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1.
Nano Today ; 562024 Jun.
Article in English | MEDLINE | ID: mdl-38854931

ABSTRACT

Nanotherapeutics have gained significant attention for the treatment of numerous cancers, primarily because they can accumulate in and/or selectively target tumors leading to improved pharmacodynamics of encapsulated drugs. The flexibility to engineer the nanotherapeutic characteristics including size, morphology, drug release profiles, and surface properties make nanotherapeutics a unique platform for cancer drug formulation. Polymeric nanotherapeutics including micelles and dendrimers represent a large number of formulation strategies developed over the last decade. However, compared to liposomes and lipid-based nanotherapeutics, polymeric nanotherapeutics have had limited clinical translation from the laboratory. One of the key limitations of polymeric nanotherapeutics formulations for clinical translation has been the reproducibility in preparing consistent and homogeneous large-scale batches. In this review, we describe polymeric nanotherapeutics and discuss the most common laboratory and scale-up formulation methods, specifically those proposed for clinical cancer therapies. We also provide an overview of the major challenges and opportunities for scaling polymeric nanotherapeutics to clinical-grade formulations. Finally, we will review the regulatory requirements and challenges in advancing nanotherapeutics to the clinic.

2.
Nanotechnology ; 35(37)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38853586

ABSTRACT

A new type of 0-dimensional carbon-based materials called graphene quantum dots (GQDs) is gaining significant attention as a non-toxic and eco-friendly nanomaterial. GQDs are nanomaterials composed of sp2hybridized carbon domains and functional groups, with their lateral size less than 10 nm. The unique and exceptional physical, chemical, and optical properties arising from the combination of graphene structure and quantum confinement effect due to their nano-size make GQDs more intriguing than other nanomaterials. Particularly, the low toxicity and high solubility derived from the carbon core and abundant edge functional groups offer significant advantages for the application of GQDs in the biomedical field. In this review, we summarize various synthetic methods for preparing GQDs and important factors influencing the physical, chemical, optical, and biological properties of GQDs. Furthermore, the recent application of GQDs in the biomedical field, including biosensor, bioimaging, drug delivery, and therapeutics are discussed. Through this, we provide a brief insight on the tremendous potential of GQDs in biomedical applications and the challenges that need to be overcome in the future.


Subject(s)
Biosensing Techniques , Graphite , Quantum Dots , Graphite/chemistry , Quantum Dots/chemistry , Humans , Biosensing Techniques/methods , Drug Delivery Systems , Animals
3.
ACS Biomater Sci Eng ; 10(7): 4227-4236, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38848308

ABSTRACT

Anticancer drugs are often associated with limitations such as poor stability in aqueous solutions, limited cell membrane permeability, nonspecific targeting, and irregular drug release when taken orally. One possible solution to these problems is the use of nanocarriers of drug molecules, particularly those with targeting ability, stimuli-responsive properties, and high drug loading capacity. These nanocarriers can improve drug stability, increase cellular uptake, allow specific targeting of cancer cells, and provide controlled drug release. While improving the therapeutic efficacy of cancer drugs, contemporary researchers also aim to reduce their associated side effects, such that cancer patients are offered with a more effective and targeted treatment strategy. Herein, a set of nine porous covalent organic frameworks (COFs) were tested as drug delivery nanocarriers. Among these, paclitaxel loaded in COF-3 was most effective against the proliferation of ovarian cancer cells. This study highlights the emerging potential of COFs in the field of therapeutic drug delivery. Due to their biocompatibility, these porous COFs provide a viable substrate for controlled drug release, making them attractive candidates for improving drug delivery systems. This work also demonstrates the potential of COFs as efficient drug delivery agents, thereby opening up new opportunities in the field of sarcoma therapy.


Subject(s)
Antineoplastic Agents , Drug Carriers , Metal-Organic Frameworks , Ovarian Neoplasms , Paclitaxel , Humans , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Drug Carriers/chemistry , Female , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Paclitaxel/therapeutic use , Paclitaxel/chemistry , Paclitaxel/pharmacology , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/therapeutic use , Metal-Organic Frameworks/pharmacology , Cell Line, Tumor , Porosity , Drug Liberation
4.
J Control Release ; 372: 619-647, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38909702

ABSTRACT

In recent years, enzyme therapy strategies have rapidly evolved to catalyze essential biochemical reactions with therapeutic potential. These approaches hold particular promise in addressing rare genetic disorders, cancer treatment, neurodegenerative conditions, wound healing, inflammation management, and infectious disease control, among others. There are several primary reasons for the utilization of enzymes as therapeutics: their substrate specificity, their biological compatibility, and their ability to generate a high number of product molecules per enzyme unit. These features have encouraged their application in enzyme replacement therapy where the enzyme serves as the therapeutic agent to rectify abnormal metabolic and physiological processes, enzyme prodrug therapy where the enzyme initiates a clinical effect by activating prodrugs, and enzyme dynamic or starving therapy where the enzyme acts upon host substrate molecules. Currently, there are >20 commercialized products based on therapeutic enzymes, but approval rates are considerably lower than other biologicals. This has stimulated nanobiotechnology in the last years to develop nanoparticle-based solutions that integrate therapeutic enzymes. This approach aims to enhance stability, prevent rapid clearance, reduce immunogenicity, and even enable spatio-temporal activation of the therapeutic catalyst. This comprehensive review delves into emerging trends in the application of therapeutic enzymes, with a particular emphasis on the synergistic opportunities presented by incorporating enzymes into nanomaterials. Such integration holds the promise of enhancing existing therapies or even paving the way for innovative nanotherapeutic approaches.

5.
Nanomedicine ; 61: 102769, 2024 Jun 22.
Article in English | MEDLINE | ID: mdl-38914247

ABSTRACT

Many strategies for regenerating the damaged tissues or degenerating cells are employed in regenerative medicine. Stem cell technology is a modern strategy of the recent approaches, particularly the use of mesenchymal stem cells (MCSs). The ability of MSCs to differentiate as well as their characteristic behaviour as paracrine effector has established them as key elements in tissue repair (Shaer et al., 20141). Recently, extracellular vesicles (EVs) shed by MSCs have emerged as a promising cell free therapy (Citation}Rani, S., Ryan, A. E., Griffin, M. D., and Ritter, T., 20152). This comprehensive review encompasses MSCs-derived exosomes and their therapeutic potential as nanotherapeutics. We also discuss their potency as drug delivery nano-carriers in comparison with liposomes. A better knowledge of EVs behaviour in vivo and of their mechanism of action are key to determine parameters of an optimal formulation in pilot studies and to establish industrial processes.

6.
Int J Nanomedicine ; 19: 4877-4892, 2024.
Article in English | MEDLINE | ID: mdl-38828203

ABSTRACT

Botanical preparations for herbal medicine have received more and more attention from drug researchers, and the extraction of active ingredients and their successful clinical application have become an important direction of drug research in major pharmaceutical companies, but the complexity of extracts, multiple side effects, and significant individual differences have brought many difficulties to the clinical application of herbal preparations. It is noteworthy that extracellular vesicles as active biomolecules extracted from medicinal plants are believed to be useful for the treatment of a variety of diseases, including cancer, inflammation, regenerative-restorative and degenerative diseases, which may provide a new direction for the clinical utilization of herbal preparations. In this review, we sort out recent advances in medicinal plant extracellular vesicles and discuss their potential as disease therapeutics. Finally, future challenges and research directions for the clinical translation of medicinal plant extracellular vesicles are also discussed, and we expect that continued development based on medicinal plant extracellular vesicles will facilitate the clinical application of herbal preparations.


Subject(s)
Extracellular Vesicles , Plants, Medicinal , Animals , Humans , Extracellular Vesicles/chemistry , Neoplasms/drug therapy , Phytotherapy/methods , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Plants, Medicinal/cytology
7.
Theranostics ; 14(8): 3221-3245, 2024.
Article in English | MEDLINE | ID: mdl-38855177

ABSTRACT

The availability of non-invasive drug delivery systems capable of efficiently transporting bioactive molecules across the blood-brain barrier to specific cells at the injury site in the brain is currently limited. Delivering drugs to neurons presents an even more formidable challenge due to their lower numbers and less phagocytic nature compared to other brain cells. Additionally, the diverse types of neurons, each performing specific functions, necessitate precise targeting of those implicated in the disease. Moreover, the complex synthetic design of drug delivery systems often hinders their clinical translation. The production of nanomaterials at an industrial scale with high reproducibility and purity is particularly challenging. However, overcoming this challenge is possible by designing nanomaterials through a straightforward, facile, and easily reproducible synthetic process. Methods: In this study, we have developed a third-generation 2-deoxy-glucose functionalized mixed layer dendrimer (2DG-D) utilizing biocompatible and cost-effective materials via a highly facile convergent approach, employing copper-catalyzed click chemistry. We further evaluated the systemic neuronal targeting and biodistribution of 2DG-D, and brain delivery of a neuroprotective agent pioglitazone (Pio) in a pediatric traumatic brain injury (TBI) model. Results: The 2DG-D exhibits favorable characteristics including high water solubility, biocompatibility, biological stability, nanoscale size, and a substantial number of end groups suitable for drug conjugation. Upon systemic administration in a pediatric mouse model of traumatic brain injury (TBI), the 2DG-D localizes in neurons at the injured brain site, clears rapidly from off-target locations, effectively delivers Pio, ameliorates neuroinflammation, and improves behavioral outcomes. Conclusions: The promising in vivo results coupled with a convenient synthetic approach for the construction of 2DG-D makes it a potential nanoplatform for addressing brain diseases.


Subject(s)
Dendrimers , Deoxyglucose , Drug Delivery Systems , Neurons , Animals , Dendrimers/chemistry , Neurons/drug effects , Neurons/metabolism , Drug Delivery Systems/methods , Deoxyglucose/pharmacology , Deoxyglucose/pharmacokinetics , Neuroprotective Agents/pharmacokinetics , Neuroprotective Agents/administration & dosage , Neuroprotective Agents/pharmacology , Mice , Pioglitazone/pharmacology , Pioglitazone/administration & dosage , Pioglitazone/pharmacokinetics , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/metabolism , Brain/metabolism , Brain/drug effects , Brain Diseases/drug therapy , Humans , Disease Models, Animal , Tissue Distribution , Male
8.
J Control Release ; 370: 653-676, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38735396

ABSTRACT

Pyroptosis, a non-apoptotic programmed cellular inflammatory death mechanism characterized by gasdermin (GSDM) family proteins, has gathered significant attention in the cancer treatment. However, the alarming clinical trial data indicates that pyroptosis-mediated cancer therapeutic efficiency is still unsatisfactory. It is essential to integrate the burgeoning biomedical findings and innovations with potent technology to hasten the development of pyroptosis-based antitumor drugs. Considering the rapid development of pyroptosis-driven cancer nanotherapeutics, here we aim to summarize the recent advances in this field at the intersection of pyroptosis and nanotechnology. First, the foundation of pyroptosis-based nanomedicines (NMs) is outlined to illustrate the reliability and effectiveness for the treatment of tumor. Next, the emerging nanotherapeutics designed to induce pyroptosis are overviewed. Moreover, the cross-talk between pyroptosis and other cell death modalities are discussed, aiming to explore the mechanistic level relationships to provide guidance strategies for the combination of different types of antitumor drugs. Last but not least, the opportunities and challenges of employing pyroptosis-based NMs in potential clinical cancer therapy are highlighted.


Subject(s)
Antineoplastic Agents , Neoplasms , Pyroptosis , Pyroptosis/drug effects , Humans , Neoplasms/drug therapy , Neoplasms/therapy , Neoplasms/metabolism , Neoplasms/pathology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Animals , Nanomedicine/methods , Nanotechnology/methods , Nanoparticles/administration & dosage
9.
Pharmaceutics ; 16(5)2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38794248

ABSTRACT

A wide variety of natural bioactive compounds derived from plants have demonstrated significant clinical relevance in the treatment of various diseases such as cancer, chronic disease, and inflammation. An increasing number of studies have surfaced that give credence to the potential of plant-derived vesicle-like nanoparticles (PDVLNs) as compelling candidates for a drug delivery system (DDS). PDVLNs are cost-effective production, non-toxicity and non-immunogenicity and fascinating bi-ocompatibility. In this review, we attempt to comprehensively review and consolidate the position of PDVLNs as next-generation drug delivery nanoplatforms. We aim to give a quick glance to readers of the current developments of PDVLNs, including their biogenesis, characteristic features, composition, administration routes, advantages, and application. Further, we discuss the advantages and limitations of PDVLNs. We expect that the role of PDVLNs in drug delivery will be significantly enhanced, thus positioning them as the next generation of therapeutic modalities in the foreseeable future.

10.
Adv Healthc Mater ; : e2400809, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38752756

ABSTRACT

Chemodynamic therapy (CDT) has emerged as a transformative paradigm in the realm of reactive oxygen species -mediated cancer therapies, exhibiting its potential as a sophisticated strategy for precise and effective tumor treatment. CDT primarily relies on metal ions and hydrogen peroxide to initiate Fenton or Fenton-like reactions, generating cytotoxic hydroxyl radicals. Its notable advantages in cancer treatment are demonstrated, including tumor specificity, autonomy from external triggers, and a favorable side-effect profile. Recent advancements in nanomedicine are devoted to enhancing CDT, promising a comprehensive optimization of CDT efficacy. This review systematically elucidates cutting-edge achievements in chemodynamic nanotherapeutics, exploring strategies for enhanced Fenton or Fenton-like reactions, improved tumor microenvironment modulation, and precise regulation in energy metabolism. Moreover, a detailed analysis of diverse CDT-mediated combination therapies is provided. Finally, the review concludes with a comprehensive discussion of the prospects and intrinsic challenges to the application of chemodynamic nanotherapeutics in the domain of cancer treatment.

11.
Oncol Res ; 32(4): 769-784, 2024.
Article in English | MEDLINE | ID: mdl-38560569

ABSTRACT

Bone metastasis secondary to breast cancer negatively impacts patient quality of life and survival. The treatment of bone metastases is challenging since many anticancer drugs are not effectively delivered to the bone to exert a therapeutic effect. To improve the treatment efficacy, we developed Pluronic P123 (P123)-based polymeric micelles dually decorated with alendronate (ALN) and cancer-specific phage protein DMPGTVLP (DP-8) for targeted drug delivery to breast cancer bone metastases. Doxorubicin (DOX) was selected as the anticancer drug and was encapsulated into the hydrophobic core of the micelles with a high drug loading capacity (3.44%). The DOX-loaded polymeric micelles were spherical, 123 nm in diameter on average, and exhibited a narrow size distribution. The in vitro experiments demonstrated that a pH decrease from 7.4 to 5.0 markedly accelerated DOX release. The micelles were well internalized by cultured breast cancer cells and the cell death rate of micelle-treated breast cancer cells was increased compared to that of free DOX-treated cells. Rapid binding of the micelles to hydroxyapatite (HA) microparticles indicated their high affinity for bone. P123-ALN/DP-8@DOX inhibited tumor growth and reduced bone resorption in a 3D cancer bone metastasis model. In vivo experiments using a breast cancer bone metastasis nude model demonstrated increased accumulation of the micelles in the tumor region and considerable antitumor activity with no organ-specific histological damage and minimal systemic toxicity. In conclusion, our study provided strong evidence that these pH-sensitive dual ligand-targeted polymeric micelles may be a successful treatment strategy for breast cancer bone metastasis.


Subject(s)
Antineoplastic Agents , Bone Neoplasms , Breast Neoplasms , Poloxalene , Humans , Female , Micelles , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Ligands , Quality of Life , Cell Line, Tumor , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Polymers/chemistry , Polymers/therapeutic use , Antineoplastic Agents/therapeutic use , Drug Delivery Systems , Bone Neoplasms/drug therapy , Alendronate/pharmacology , Alendronate/chemistry , Alendronate/therapeutic use , Drug Carriers/chemistry , Drug Carriers/therapeutic use
12.
Article in English | MEDLINE | ID: mdl-38561624

ABSTRACT

Lung cancer remains a formidable challenge in oncology, necessitating the develop-ment of more effective prognostic and diagnostic techniques due to inefficient conventional therapeutic approaches and inadequate methods for early lung cancer diagnosis. Despite im-mense progress in the development of innovative strategies to alleviate the impact of this devas-tating disease, the outcomes, unfortunately, remain unsatisfactory, particularly in targeted drug delivery methods. Consequently, nanotechnology has emerged as a revolutionary force in cancer research to develop more effective targeted drug delivery tools due to its extraordinary capacity at the atomic and molecular levels. It has appeared as a beacon of hope in this area of unmet need, providing innovative ways for the prognosis and diagnosis of lung carcinoma. Therefore, this comprehensive review delves into the evolving field of nano-based therapeutics, shedding light on their potential to transform lung cancer treatment. This study meticulously explores the most promising nano-based strategies that have been extensively linked with the treatment of lung carcinoma and mainly emphasizes targeted drug delivery methods and therapies. Addition-ally, this review encapsulates the favorable results of clinical trials, which support the potential pathways for further development of nanotherapeutics in lung cancer management.

13.
J Nanobiotechnology ; 22(1): 160, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38589911

ABSTRACT

Dry eye disease (DED) is associated with ocular hyperosmolarity and inflammation. The marketed topical eye drops for DED treatment often lack bioavailability and precorneal residence time. In this study, we investigated catechol-functionalized polyzwitterion p(MPC-co-DMA), composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) and dopamine methacrylamide (DMA) monomers, as potential topical nanotherapeutics for DED. The copolymers were synthesized via random free-radical copolymerization, producing different proportions of catecholic functionalization. All as-prepared polymer compositions displayed good ocular biocompatibility. At a feeding ratio of 1:1, p(MPC1-co-DMA1) can facilitate a robust mucoadhesion via Michael addition and/or Schiff base reaction, thus prolonging ocular residence time after 4 days of topical instillation. The hydration lubrication of MPC and radical-scavenging DMA endow the nano-agent to ease tear-film hyperosmolarity and corneal inflammation. A single dose of p(MPC1-co-DMA1) (1 mg/mL) after 4 days post-instillation can protect the cornea against reactive oxygen species, inhibiting cell apoptosis and the over-expression of pro-inflammatory factors (IL-6 and TNF-α). In clinical assessment, DED-induced rabbit eyes receiving p(MPC1-co-DMA1) could increase lacrimal fluid secretion by 5-fold higher than cyclosporine A. The catechol-functionalized polyzwitterion with enhanced lubricity, mucoadhesion, and anti-oxidation/anti-inflammation properties has shown high promise as a bioactive eye drop formulation for treating DED.


Subject(s)
Antioxidants , Lubricants , Animals , Rabbits , Antioxidants/pharmacology , Biocompatible Materials , Anti-Inflammatory Agents , Ophthalmic Solutions , Catechols , Inflammation
14.
Bioorg Chem ; 146: 107331, 2024 May.
Article in English | MEDLINE | ID: mdl-38579614

ABSTRACT

Ferroptosis represents a non-apoptotic form of programmed cell death characterized by iron-dependent lipid peroxidation. This cell death modality not only facilitates the direct elimination of cancer cells, but also enhances their susceptibility to other pharmacological anti-cancer agents. The burgeoning interest in ferroptosis has been driven by a growing body of evidence that underscores the efficiency and minimal toxicity of ferroptosis inducers. Traditional inducers, such as erastin and RSL3 have shown substantial promise in clinical applications due to their potent therapeutic effects. Their significant potential of these inducers has spurred the development of a variety of small molecule ferroptosis inducers. These novel inducers boast an enhanced structural variety, improved metabolic stability, the capability to initiate ferroptosis without triggering apoptosis, making them well-suited for in vivo use. Despite these advancements, challenges still remain, particularly concerning the drug delivery, tumor specificity, and circulation duration of these small molecules in vivo. Addressing these challenges, contemporary research has pivoted towards innovative delivery systems tailored for ferroptosis inducers to facilitate precise, targeted, and synegestic therapeutic delivery. This review scrutinizes the latest progress in small molecule ferroptosis inducers and nano drug delivery systems geared towards ferroptosis sensitization. Furthermore, it delineated the prospective therapeutic advantages and the existing hurdles in the development of ferroptosis inducers for malignant tumor treatment.


Subject(s)
Antineoplastic Agents , Ferroptosis , Neoplasms , Humans , Apoptosis , Cell Death , Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
15.
Theranostics ; 14(6): 2490-2525, 2024.
Article in English | MEDLINE | ID: mdl-38646646

ABSTRACT

Inflammatory dysregulation is intimately associated with the occurrence and progression of many life-threatening diseases. Accurate detection and timely therapeutic intervention on inflammatory dysregulation are crucial for the effective therapy of inflammation-associated diseases. However, the clinical outcomes of inflammation-involved disorders are still unsatisfactory. Therefore, there is an urgent need to develop innovative anti-inflammatory strategies by integrating emerging technological innovations with traditional therapeutics. Biomedical nanotechnology is one of the promising fields that can potentially transform the diagnosis and treatment of inflammation. In this review, we outline recent advances in biomedical nanotechnology for the diagnosis and treatment of inflammation, with special attention paid to nanosensors and nanoprobes for precise diagnosis of inflammation-related diseases, emerging anti-inflammatory nanotherapeutics, as well as nanotheranostics and combined anti-inflammatory applications. Moreover, the prospects and challenges for clinical translation of nanoprobes and anti-inflammatory nanomedicines are highlighted.


Subject(s)
Inflammation , Nanotechnology , Theranostic Nanomedicine , Humans , Inflammation/diagnosis , Theranostic Nanomedicine/methods , Nanotechnology/methods , Animals , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/administration & dosage , Nanomedicine/methods , Nanoparticles
16.
J Cell Mol Med ; 28(8): e18302, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38652115

ABSTRACT

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision-driven approaches. Embracing this paradigm, our research probes the therapeutic efficacy of the aqueous crude extract (ACE) of Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis and showcasing prebiotic attributes. Characterization of ACE have identified several phytochemicals including significant presence of octadeconoic acid. Simultaneously, utilizing advanced Molecular Dynamics (MD) simulations, we deciphered the intricate molecular interactions between Vascular Endothelial Growth Factor (VEGF) and Octadecanoic acid to establish C.indica's role as an anticancer agent. Our study delineates Octadecanoic acid's potential as a robust binding partner for VEGF, with comprehensive analyses from RMSD and RMSF profiles highlighting the stability and adaptability of the protein-ligand interactions. Further in-depth thermodynamic explorations via MM-GBSA calculations reveal the binding landscape of the VEGF-Octadecanoic acid complex. Emerging therapeutic innovations, encompassing proteolysis-targeting chimeras (PROTACs) and avant-garde nanocarriers, are discussed in the context of their synergy with compounds like Calocybe indica P&C. This convergence underscores the profound therapeutic potential awaiting clinical exploration. This study offers a holistic perspective on the promising therapeutic avenues facilitated by C. indica against cervical cancer, intricately woven with advanced molecular interactions and the prospective integration of precision therapeutics in modern oncology.


Subject(s)
Molecular Dynamics Simulation , Plant Extracts , Uterine Cervical Neoplasms , Vascular Endothelial Growth Factor A , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/pathology , Humans , Vascular Endothelial Growth Factor A/metabolism , Female , Plant Extracts/pharmacology , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Precision Medicine/methods , Apoptosis/drug effects , Cell Line, Tumor , Protein Binding , Molecular Docking Simulation
17.
Arch Microbiol ; 206(4): 158, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38480540

ABSTRACT

Quantum Dots (QDs) have emerged as versatile nanomaterials with origins spanning organic, inorganic, and natural sources, revolutionizing various biomedical applications, particularly in combating pathogenic biofilm formation. Biofilms, complex structures formed by microbial communities enveloped in exopolysaccharide matrices, pose formidable challenges to traditional antibiotics due to their high tolerance and resistance, exacerbating inefficacy issues in antibiotic treatments. QDs offer a promising solution, employing physical mechanisms like photothermal or photodynamic therapy to disrupt biofilms. Their efficacy is noteworthy, with lower susceptibility to resistance development and broad-spectrum action as compared to conventional antibiotic methods. The stability and durability of QDs ensure sustained biofilm activity, even in challenging environmental conditions. This comprehensive review delves into the synthesis, properties, and applications of Carbon Quantum Dots (CQDs), most widely used QDs, showcasing groundbreaking developments that position these nanomaterials at the forefront of cutting-edge research and innovation. These nanomaterials exhibit multifaceted mechanisms, disrupting cell walls and membranes, generating reactive oxygen species (ROS), and binding to nucleic materials, effectively inhibiting microbial proliferation. This opens transformative possibilities for healthcare interventions by providing insights into biofilm dynamics. However, challenges in size control necessitate ongoing research to refine fabrication techniques, ensure defect-free surfaces, and optimize biological activity. QDs emerge as microscopic yet potent tools, promising to contribute to a brighter future where quantum wonders shape innovative solutions to persistently challenging issues posed by pathogenic biofilms. Henceforth, this review aims to explore QDs as potential agents for inhibiting pathogenic microbial biofilms, elucidating the underlying mechanisms, addressing the current challenges, and highlighting their promising future potential.


Subject(s)
Nanostructures , Quantum Dots , Quantum Dots/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Biofilms , Carbon
18.
ACS Appl Bio Mater ; 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38530292

ABSTRACT

The discovery of specifically tailored therapeutic delivery systems has sparked the interest of pharmaceutical researchers considering improved therapeutic effectiveness and fewer adverse effects. The current study concentrates on the design and characterization of PLGA (polylactic-co-glycolic acid) capped mesoporous silica nanoparticles (MSN)-based systems for drug delivery for pH-sensitive controlled drug release in order to achieve a targeted drug release inside the acidic tumor microenvironment. The physicochemical properties of the nanoformulations were analyzed using TEM, zeta potential, AFM, TGA, FTIR, and BET analyses in addition to DLS size. The final formed PLGA-FoA-MSN-CAP and pure MSN had sizes within the therapeutic ranges of 164.5 ± 1.8 and 110.7 ± 2.2, respectively. Morphological characterization (TEM and AFM) and elemental analysis (FTIR and XPS) confirmed the proper capping and tagging of PLGA and folic acid (FoA). The PLGA-coated FoA-MSN exhibited a pH-dependent controlled release of the CAP (capecitabine) drug, showing efficient release at pH 6.8. Furthermore, the in vitro MTT test on PANC1 and MIAPaCa-2 resulted in an IC50 value of 146.37 µg/ml and 105.90 µg/ml, respectively. Mitochondrial-mediated apoptosis was confirmed from the caspase-3 and annexin V/PI flow cytometry assay, which displayed a cell cycle arrest at the G1 phase. Overall, the results predicted that the designed nanoformulation is a potential therapeutic agent in treating pancreatic cancer.

19.
Cell Commun Signal ; 22(1): 188, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38519959

ABSTRACT

Methicillin-resistant Staphylococcus aureus (MRSA) represents a global threat, necessitating the development of effective solutions to combat this emerging superbug. In response to selective pressures within healthcare, community, and livestock settings, MRSA has evolved increased biofilm formation as a multifaceted virulence and defensive mechanism, enabling the bacterium to thrive in harsh conditions. This review discusses the molecular mechanisms contributing to biofilm formation across its developmental stages, hence representing a step forward in developing promising strategies for impeding or eradicating biofilms. During staphylococcal biofilm development, cell wall-anchored proteins attach bacterial cells to biotic or abiotic surfaces; extracellular polymeric substances build scaffolds for biofilm formation; the cidABC operon controls cell lysis within the biofilm, and proteases facilitate dispersal. Beside the three main sequential stages of biofilm formation (attachment, maturation, and dispersal), this review unveils two unique developmental stages in the biofilm formation process for MRSA; multiplication and exodus. We also highlighted the quorum sensing as a cell-to-cell communication process, allowing distant bacterial cells to adapt to the conditions surrounding the bacterial biofilm. In S. aureus, the quorum sensing process is mediated by autoinducing peptides (AIPs) as signaling molecules, with the accessory gene regulator system playing a pivotal role in orchestrating the production of AIPs and various virulence factors. Several quorum inhibitors showed promising anti-virulence and antibiofilm effects that vary in type and function according to the targeted molecule. Disrupting the biofilm architecture and eradicating sessile bacterial cells are crucial steps to prevent colonization on other surfaces or organs. In this context, nanoparticles emerge as efficient carriers for delivering antimicrobial and antibiofilm agents throughout the biofilm architecture. Although metal-based nanoparticles have been previously used in combatting biofilms, its non-degradability and toxicity within the human body presents a real challenge. Therefore, organic nanoparticles in conjunction with quorum inhibitors have been proposed as a promising strategy against biofilms. As nanotherapeutics continue to gain recognition as an antibiofilm strategy, the development of more antibiofilm nanotherapeutics could offer a promising solution to combat biofilm-mediated resistance.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Humans , Methicillin-Resistant Staphylococcus aureus/physiology , Staphylococcus aureus , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Biofilms , Quorum Sensing/genetics
20.
Curr Top Med Chem ; 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38445699

ABSTRACT

During the last five decades, there has been tremendous development in our understanding of cancer biology and the development of new and novel therapeutics to target cancer. However, despite these advances, cancer remains the second leading cause of death across the globe. Most cancer deaths are attributed to the development of resistance to current therapies. There is an urgent and unmet need to address cancer therapy resistance. Tetrandrine, a bis-benzyl iso-quinoline, has shown a promising role as an anti-cancer agent. Recent work from our laboratory and others suggests that tetrandrine and its derivatives could be an excellent adjuvant to the current arsenal of anti-cancer drugs. Herein, we provide an overview of resistance mechanisms to current therapeutics and review the existing literature on the anti-cancer effects of tetrandrine and its potential use for overcoming therapy resistance in cancer.

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