MicroRNA‐Triggered Programmable DNA‐Encoded Pre‐PROTACs for Cell‐Selective and Controlled Protein Degradation DOI

Jiayin Zhan,

Xiang Li, Zhe Chuan Feng

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 9, 2024

Abstract Proteolysis‐targeting chimeras (PROTACs) have accelerated drug development; however, some challenges still exist owing to their lack of tumor selectivity and on‐demand protein degradation. Here, we developed a miR NA‐ i nitiated ssembled pre‐PRO TAC (miRiaTAC) platform that enables the activation termination target degradation in cell type‐specific manner. Using miRNA‐21 as model, engineered DNA hairpins labeled with JQ‐1 pomalidomide facilitated modular assembly DNA‐encoded pre‐PROTACs through hybridization chain reaction. This configuration promoted selective polyubiquitination BRD4 upon miR‐21 initiation, highlighting significant minimal systemic toxicity. Furthermore, incorporates photolabile groups, enabling precise optical control during assembly/disassembly, mitigating risk excessive Additionally, by introducing secondary ligand targeting CDK6, these were used scaffold for programmable active miRiaTACs containing two different warheads exact stoichiometry, orthogonal multitarget The integration near‐infrared light‐mediated photodynamic therapy an upconversion nanosystem further enhanced efficacy potent vivo anticancer activity. We anticipate miRiaTAC represents intersection between dynamic nanotechnology PROTAC, potentially expanding versatility PROTAC toolkit cancer therapy.

Language: Английский

Stimuli-Responsive Polymeric Nanocarriers Accelerate On-Demand Drug Release to Combat Glioblastoma DOI
Muhammad Ismail,

Yibin Wang,

Yundong Li

et al.

Biomacromolecules, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 11, 2024

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with poor prognosis and limited treatment options. Drug delivery by stimuli-responsive nanocarriers holds great promise for improving the modalities of GBM. At beginning review, we highlighted stimuli-active polymeric carrying therapies that potentially boost anti-GBM responses employing endogenous (pH, redox, hypoxia, enzyme) or exogenous stimuli (light, ultrasonic, magnetic, temperature, radiation) as triggers controlled drug release mainly via hydrophobic/hydrophilic transition, degradability, ionizability, etc. Modifying these target ligands further enhanced their capacity to traverse blood-brain barrier (BBB) preferentially accumulate in glioma cells. These unique features lead more effective cancer minimal adverse reactions superior therapeutic outcomes. Finally, review summarizes existing difficulties future prospects treating Overall, this offers theoretical guidelines developing intelligent versatile facilitate precise GBM clinical settings.

Language: Английский

Citations

8
Proteolysis-targeting drug delivery system (ProDDS): integrating targeted protein degradation concepts into formulation design DOI
Yu Chen, Fengyuan Liu,

Samira Pal

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(19), P. 9582 - 9608

Published: Jan. 1, 2024

Targeted protein degradation (TPD) has emerged as a revolutionary paradigm in drug discovery and development, offering promising avenue to tackle challenging therapeutic targets. Unlike traditional approaches that focus on inhibiting function, TPD aims eliminate proteins of interest (POIs) using modular chimeric structures. This is achieved through the utilization proteolysis-targeting chimeras (PROTACs), which redirect POIs E3 ubiquitin ligases, rendering them for by cellular ubiquitin-proteasome system (UPS). Additionally, other technologies such lysosome-targeting (LYTACs) autophagy-based degraders facilitate transportation endo-lysosomal or autophagy-lysosomal pathways degradation, respectively. Despite significant growth preclinical research, many fail progress beyond this stage development. Various factors contribute limited success agents, including hurdle inadequate delivery target site. Integrating into platforms could surmount challenges

Language: Английский

Citations

7
Simplified biomimetic peptide-based vehicle for enhanced tumor penetration and rapid enzyme-induced drug release DOI
Weili Xue,

Xinyue Wei,

Ziyin Xiang

et al.

Journal of Colloid and Interface Science, Journal Year: 2025, Volume and Issue: 684, P. 75 - 86

Published: Jan. 2, 2025

Language: Английский

Citations

1
Universal sulfatase-based chemiluminescence biosensing platform: Validation via AFP detection in clinical blood samples DOI
Cheng Zheng, Mengyuan Cui, Yingyu Zhang

et al.

Biosensors and Bioelectronics, Journal Year: 2024, Volume and Issue: 267, P. 116771 - 116771

Published: Sept. 10, 2024

Language: Английский

Citations

6
Enzymatic control of intermolecular interactions for generating synthetic nanoarchitectures in cellular environment DOI Creative Commons
Weiyi Tan, Qiuxin Zhang,

Mikki Lee

et al.

Science and Technology of Advanced Materials, Journal Year: 2024, Volume and Issue: 25(1)

Published: June 28, 2024

Nanoarchitectonics, as a technology to arrange nano-sized structural units such molecules in desired configuration, requires nano-organization, which usually relies on intermolecular interactions. This review briefly introduces the development of using enzymatic reactions control interactions for generating artificial nanoarchitectures cellular environment. We begin discussion with early examples and uniqueness enzymatically controlled self-assembly. Then, we describe intracellular nanostructures their relevant applications. Subsequently, discuss cases forming cell surface via reactions. Following that, highlight use creating intercellular nanostructures. Finally, provide summary outlook promises future direction this strategy. Our aim is give an updated introduction reaction regulating interactions, phenomenon ubiquitous biology but relatively less explored by chemists materials scientists. goal stimulate new developments simple versatile approach addressing societal needs.

Language: Английский

Citations

3
Spatially Controlled Self‐Assembly of Supramolecular Hydrogels Enabled by Light‐Triggered Catalysis DOI Open Access
Jiahao Zhang, Kai Jin, Yichen Xiao

et al.

Macromolecular Rapid Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Spatial control over supramolecular self-assembly prevails in living system, yet remains difficult to replicate synthetic scenarios. Here, on the basis of a hydrazone formation-mediated hydrogelation access patterning hydrogels is demonstrated via light-triggered catalysis strategy. A photoacid generator that can produce protons aqueous solutions upon irradiation employed. The generated lead drop pH around three units (initial 7.0), effectively accelerating formation and gelators. Because catalysis, samples presence show lower critical gelation concentration, higher stiffness, denser networks. Importantly, by performing selective using differently shaped masks, various spatially resolved following shapes masks are fabricated. concept realize spatial provides an alternative approach toward bottom-up fabrication structured soft materials for applications such as tissue engineering, single cell manipulation, biosensing.

Language: Английский

Citations

0
Aspartate Isomerization Regulates in Situ Assembly of Peptides into Supramolecular Probes for Detection of Protein Carboxyl Methyltransferase in Bladder Cancer DOI
Zeyu Zhang, Xin Liu, Feng Tian

et al.

Nano Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Protein carboxyl methyltransferase (PCMT) restores aspartate isomers in proteins and plays a critical role cancer prognosis. However, vivo detection of PCMT remains challenging. Here, we report the isomerization-regulated situ assembly peptides into supramolecular probes within living cells for bladder cancer. The peptide consists alternating hydrophobic hydrophilic residues contains an isoAsp residue as kinked site to prevent facial amphiphilicity peptide. Exposure converts Asp peptide, thereby promoting its nanofibers. Incorporation 7-nitro-2,1,3-benzoxadiazole (NBD) nanofibers enables based on hydrophobicity-dependent fluorescence NBD units. Both cellular animal studies confirm capability efficient PCMT. Our finding demonstrates strategy regulating systems thus provides new tool creation biomedical agents future.

Language: Английский

Citations

0
Engineering Peptide Self-Assembly: Modulating Noncovalent Interactions for Biomedical Applications DOI Creative Commons
Yaoting Li,

Huanfen Lu,

Liheng Lu

et al.

Accounts of Materials Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 16, 2025

Language: Английский

Citations

0
Noncanonical Amino Acids Dictate Peptide Assembly in Living Cells DOI
Xin Liu, Binbin Hu, Zhilin Yu

et al.

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 19, 2025

ConspectusEmulating the structural features or functions of natural systems has been demonstrated as a state-of-the-art strategy to create artificial functional materials. Inspired by assembly and bioactivity proteins, self-assembly peptides into nanostructures represents promising approach for creating biomaterials. Conventional assembled peptide biomaterials are typically formulated in solution delivered pathological sites implementing theranostic objectives. However, this translocation entails switch from formulation conditions physiological environment raises concerns about material performance. In addition, precise efficient accumulation administered at target remains significant challenge, leading potential biosafety issues associated with off-target effects. These limitations significantly hinder progress advanced To address these concerns, past few years have witnessed development situ living new endeavor optimizing biomaterial performance benefiting advances stimuli-responsive reactions regulating noncovalent interactions. refers processes via sites. Due advantages precisely forming well-defined lesions, situ-formed assemblies integrated interesting next-generation biomedical agents.Despite great developing agents, research area still suffers limited toolkit operating under complicated conditions. Considering amino acids being incorporated backbones modified units, an acid is concern. Therefore, our laboratory intensively engaged designing discovering noncanonical (ncAAs) expand manipulating various biological Thus far, we synthesized containing ncAAs 4-aminoproline, 2-nitroimidazole alanine, Se-methionine, sulfated tyrosine, glycosylated serine, which allow us develop acid-responsive, redox-responsive, enzyme-responsive systems. Based on ncAAs, established complex self-sorting assembly, self-amplified dissipative cells optimize peptides. The resulting exhibit morphological adaptability microenvironment, contributes overcoming delivery barriers improvement targeting accumulation. utilizing developed toolkit, further created supramolecular PROTACs, antagonists, probes cancer treatment diagnosis highlight implications usage. Account, summarize journey emphasis mechanism Eventually, also provide forward conceiving prospects challenges clinical translation situ-formulated

Language: Английский

Citations

0
Advancements in delivery Systems for Proteolysis-Targeting Chimeras (PROTACs): Overcoming challenges and expanding biomedical applications DOI

Yawei Yu,

Weitong Hu,

Yihua Xu

et al.

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: unknown, P. 113719 - 113719

Published: April 1, 2025

Language: Английский

Citations

0