A biomimetic nanocomposite with enzyme-like activities and CXCR4 antagonism efficiently enhances the therapeutic efficacy of acute myeloid leukemia

Kong, Fei; He, Hongliang; Bai, Hao; Yang, Fang; Ma, Ming; Gu, Ning; Zhang, Yu

doi:10.1016/j.bioactmat.2022.03.022

Cited by 25 publications

(28 citation statements)

References 35 publications

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“…This is radically different from previously reported nanoparticles or small molecules that were designed as CXCR4 antagonists [ 36 , 37 ]. Thus, their anticancer activity is due to a direct interaction with the receptor, leading to the inhibition of survival and proliferative pathways downstream of CXCR4 that maintain the cancer state.…”

Section: Discussioncontrasting

confidence: 86%

T22-PE24-H6 Nanotoxin Selectively Kills CXCR4-High Expressing AML Patient Cells In Vitro and Potently Blocks Dissemination In Vivo

et al. 2023

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Despite advances in the development of targeted therapies for acute myeloid leukemia (AML), most patients relapse. For that reason, it is still necessary to develop novel therapies that improve treatment effectiveness and overcome drug resistance. We developed T22-PE24-H6, a protein nanoparticle that contains the exotoxin A from the bacterium Pseudomonas aeruginosa and is able to specifically deliver this cytotoxic domain to CXCR4+ leukemic cells. Next, we evaluated the selective delivery and antitumor activity of T22-PE24-H6 in CXCR4+ AML cell lines and BM samples from AML patients. Moreover, we assessed the in vivo antitumor effect of this nanotoxin in a disseminated mouse model generated from CXCR4+ AML cells. T22-PE24-H6 showed a potent, CXCR4-dependent antineoplastic effect in vitro in the MONO-MAC-6 AML cell line. In addition, mice treated with nanotoxins in daily doses reduced the dissemination of CXCR4+ AML cells compared to buffer-treated mice, as shown by the significant decrease in BLI signaling. Furthermore, we did not observe any sign of toxicity or changes in mouse body weight, biochemical parameters, or histopathology in normal tissues. Finally, T22-PE24-H6 exhibited a significant inhibition of cell viability in CXCR4high AML patient samples but showed no activity in CXCR4low samples. These data strongly support the use of T22-PE24-H6 therapy to benefit high-CXCR4-expressing AML patients.

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Section: Discussioncontrasting

confidence: 86%

T22-PE24-H6 Nanotoxin Selectively Kills CXCR4-High Expressing AML Patient Cells In Vitro and Potently Blocks Dissemination In Vivo

et al. 2023

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“…The A549 cell apoptosis was detected using Annexin V-FITC/PI Apoptosis Detection Kit and all experimental steps were almost consistent with the above [ 39 ]. After cell culture, A549 cells were collected using trypsin and washed with PBS three times.…”

Section: Methodssupporting

confidence: 59%

Transmissible H-aggregated NIR-II fluorophore to the tumor cell membrane for enhanced PTT and synergistic therapy of cancer

Wang

Chen

et al. 2023

Nano Convergence

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Photothermal therapy (PTT) combined with second near-infrared (NIR-II) fluorescence imaging (FI) has received increasing attention owing to its capacity for precise diagnosis and real-time monitoring of the therapeutic effects. It is of great clinical value to study organic small molecular fluorophores with both PTT and NIR-II FI functions. In this work, we report a skillfully fluorescent lipid nanosystem, the RR9 (RGDRRRRRRRRRC) peptide-coated anionic liposome loaded with organic NIR-II fluorophore IR-1061 and chemotherapeutic drug carboplatin, which is named RRIALP-C4. According to the structural interaction between IR-1061 and phospholipid bilayer demonstrated by molecular dynamics simulations, IR-1061 is rationally designed to possess the H-aggregated state versus the free state, thus rendering RRIALP-C4 with the activated dual-channel integrated function of intravital NIR-II FI and NIR-I PTT. Functionalization of RRIALP-C4 with RR9 peptide endows the specifically targeting capacity for αvβ3-overexpressed tumor cells and, more importantly, allows IR-1061 to transfer the H-aggregated state from liposomes to the tumor cell membrane through enhanced membrane fusion, thereby maintaining its PTT effect in tumor tissues. In vivo experiments demonstrate that RRIALP-C4 can effectively visualize tumor tissues and systemic blood vessels with a high sign-to-background ratio (SBR) to realize the synergistic treatment of thermochemotherapy by PTT synergistically with temperature-sensitive drug release. Therefore, the strategy of enhanced PTT through H-aggregation of NIR-II fluorophore in the tumor cell membrane has great potential for developing lipid nanosystems with integrated diagnosis and treatment function.

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“…PFOB@PLGA@Pt/GelMA/ODex Nanohybrid Double Network Hydrogel with Multiple Functions Such as Injectability, Tissue Adhesion, Self-Healing, Oxygen-Carrying, and Enzyme-Like Activity. To improve chronic wound hypoxia as well as to provide oxygen as a reaction substrate for polymorphic enzyme activity, we designed A nanocomposite by loading the oxygen-carrying agent perfluorooctyl bromide (PFOB) into PLGA microspheres, 47 followed by coupling amine-modified Pt NPs through the carboxyl groups on the surface of PLGA microspheres. As shown in Figures 2A−C, S2, and S3, aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) images demonstrated the successful synthesis of nanocomposites, which was further evidenced by the change in the hydrodynamic radius (Figure 2D).…”

Section: ■ Introductionmentioning

confidence: 99%

Nanohybrid Double Network Hydrogels Based on a Platinum Nanozyme Composite for Antimicrobial and Diabetic Wound Healing

Zhao

Mei

et al. 2023

ACS Appl. Mater. Interfaces

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Along with hypoxia, severe bacterial infection, and abnormal pH, continuous inflammatory response hinders diabetic wounds from healing. It leads to the accumulation of large amounts of reactive oxygen species (ROS) and therefore prevents the transition of diabetic wounds from the inflammatory phase to the proliferative phase. In this work, a nanohybrid double network hydrogel with injectable, self-healing, and tissue adhesion properties based on a platinum nanozyme composite (PFOB@PLGA@Pt) was constructed to manage diabetic wound healing. PFOB@PLGA@Pt exhibited oxygen supply capacity and enzyme catalytic performance accompanied by pH self-regulation in the entire phases of wound healing. In the first stage, the oxygen carried by perfluorooctyl bromide (PFOB) can ameliorate the hypoxia and boost the glucose oxidase-like catalyzed reaction of Pt NPs, leading to a lowered pH environment with gluconic acid. As a result, the NADH oxidaselike, peroxidase-like, and oxidase-like multiple enzyme activities were activated successively, leading to synergistic antibacterial effects through the production of ROS. After the bacterial infection had cleared, the catalase-like and superoxide dismutase-like activities of Pt NPs reshaped the redox microenvironment by scavenging the excess ROS, which transitioned the wound from the inflammatory phase to the proliferative phase. The microenvironmentally adaptive hydrogel treatment can cover all phases of wound healing, showing the significant promoting effect in the repair of diabetic infected wounds.

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A biomimetic nanocomposite with enzyme-like activities and CXCR4 antagonism efficiently enhances the therapeutic efficacy of acute myeloid leukemia

Cited by 25 publications

References 35 publications

T22-PE24-H6 Nanotoxin Selectively Kills CXCR4-High Expressing AML Patient Cells In Vitro and Potently Blocks Dissemination In Vivo

T22-PE24-H6 Nanotoxin Selectively Kills CXCR4-High Expressing AML Patient Cells In Vitro and Potently Blocks Dissemination In Vivo

Transmissible H-aggregated NIR-II fluorophore to the tumor cell membrane for enhanced PTT and synergistic therapy of cancer

Nanohybrid Double Network Hydrogels Based on a Platinum Nanozyme Composite for Antimicrobial and Diabetic Wound Healing

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