In Vivo Self-Sorting of Peptides via In Situ Assembly Evolution DOI
Xin Liu, Feng Tian, Zeyu Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(34), P. 24177 - 24187

Published: Aug. 14, 2024

Despite significant progress achieved in artificial self-sorting solution, operating the body remains a considerable challenge. Here, we report an vivo peptide system via situ assembly evolution for combined cancer therapy. The

Language: Английский

Engineering Single-Atom Iron Nanozymes with Radiation-Enhanced Self-Cascade Catalysis and Self-Supplied H2O2 for Radio-enzymatic Therapy DOI
Xianyu Zhu, Jiabin Wu, Ruixue Liu

et al.

ACS Nano, Journal Year: 2022, Volume and Issue: 16(11), P. 18849 - 18862

Published: Oct. 24, 2022

Single-atom nanozymes (SAzymes), with individually isolated metal atom as active sites, have shown tremendous potential enzyme-based drugs for enzymatic therapy. However, using SAzymes in tumor theranostics remains challenging because of deficient activity and insufficient endogenous H2O2. We develop an external-field-enhanced catalysis by atom-level engineered FeN4-centered nanozyme (FeN4-SAzyme) radio-enzymatic This FeN4-SAzyme exhibits peroxidase-like capable catalyzing H2O2 into hydroxyl radicals converting single-site FeII species to FeIII subsequent glutathione oxidase-like activity. Density functional theory calculations are used rationalize the origin self-cascade Importantly, X-rays can improve overall cascade reaction process via promoting conversion frequency FeII/FeIII. As a producer, natural glucose oxidase is further decorated onto surface yield final construct GOD@FeN4-SAzyme. The resulting GOD@FeN4-SAzyme not only supplies situ continuously produce highly toxic but also induces localized deposition radiation dose, subsequently inducing intensive apoptosis ferroptosis vitro. Such synergistic effect radiotherapy therapy allows improved growth inhibition minimal side effects vivo. Collectively, this work demonstrates introduction external fields enhance enzyme-like performance without changing their properties highlights robust therapeutic self-supplying amplifying reactions address limitations treatment.

Language: Английский

Citations

90

Etching Bulk Covalent Organic Frameworks into Nanoparticles of Uniform and Controllable Size by the Molecular Exchange Etching Method for Sonodynamic and Immune Combination Antitumor Therapy DOI
Dianwei Wang, Lin Lin, Tong Li

et al.

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(45)

Published: Aug. 30, 2022

To improve the therapeutic effect of sonodynamic therapy (SDT), more effective and stable sonosensitizers strategies are still required. A covalent organic framework (COF) sonosensitizer is developed by using a new nanoscale COF preparation strategy. This strategy uses molecular etching based on imine exchange reaction to etch bulk into nanoparticles has universal applicability imine-bond-based COF. The regular structure can prevent loss performance caused aggregation porphyrin molecules chemical stability unit. In addition, coordination Fe3+ endows nanoparticle with chemodynamic glutathione consumption ability. combination enhanced SDT α-PD-L1 antibody achieves good antitumor effect. innovative provides avenue for clinical therapy.

Language: Английский

Citations

85

Sulfatase-Induced In Situ Formulation of Antineoplastic Supra-PROTACs DOI

Ninglin Chen,

Zeyu Zhang, Xin Liu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(15), P. 10753 - 10766

Published: April 5, 2024

Proteolysis targeting chimera (PROTAC) technology is an innovative strategy for cancer therapy, which, however, suffers from poor delivery and limited capability protein of interest (POI) degradation. Here, we report a the in situ formulation antineoplastic Supra-PROTACs via intracellular sulfatase-responsive assembly peptides. Coassembling sulfated peptide with two ligands binding to ubiquitin VHL Bcl-xL leads formation pro-Supra-PROTAC, which ratio rationally optimized based on their affinity. The resulting pro-Supra-PROTAC precisely undergoes enzyme-responsive into nanofibrous cells overexpressing sulfatase. Mechanistic studies reveal that pro-Supra-PROTACs selectively cause apparent cytotoxicity through degradation activation caspase-dependent apoptosis, during ligand improves bioactivity POI cell death. In vivo show enhanced tumor accumulation retention pro-Supra-PROTACs, as well inhibiting growth excellent biosafety when coadministrating chemodrugs. Our findings provide new approach enzyme-regulated peptides living development PROTACs high delivering efficiency.

Language: Английский

Citations

20

Deep Penetration of Nanolevel Drugs and Micrometer-Level T Cells Promoted by Nanomotors for Cancer Immunochemotherapy DOI
Huan Chen, Tao Shi, Yue Wang

et al.

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(31), P. 12025 - 12037

Published: July 28, 2021

The ability of nanomotors to promote the deep penetration themselves and loaded drugs in diseased tissues has been proposed confirmed. However, whether such motion behavior can also micrometer-sized immune cells microenvironment, which is important for immunotherapy some diseases, not mentioned. Herein, we construct a nitric oxide (NO)-driven nanomotor that move tumor focusing on its role NO, beneficial product released during movement from this kind nanomotor, regulating infiltration activity cells. It be found drug-loaded with both NO-releasing motility normalization vasculature system degradation intrinsic extracellular matrix (ECM), significantly improve T vivo. efficiency T-cell tissue vivo increased 2.1 28.2%. Both subcutaneous intraperitoneal implantation models validate excellent antitumor effect NO-driven nanomotors. This combination power source their physiological function offers design idea therapeutic agents future many diseases.

Language: Английский

Citations

103

Trident Molecule with Nanobrush–Nanoparticle–Nanofiber Transition Property Spatially Suppresses Tumor Metastasis DOI
Ge Gao, Yao‐Wen Jiang, Wenjun Zhan

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(26), P. 11897 - 11910

Published: June 22, 2022

Metastasis-induced high mortality of cancers urgently demands new approaches to simultaneously inhibit primary tumor metastasis and distant growth. Herein, by rational design a trident molecule Nap-Phe-Phe-Lys(SA-CPT)-Lys(SA-HCQ)-Tyr(H2PO3)-OH (Nap-CPT-HCQ-Yp) with three functional "spears" (i.e., phosphotyrosine motif for enzymatic self-assembly, camptothecin (CPT) chemotherapy, hydroxychloroquine (HCQ) autophagy inhibition) nanobrush-nanoparticle-nanofiber transition property, we propose novel strategy intracellular nanofiber formation synergistic inhibition-enhanced chemotherapy immunotherapy spatial suppression metastasis. Under sequential alkaline phosphatase catalysis carboxylesterase hydrolysis, Nap-CPT-HCQ-Yp undergoes transition, accompanied the releases CPT HCQ. The formed nanofibers effectively invasion behaviors cancer cells. Meanwhile, released HCQ synergistically induce prominent therapeutic effect through chemotherapy. Furthermore, enhances immunogenic cell death, resulting in activation toxic T-cells. Finally, combination checkpoint blockade therapy Nap-CPT-HCQ-Yp-mediated elicits systemic antitumor immunity, thereby achieving efficient inhibitions tumors as well breast model. Our work offers simple feasible "smart" multifunctional prodrugs spatially suppress

Language: Английский

Citations

71

Manipulating Nanoparticle Aggregates Regulates Receptor–Ligand Binding in Macrophages DOI
Yuri Kim, Hee Joon Jung, Yun‐Jung Lee

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(13), P. 5769 - 5783

Published: March 11, 2022

The receptor–ligand interactions in cells are dynamically regulated by modulation of the ligand accessibility. In this study, we utilize size-tunable magnetic nanoparticle aggregates ordered at both nanometer and atomic scales. We flexibly anchor tunable sizes over cell-adhesive RGD (Arg-Gly-Asp)-active material surface while maintaining density dispersed ligands accessible to macrophages constant. Lowering dispersity increasing aggregate size constant facilitates binding integrin receptors ligands, which promotes adhesion macrophages. high dispersity, distant manipulation lift (which increases accessibility) stimulates available under augment macrophage adhesion-mediated pro-healing polarization vitro vivo. low control drop decreases repels away from aggregates, thereby suppressing adhesion, inflammatory polarization. Here, present "accessible dispersity" as a novel fundamental parameter that regulates binding, can be reversibly manipulated decreasing Limitless tuning dimensions morphology offer further insight into regulation host cells.

Language: Английский

Citations

53

Self-Amplifying Assembly of Peptides in Macrophages for Enhanced Inflammatory Treatment DOI
Yanqiu Song, Mingming Li, Na Song

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(15), P. 6907 - 6917

Published: April 7, 2022

Enzyme-regulated in situ self-assembly of peptides represents one versatile strategy the creation theranostic agents, which, however, is limited by strong dependence on enzyme overexpression. Herein, we reported self-amplifying assembly precisely macrophages associated with expression for improving anti-inflammatory efficacy conventional drugs. The assembling system was created via coassembling an enzyme-responsive peptide its derivative functionalized a protein ligand. Reduction NAD(P)H quinone dehydrogenase 1 (NQO1) led to formation nanofibers high affinity protein, thereby facilitating NQO1 expression. improved level conversely promoted into nanofibers, thus establishing amplifying relationship between and macrophages. Utilization as vehicles drug dexamethasone allowed passive targeting delivery acute injured lungs. Both vitro vivo studies confirmed capability enhance simultaneous alleviation reactive oxygen species side effect downregulation proinflammatory cytokines. Our findings demonstrate manipulation living cells regular self-amplification process, providing unique supramolecular agents cells.

Language: Английский

Citations

47

Glutathione‐Induced In Situ Michael Addition between Nanoparticles for Pyroptosis and Immunotherapy DOI
Wenyao Zhen, Yang Liu,

Shangjie An

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(20)

Published: March 20, 2023

Most tumor treatments will fail when ignoring competition and cooperation between each cancer cell its microenvironment. Inspired by game theory, therapeutic agents can be introduced to compete for intracellular molecules disrupt the cells. Biomineralized oxidized (-)-epigallocatechin-3-o-gallate (EGCG)-molybdenum ion coordination nanoparticles were prepared disrupting redox equilibria simultaneously reacting with GSH in a Michael addition form large aggregates that mechanically endosomal plasma membranes, stimulating pyroptosis anti-tumor immunological responses versatile inhibition of different types tumors. This design disrupts immune cells, achieving an optimal payoff therapy.

Language: Английский

Citations

39

A comprehensive review on peptide-bearing biomaterials: From ex situ to in situ self-assembly DOI
Si‐Yong Qin, Jiaqi Feng, Yin‐Jia Cheng

et al.

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 502, P. 215600 - 215600

Published: Dec. 14, 2023

Language: Английский

Citations

38

Tumor‐Specific Peroxynitrite Overproduction Disrupts Metabolic Homeostasis for Sensitizing Melanoma Immunotherapy DOI

Lijun Yang,

Dianyu Wang,

Haixue Jia

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(29)

Published: May 3, 2023

Tumor cells elicit metabolic reprogramming to establish an immunosuppressive tumor microenvironment (TME) for escaping from immunosurveillance. Therefore, interrupting the adaptation of may be a promising strategy TME immunomodulation, favoring immunotherapy. In this work, tumor-specific peroxynitrite nanogenerator APAP-P-NO is constructed that can selectively disrupt homeostasis in melanoma cells. Stimulated by melanoma-characteristic acid, glutathione, and tyrosinase, efficiently generate through situ coupling produced superoxide anion released nitric oxide. Metabolomics profiling reveals accumulated induces great decrease metabolites tricarboxylic acid cycle. Meanwhile, glycolysis-produced lactate drops sharply both intracellularly extracellularly under stress. Mechanistically, impairs activity glyceraldehyde-3-phosphate dehydrogenase glucose metabolism S-nitrosylation. The alterations effectively reverse evoke potent antitumor immune responses, including polarization M2-like macrophages M1phenotype, reduction myeloid-derived suppressor regulatory T cells, restoration CD8+ cell infiltration. Combining with anti-PD-L1 achieves significant inhibition against primary metastatic melanomas without systemic toxicities. Collectively, overproduction approach developed possible mechanism peroxynitrite-mediated immunomodulation explored, providing new facilitating immunotherapy sensitivity.

Language: Английский

Citations

37