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Small (Weinheim An Der Bergstrasse,... Apr 2024Prostate cancer (PCa) has become a public health concern in elderly men due to an ever-increasing number of estimated cases. Unfortunately, the available treatments are... (Review)
Review
Prostate cancer (PCa) has become a public health concern in elderly men due to an ever-increasing number of estimated cases. Unfortunately, the available treatments are unsatisfactory because of a lack of a durable response, especially in advanced disease states. Extracellular vesicles (EVs) are lipid-bilayer encircled nanoscale vesicles that carry numerous biomolecules (e.g., nucleic acids, proteins, and lipids), mediating the transfer of information. The past decade has witnessed a wide range of EV applications in both diagnostics and therapeutics. First, EV-based non-invasive liquid biopsies provide biomarkers in various clinical scenarios to guide treatment; EVs can facilitate the grading and staging of patients for appropriate treatment selection. Second, EVs play a pivotal role in pathophysiological processes via intercellular communication. Targeting key molecules involved in EV-mediated tumor progression (e.g., proliferation, angiogenesis, metastasis, immune escape, and drug resistance) is a potential approach for curbing PCa. Third, EVs are promising drug carriers. Naïve EVs from various sources and engineered EV-based drug delivery systems have paved the way for the development of new treatment modalities. This review discusses the recent advancements in the application of EV therapies and highlights EV-based functional materials as novel interventions for PCa.
PubMed: 38639331
DOI: 10.1002/smll.202311071 -
Cryo Letters 2024Despite the routine use of cryopreservation for the storage of biological materials, its outcomes are often sub-optimal (including reduced post-thaw viability, recovery,...
Despite the routine use of cryopreservation for the storage of biological materials, its outcomes are often sub-optimal (including reduced post-thaw viability, recovery, and functionality) due to the damage caused by uncontrolled ice growth. Traditional cryoprotective agents (CPAs), including dimethyl sulfoxide (DMSO), fail to prevent damage caused by ice growth and concerns over CPA cytotoxicity have fostered an increased interest in developing improved CPAs and cryoprotection strategies. The inhibition of ice recrystallization by natural antifreeze (glyco)proteins [AF(G)Ps] to improve cryopreservation outcomes has been examined; however, the ice binding properties of these substances and their challenging large-scale production make them poor CPA candidates. Therefore, the development and deployment of biocompatible, small-molecule ice recrystallization inhibitors (IRIs) for use as CPAs is a worthwhile objective. Extensive structure-activity relationship studies on AF(G)Ps revealed that simple carbohydrate derivatives could inhibit ice recrystallization. It was later discovered that this activity could be fine-tuned by delicately balancing the molecule's hydrophobicity and hydrophilicity. Current generation small-molecule IRIs have been meticulously designed to avoid binding to the surface of ice and subsequent biological testing (for both cytotoxicity and cryopreservation efficacy) has demonstrated significant improvements to the cryopreservation outcomes of several cell types. However, an individualized cell-specific approach for the simultaneous assessment of multiple cryopreservation outcomes is necessary to realize the full potential of IRIs as CPAs. This article provides a detailed overview of the development of small-molecule carbohydrate-based IRIs and highlights the crucial cell-specific biological considerations that must be taken into account when assessing cryopreservation outcomes. https://doi.org/10.54680/fr24210110112.
Topics: Cryopreservation; Ice; Cell Survival; Cryoprotective Agents; Carbohydrates; Iris
PubMed: 38557986
DOI: No ID Found -
Analytica Chimica Acta Jun 2024Over the past decades, the proteomics field has undergone rapid growth. Progress in mass spectrometry and bioinformatics, together with separation methods, has brought... (Review)
Review
Over the past decades, the proteomics field has undergone rapid growth. Progress in mass spectrometry and bioinformatics, together with separation methods, has brought many innovative approaches to the study of the molecular biology of the cell. The potential of affinity chromatography was recognized immediately after its first application in proteomics, and since that time, it has become one of the cornerstones of many proteomic protocols. Indeed, this chromatographic technique exploiting the specific binding between two molecules has been employed for numerous purposes, from selective removal of interfering (over)abundant proteins or enrichment of scarce biomarkers in complex biological samples to mapping the post-translational modifications and protein interactions with other proteins, nucleic acids or biologically active small molecules. This review presents a comprehensive survey of this versatile analytical tool in current proteomics. To navigate the reader, the haphazard space of affinity separations is classified according to the experiment's aims and the separated molecule's nature. Different types of available ligands and experimental strategies are discussed in further detail for each of the mentioned procedures.
Topics: Chromatography, Affinity; Proteomics; Humans; Proteins
PubMed: 38692783
DOI: 10.1016/j.aca.2024.342513 -
Small (Weinheim An Der Bergstrasse,... Dec 2023Organic small molecules with processing feasibility, structural diversity, and fine-tuned properties have the potential applications in solar vapor generation. However,...
Organic small molecules with processing feasibility, structural diversity, and fine-tuned properties have the potential applications in solar vapor generation. However, the common defects of narrow solar absorption, low photothermal conversion efficiency, and photobleaching result in limited materials available and unsatisfactory evaporation performance. Herein, the perylene diimide (PDI) derivatives are exploited as stable sunlight absorbers for solar vapor generation. Particularly, the N,N'-bis(3,4,5-trimethoxyphenyl)-3,4,9,10-perylenetetracarboxylic diimide (PDI-DTMA) is well-designed with donor-acceptor-donor configuration based on plane rigid PDI core. The efficient photothermal conversion is enabled through strong intermolecular π-π stacking and intramolecular charge transfer, as revealed by experimental demonstration and theoretical calculation. The PDI-DTMA with a narrow band gap of 1.17 eV exhibits expanded absorption spectrum and enhanced nonradiative transition capability. The 3D hybrid hydrogels (PPHs) combining PDI-DTMA and polyvinyl alcohol are constructed. With the synergistic effect of solar-to-heat conversion, thermal localization management, water activation, and unobstructed water transmission of PPHs, the high water evaporation rates can reach 3.61-10.07 kg m h under one sun. The hydrogels also possess great potential in seawater desalination and sewage treatment. Overall, this work provides valuable insights into the design of photothermal organic small molecules and demonstrates their potentials in solar water evaporation.
PubMed: 37635112
DOI: 10.1002/smll.202305856 -
Small (Weinheim An Der Bergstrasse,... Jan 2024Halloysite nanotubes (HNTs) have emerged as a highly regarded choice in biomedical research due to their exceptional attributes, including superior loading capacity,... (Review)
Review
Halloysite nanotubes (HNTs) have emerged as a highly regarded choice in biomedical research due to their exceptional attributes, including superior loading capacity, customizable surface characteristics, and excellent biocompatibility. HNTs feature tubular structures comprising alumina and silica layers, endowing them with a large surface area and versatile surface chemistries that facilitate selective modifications. Moreover, their substantial pore volume and wide range of pore sizes enable efficient entrapment of diverse functional molecules. This comprehensive review highlights the broad biomedical application spectrum of HNTs, shedding light on their potential as innovative and effective therapeutic agents across various diseases. It emphasizes the necessity of optimizing drug delivery techniques, developing targeted delivery systems, rigorously evaluating biocompatibility and safety through preclinical and clinical investigations, exploring combination therapies, and advancing scientific understanding. With further advancements, HNTs hold the promise to revolutionize the pharmaceutical industry, opening new avenues for the development of transformative treatments.
Topics: Clay; Nanotubes; Drug Delivery Systems
PubMed: 37670217
DOI: 10.1002/smll.202306169 -
Small (Weinheim An Der Bergstrasse,... Oct 2023Extracellular vesicles (EVs) are widely recognized for their potential as drug delivery systems. EVs are membranous nanoparticles shed from cells. Among their natural... (Review)
Review
Extracellular vesicles (EVs) are widely recognized for their potential as drug delivery systems. EVs are membranous nanoparticles shed from cells. Among their natural features are their ability to shield cargo molecules against degradation and enable their functional internalization into target cells. Especially biological or bio-inspired large molecules (LMs), like nucleic acids, proteins, peptides, and others, may profit from encapsulation in EVs for drug delivery purposes. In the last years, a variety of loading protocols are explored for different LMs. The lack of standardization in the EV drug delivery field has impeded their comparability so far. Currently, the first reporting frameworks and workflows for EV drug loading are proposed. The aim of this review is to summarize these evolving standardization approaches and set recently developed methods into context. This will allow for enhanced comparability of future work on EV drug loading with LMs.
Topics: Oligonucleotides; Extracellular Vesicles; Drug Delivery Systems; Pharmaceutical Preparations; Biological Products
PubMed: 37287374
DOI: 10.1002/smll.202301763 -
Talanta May 2024Due to its advantages of label-free and highly sensitive, the resistive pulse sensing with a nanopore has recently become even more potent for the discrimination of...
Due to its advantages of label-free and highly sensitive, the resistive pulse sensing with a nanopore has recently become even more potent for the discrimination of analytes in single molecule level. Generally, a transient interruption of ion current originated from the captured molecule passing through a nanopore will provide the rich information on the structure, charge and translocation dynamics of the analytes. Therefore, nanopore sensors have been widely used in the fields of DNA sequencing, protein recognition, and the portable detection of varied macromolecules and particles. However, the conventional nanopore devices are still lack of sufficient selectivity and sensitivity to distinguish more metabolic molecules involving ATP, glucose, amino acids and small molecular drugs because it is hard to receive a large number of identifiable signals with the fabricated pores comparable in size to small molecules for nanopore sensing. For all this, a series of innovative strategies developed in the past decades have been summarized in this review, including host-guest recognition, engineering alteration of protein channel, the introduction of nucleic acid aptamers and various delivery carriers integrating signal amplification sections based on the biological and solid nanopore platforms, to achieve the high resolution for the small molecules sensing in micro-nano environment. These works have greatly enhanced the powerful sensing capabilities and extended the potential application of nanopore sensors.
PubMed: 38810384
DOI: 10.1016/j.talanta.2024.126323 -
Small (Weinheim An Der Bergstrasse,... Aug 2023In view of the great challenges related to the complexity and heterogeneity of tumors, efficient combination therapy is an ideal strategy for eliminating primary tumors...
In view of the great challenges related to the complexity and heterogeneity of tumors, efficient combination therapy is an ideal strategy for eliminating primary tumors and inhibiting distant tumors. A novel aggregation-induced emission (AIE) phototherapeutic agent called T-TBBTD is developed, which features a donor-acceptor-donor (D-A-D) structure, enhanced twisted molecule conformation, and prolonged second near-infrared window (NIR-II) emission. The multimodal imaging function of the molecule has significance for its treatment time window and excellent photothermal/photodynamic performance for multimode therapy. The precise molecular structure and versatility provide prospects for molecular therapy for anti-tumor applications. Fluorescence imaging in the NIR-II window offers advantages with enhanced spatial resolution, temporal resolution, and penetration depth. The prepared AIE@R837 NPs also have controllable performance for antitumor photo-immunotherapy. Following local photo-irradiation, AIE@R837 NPs generate abundant heat, and O directly kills tumor cells, induces immunogenic cell death (ICD) as a photo-therapeutic effect, and releases R837, which enhances the synergistic effect of antigen presentation and contributes to the long-lasting protective antitumor immunity. A bilateral 4T1 tumor model revealed that this photo-immunotherapy can eliminate primary tumors. More importantly, it has a significant inhibitory effect on distant tumor growth. Therefore, this method can provide a new strategy for tumor therapy.
Topics: Humans; Imiquimod; Neoplasms; Optical Imaging; Immunotherapy; Multimodal Imaging; Nanoparticles; Cell Line, Tumor; Phototherapy
PubMed: 37066745
DOI: 10.1002/smll.202300859 -
Small (Weinheim An Der Bergstrasse,... Jun 2024Activation of small molecules is considered to be a central concern in the theoretical investigation of environment- and energy-related catalytic conversions.... (Review)
Review
Activation of small molecules is considered to be a central concern in the theoretical investigation of environment- and energy-related catalytic conversions. Sub-nanostructured frustrated Lewis pairs (FLPs) have been an emerging research hotspot in recent years due to their advantages in small molecule activation. Although the progress of catalytic applications of FLPs is increasingly reported, the fundamental theories related to the structural formation, site regulation, and catalytic mechanism of FLPs have not yet been fully developed. Given this, it is attempted to demonstrate the underlying theory of FLPs formation, corresponding regulation methods, and its activation mechanism on small molecules using CeO as the representative metal oxide. Specifically, this paper presents three fundamental principles for constructing FLPs on CeO surfaces, and feasible engineering methods for the regulation of FLPs sites are presented. Furthermore, cases where typical small molecules (e.g., hydrogen, carbon dioxide, methane oxygen, etc.) are activated over FLPs are analyzed. Meanwhile, corresponding future challenges for the development of FLPs-centered theory are presented. The insights presented in this paper may contribute to the theories of FLPs, which can potentially provide inspiration for the development of broader environment- and energy-related catalysis involving small molecule activation.
PubMed: 38239093
DOI: 10.1002/smll.202310926 -
Expert Opinion on Drug Discovery Apr 2024Targeting RNAs with small molecules offers an alternative to the conventional protein-targeted drug discovery and can potentially address unmet and emerging medical... (Review)
Review
INTRODUCTION
Targeting RNAs with small molecules offers an alternative to the conventional protein-targeted drug discovery and can potentially address unmet and emerging medical needs. The recent rise of interest in the strategy has already resulted in large amounts of data on disease associated RNAs, as well as on small molecules that bind to such RNAs. Artificial intelligence (AI) approaches, including machine learning and deep learning, present an opportunity to speed up the discovery of RNA-targeted small molecules by improving decision-making efficiency and quality.
AREAS COVERED
The topics described in this review include the recent applications of AI in the identification of RNA targets, RNA structure determination, screening of chemical compound libraries, and hit-to-lead optimization. The impact and limitations of the recent AI applications are discussed, along with an outlook on the possible applications of next-generation AI tools for the discovery of novel RNA-targeted small molecule drugs.
EXPERT OPINION
Key areas for improvement include developing AI tools for understanding RNA dynamics and RNA - small molecule interactions. High-quality and comprehensive data still need to be generated especially on the biological activity of small molecules that target RNAs.
Topics: Humans; Artificial Intelligence; RNA; Drug Discovery; Machine Learning; Small Molecule Libraries
PubMed: 38321848
DOI: 10.1080/17460441.2024.2313455