Cellular Uptake of Cell‐Penetrating Peptides Activated by Amphiphilic p‐Sulfonatocalix[4]arenes DOI Creative Commons
Chusen Huang,

Yan‐Cen Liu,

Hyeyoung Oh

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(28)

Published: March 8, 2024

We report the synthesis of a series amphiphilic p-sulfonatocalix[4]arenes with varying alkyl chain lengths (CX4-Cn) and their application as efficient counterion activators for membrane transport cell-penetrating peptides (CPPs). The enhanced activity is confirmed carboxyfluorescein (CF) assay in vesicles by direct cytosolic delivery CPPs into CHO-K1, HCT 116, KTC-1 cells enabling excellent cellular uptake two cancer cell lines. Intracellular was fluorescence microscopy after CPP entry live mediated CX4-Cn, which also quantified lysis spectroscopy. results present first systematic exploration structure-activity relationships calixarene-based show that CX4-Cn are exceptionally effective CPPs. dodecyl derivative, CX4-C12, serves best activator. A mechanistic insight provided at 4 °C presence endocytosis inhibitor dynasore, indicates translocation CPP-counterion complexes cytosol highlights potential benefits CPP-conjugated cargo molecules cells.

Language: Английский

Virtual Screening of Peptide Libraries: The Search for Peptide-Based Therapeutics Using Computational Tools DOI Open Access
Marian Vincenzi, Flavia Anna Mercurio, Marilisa Leone

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1798 - 1798

Published: Feb. 1, 2024

Over the last few decades, we have witnessed growing interest from both academic and industrial laboratories in peptides as possible therapeutics. Bioactive a high potential to treat various diseases with specificity biological safety. Compared small molecules, represent better candidates inhibitors (or general modulators) of key protein–protein interactions. In fact, undruggable proteins containing large smooth surfaces can be more easily targeted conformational plasticity peptides. The discovery bioactive peptides, working against disease-relevant protein targets, generally requires high-throughput screening libraries, silico approaches are highly exploited for their low-cost incidence efficiency. present review reports on challenges linked employment therapeutics describes computational approaches, mainly structure-based virtual (SBVS), support identification novel therapeutic implementations. Cutting-edge SBVS strategies reviewed along examples applications focused diverse classes (i.e., anticancer, antimicrobial/antiviral blocking amyloid fiber formation).

Language: Английский

Citations

15
Anti-stromal nanotherapeutics for hepatocellular carcinoma DOI
Zhuo Yu, Leaf Huang, Jianfeng Guo

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 367, P. 500 - 514

Published: Feb. 3, 2024

Language: Английский

Citations

11
Peptide‐Functionalized Inorganic Oxide Nanomaterials for Solid Cancer Imaging and Therapy DOI

Xiaolin Duan,

Pin Wang,

Lulu He

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(37)

Published: Feb. 9, 2024

Abstract The diagnosis and treatment of solid tumors have undergone significant advancements marked by a trend toward increased specificity integration imaging therapeutic functions. multifaceted nature inorganic oxide nanomaterials (IONs), which boast optical, magnetic, ultrasonic, biochemical modulatory properties, makes them ideal building blocks for developing multifunctional nanoplatforms. A promising class materials that emerged in this context are peptide‐functionalized (PFIONs), demonstrated excellent performance therapy, making potential candidates advancing tumor treatment. Owing to the functionalities peptides targeting, penetration, responsiveness, well‐designed PFIONs can specifically accumulate release or agents at sites, enabling precise effective This review provides an overview recent advances use tumors, highlighting superiority as well synergistic Moreover, discusses challenges prospects depth, aiming promote intersection interdisciplinary facilitate their clinical translation development personalized diagnostic systems optimizing material systems.

Language: Английский

Citations

11
Efficient Delivery of Oncolytic Peptide LTX-315 by ZIF-8: pH-Responsive Release, Improved Stability, and Reduced Hemolysis DOI

Xin‐Qi Chen,

Sheng Cui, Yuzhen Chen

et al.

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

The first-in-class oncolytic peptide LTX-315 has exhibited positive anticancer responses in multiple phase I/II clinical trials. Nevertheless, the linear suffers from poor proteolytic stability and undesired toxicity, especially hemolysis, which may limit its widespread applications. Except for direct structural modifications, drug delivery systems (DDSs) are expected to protect degradation shield hemolytic properties. Therefore, zeolitic imidazolate framework (ZIF-8)-based nanoparticles (NPs) were constructed with a high encapsulation rate of 59.9%, utilizing biomineralized "one-pot method" an aqueous system. release LTX-315, vitro potency, serum stability, durability, antimigration activity, hemolysis effect, subcellular localization, membrane disruption/permeation effects LTX-315@ZIF-8 NPs investigated. potent cytotoxicity against cancer cells. experiment time-inhibition curve assay indicated that ZIF-8 could effectively improve prolong duration action, enhance cytostatic potency. Especially, not only attenuated toxicity but also achieved pH-responsive LTX-315. mechanism investigation possessed membranolytic activity reduced mitochondrial potential trigger cell death. Collectively, this paper established robust strategy reduce properties provided reliable reference future peptides.

Language: Английский

Citations

1
Development of D-melittin polymeric nanoparticles for anti-cancer treatment DOI
Shixian Lv, Meilyn Sylvestre, Kefan Song

et al.

Biomaterials, Journal Year: 2021, Volume and Issue: 277, P. 121076 - 121076

Published: Aug. 23, 2021

Language: Английский

Citations

53
Polymeric Nanomaterials for Efficient Delivery of Antimicrobial Agents DOI Creative Commons
Yin Wang, Hui Sun

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(12), P. 2108 - 2108

Published: Dec. 7, 2021

Bacterial infections have threatened the lives of human beings for thousands years either as major diseases or complications. The elimination bacterial has always occupied a pivotal position in our history. For long period time, people were devoted to finding natural antimicrobial agents such peptides (AMPs), antibiotics and silver ions synthetic active substances including peptoids, metal oxides polymers combat infections. However, with emergence multidrug resistance (MDR), infection become one most urgent problems worldwide. efficient delivery site precisely is promising strategy reducing resistance. Polymeric nanomaterials been widely studied carriers constructing agent systems shown advantages high biocompatibility, sustained release, targeting improved bioavailability. In this review, we will highlight recent advances highly by polymeric micelles, vesicles, dendrimers, nanogels, nanofibers so forth. biomedical applications nanomaterial-based combating MDR bacteria, anti-biofilms, wound healing, tissue engineering anticancer are demonstrated. Moreover, conclusions future perspectives also proposed.

Language: Английский

Citations

45
Properties and Bioapplications of Amphiphilic Janus Dendrimers: A Review DOI Creative Commons
Adina Căta, Ioana Maria Carmen Ienașcu,

Mariana Nela Ştefănuț

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(2), P. 589 - 589

Published: Feb. 9, 2023

Amphiphilic Janus dendrimers are arrangements containing both hydrophilic and hydrophobic units, capable of forming ordered aggregates by intermolecular noncovalent interactions between the dendrimer units. Compared to conventional dendrimers, these molecular self-assemblies possess particular effective attributes i.e., presence different terminal groups, essential design new elaborated materials. The present review will focus on pharmaceutical biomedical application amphiphilic dendrimers. Important information for development novel optimized formulations, such as structural classification, synthetic pathways, properties applications, offer complete characterization this type This work constitute an up-to-date background specialists involved in designing dendrimer-based nanomaterials future innovations promising field.

Language: Английский

Citations

21
Persistent Degradation of HER2 Protein by Hybrid nanoPROTAC for Programmed Cell Death DOI

Zhihang Wang,

Mixiao Tan, Wen Su

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(9), P. 6263 - 6273

Published: April 24, 2023

Proteolysis-targeting chimera (PROTAC) has emerged as a promising strategy for degrading proteins of interest. Peptide-based PROTACs offer several advantages over small-molecule-based PROTACs, such high specificity, low toxicity, and large protein–protein interaction surfaces. However, peptide-based have intrinsic shortcomings that strongly limit their application including poor cell permeability stability potency. Herein, we designed nanosized hybrid PROTAC (GNCTACs) to target degrade human epidermal growth factor receptor 2 (HER2) in tumor cells. Gold nanoclusters (GNCs) were utilized connect HER2-targeting peptides cereblon (CRBN)-targeting ligands. GNCTACs could overcome the barriers efficiently delivering cytoplasm protecting them from degradation. Furthermore, fasting-mimicking diet was applied enhance cellular uptake proteasome activity. Consequently, more than 95% HER2 SKBR3 cells degraded by GNCTACs, degradation lasted at least 72 h, showing catalytic-like reaction.

Language: Английский

Citations

20
The power of super-resolution microscopy in modern biomedical science DOI
Nan Sun, Yi Jia, Shiwei Bai

et al.

Advances in Colloid and Interface Science, Journal Year: 2023, Volume and Issue: 314, P. 102880 - 102880

Published: March 13, 2023

Language: Английский

Citations

15
Imaging of Escherichia coli K5 and glycosaminoglycan precursors via targeted metabolic labeling of capsular polysaccharides in bacteria DOI Creative Commons

Yu-Jia Wang,

Lian Li, Jie Yu

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(7)

Published: Feb. 17, 2023

The introduction of unnatural chemical moieties into glycosaminoglycans (GAGs) has enormous potential to facilitate studies the mechanism and application these critical, widespread molecules. Unnatural N-acetylhexosamine analogs were metabolically incorporated capsule polysaccharides Escherichia coli Bacillus subtilis via bacterial metabolism. Targeted metabolic labeled hyaluronan precursors heparin chondroitin sulfate obtained. azido-labeled (purified or in capsules) reacted with dyes, bioorthogonal chemistry, enable detection imaging. Site-specific fluorophores directly onto cell surfaces affords another choice for observing quantifying bacteria vivo vitro. Furthermore, azido-polysaccharides retain similar biological properties their natural analogs, reliable predictable functionalities, such as fluorophores, azido-N-hexosamines disaccharide repeat units provides tools imaging analysis GAGs

Language: Английский

Citations

14