DMONs with active targeting capacity, and responsive drug release through degradation under acidic and highly reductive tumor microenvironment. SS-DMONS/DOX-Ce6@MIPs after binding of TF can target tumor cells actively through multiple interactions, including the affinity between antigen and antibody, and the specific recognition between molecularly imprinted polymers and template molecules. Under laser irradiation the loaded chlorin e6 (Ce6) that can produce toxic reactive oxygen, combined with the doxorubicin (DOX), achieves chemical/photodynamic synergistic anticancer effects. SS-DMONS/DOX-Ce6@MIPs present excellent tumor targeting and dual-responsive drug release, which provides an effective strategy for chemical/photodynamic antitumor therapy.

研究领域: 生物材料学 · 肿瘤学 · 药剂学
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Advanced Healthcare Materials · 2023 · IF 10

Reversing Resistance of Cancer Stem Cells and Enhancing Pdt Based on Hyaluronic Acid Nanomicelles for Preventing Cancer Recurrence and Metastasis

Teng Wang,Jiaojiao Tao,Bingjie Wang,Tianze Jiang,Xia Zhao,Yang Yu,Xin Meng

Photodynamic therapy (PDT) is a promising approach for tumor treatment, however, the therapeutic resistance of cancer stem cells (CSCs) severely limits its efficacy and easily lead to recurrence. Herein, we develop a hyaluronic acid (HA)-Ce6-Olaparib (OLA) micelle (HCCO), which combines the CSC targeting of HA, the PDT effect of Ce6, and the DNA damage repair inhibition of OLA. More importantly, HCCO induces immunogenic cell death (ICD) effects, promotes dendritic cells maturation, and alleviates myeloid-derived suppressor cells (MDSCs) infiltration to reverse CSC resistance. As a result, HCCO not only significantly inhibits the growth of 4T1 breast cancer cells and CSCs in vitro, but also effectively inhibits tumor recurrence and metastasis in vivo. Our study provides a novel strategy for preventing tumor recurrence and metastasis by the combination of inhibiting DNA damage repair, reversing CSC resistance, and enhancing PDT. This article is protected by copyright. All rights reserved

CAS / MDL: 763113-22-0 19660-77-6
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ACS Applied Nano Materials · 2023 · IF 5.9

Antibacterial MoS2-Ce6-Ionic Liquid Nanoplatform against Photothermal/Photodynamic Combined Therapy and Wound Healing Acceleration

Weiwei Zhang,Xiaokuo Shen,Wanzhen Li,Jun Wang,Zhao Kuang,Lin Gui,Yugui Tao,Ping Song,Fei Ge,Longbao Zhu

Drug-resistant bacterial infection is one of the major threats to human health. Multidrug-resistant (MDR) bacteria do not respond satisfactorily to conventional antibiotic treatment. Based on the photothermal effect, molybdenum disulfide (MoS2) nanoparticles, photosensitizer chlorin-e6 (Ce6), and an ionic liquid (IL) were used to construct a multifunctional nanoplatform (MoS2-Ce6-IL), which is responsive to near-infrared light (880 nm) and visible light (660 nm) with combined photothermal and photodynamic bacteriostatic activity. The characterization experiments revealed that the nanoplatform is spherical, with a ζ potential of −14.4 ± 1.1 mV, an overall particle size of about 230 nm, and a photothermal conversion efficiency of 54%. In this study, the treatment regimen was more than 93% effective against MDR Escherichia coli (E. coli) and more than 91% effective against Staphylococcus aureus (S. aureus). It can effectively inhibit MDR bacteria and promote skin wound healing in mice infected with S. aureus. By destroying the bacterial cell membrane and DNA, the nanoplatform interferes with the metabolism of substances and energy in bacterial cells and ultimately causes the death of MDR bacteria. In this study, a multifunctional nanosystem with remarkable bacteriostatic activity was successfully synthesized. The molecular mechanism of multidrug resistance in bacteria was elucidated, laying the foundation for its clinical application.

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