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20 pages, 2444 KiB  
Review
Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes as Nanomedicine for Peripheral Nerve Injury
by Qicheng Li, Fengshi Zhang, Xiaoyang Fu and Na Han
Int. J. Mol. Sci. 2024, 25(14), 7882; https://doi.org/10.3390/ijms25147882 (registering DOI) - 18 Jul 2024
Viewed by 81
Abstract
Peripheral nerve injury (PNI) is a complex and protracted process, and existing therapeutic approaches struggle to achieve effective nerve regeneration. Recent studies have shown that mesenchymal stem cells (MSCs) may be a pivotal choice for treating peripheral nerve injury. MSCs possess robust paracrine [...] Read more.
Peripheral nerve injury (PNI) is a complex and protracted process, and existing therapeutic approaches struggle to achieve effective nerve regeneration. Recent studies have shown that mesenchymal stem cells (MSCs) may be a pivotal choice for treating peripheral nerve injury. MSCs possess robust paracrine capabilities, and exosomes, as the primary secretome of MSCs, are considered crucial regulatory mediators involved in peripheral nerve regeneration. Exosomes, as nanocarriers, can transport various endogenous or exogenous bioactive substances to recipient cells, thereby promoting vascular and axonal regeneration while suppressing inflammation and pain. In this review, we summarize the mechanistic roles of exosomes derived from MSCs in peripheral nerve regeneration, discuss the engineering strategies for MSC-derived exosomes to improve therapeutic potential, and explore the combined effects of MSC-derived exosomes with biomaterials (nerve conduits, hydrogels) in peripheral nerve regeneration. Full article
(This article belongs to the Special Issue Peripheral Neuropathies: Molecular Research and Novel Therapy)
18 pages, 3368 KiB  
Article
Mitochondria-Targeted Liposomes for Drug Delivery to Tumor Mitochondria
by Aysegul Ekmekcioglu, Ozgul Gok, Devrim Oz-Arslan, Meryem Sedef Erdal, Yasemin Yagan Uzuner and Meltem Muftuoglu
Pharmaceutics 2024, 16(7), 950; https://doi.org/10.3390/pharmaceutics16070950 (registering DOI) - 17 Jul 2024
Viewed by 173
Abstract
The special bilayer structure of mitochondrion is a promising therapeutic target in the diagnosis and treatment of diseases such as cancer and metabolic diseases. Nanocarriers such as liposomes modified with mitochondriotropic moieties can be developed to send therapeutic molecules to mitochondria. In this [...] Read more.
The special bilayer structure of mitochondrion is a promising therapeutic target in the diagnosis and treatment of diseases such as cancer and metabolic diseases. Nanocarriers such as liposomes modified with mitochondriotropic moieties can be developed to send therapeutic molecules to mitochondria. In this study, DSPE-PEG-TPP polymer conjugate was synthesized and used to prepare mitochondria-targeted liposomes (TPPLs) to improve the therapeutic index of chemotherapeutic agents functioning in mitochondria and reduce their side effects. Doxorubicin (Dox) loaded-TPPL and non-targeted PEGylated liposomes (PPLs) were prepared and compared based on physicochemical properties, morphology, release profile, cellular uptake, mitochondrial localization, and anticancer effects. All formulations were spherically shaped with appropriate size, dispersity, and zeta potential. The stability of the liposomes was favorable for two months at 4 °C. TPPLs localize to mitochondria, whereas PPLs do not. The empty TPPLs and PPLs were not cytotoxic to HCT116 cells. The release kinetics of Dox-loaded liposomes showed that Dox released from TPPLs was higher at pH 5.6 than at pH 7.4, which indicates a higher accumulation of the released drug in the tumor environment. The half-maximal inhibitory concentration of Dox-loaded TPPLs and PPLs was 1.62-fold and 1.17-fold lower than that of free Dox due to sustained drug release, respectively. The reactive oxygen species level was significantly increased when HCT116 cells were treated with Dox-loaded TPPLs. In conclusion, TPPLs may be promising carriers for targeted drug delivery to tumor mitochondria. Full article
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17 pages, 2901 KiB  
Review
Roles of Two-Dimensional Materials in Antibiofilm Applications: Recent Developments and Prospects
by Lei Xin, Hongkun Zhao, Min Peng and Yuanjie Zhu
Pharmaceuticals 2024, 17(7), 950; https://doi.org/10.3390/ph17070950 - 16 Jul 2024
Viewed by 281
Abstract
Biofilm-associated infections pose a significant challenge in healthcare, constituting 80% of bacterial infections and often leading to persistent, chronic conditions. Conventional antibiotics struggle with efficacy against these infections due to the high tolerance and resistance induced by bacterial biofilm barriers. Two-dimensional nanomaterials, such [...] Read more.
Biofilm-associated infections pose a significant challenge in healthcare, constituting 80% of bacterial infections and often leading to persistent, chronic conditions. Conventional antibiotics struggle with efficacy against these infections due to the high tolerance and resistance induced by bacterial biofilm barriers. Two-dimensional nanomaterials, such as those from the graphene family, boron nitride, molybdenum disulfide (MoS2), MXene, and black phosphorus, hold immense potential for combating biofilms. These nanomaterial-based antimicrobial strategies are novel tools that show promise in overcoming resistant bacteria and stubborn biofilms, with the ability to circumvent existing drug resistance mechanisms. This review comprehensively summarizes recent developments in two-dimensional nanomaterials, as both therapeutics and nanocarriers for precision antibiotic delivery, with a specific focus on nanoplatforms coupled with photothermal/photodynamic therapy in the elimination of bacteria and penetrating and/or ablating biofilm. This review offers important insight into recent advances and current limitations of current antibacterial nanotherapeutic approaches, together with a discussion on future developments in the field, for the overall benefit of public health. Full article
(This article belongs to the Section Biopharmaceuticals)
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16 pages, 1566 KiB  
Review
Recent Advances of Natural Pentacyclic Triterpenoids as Bioactive Delivery System for Synergetic Biological Applications
by Wendi Teng, Zixiao Zhou, Jinxuan Cao and Qing Guo
Foods 2024, 13(14), 2226; https://doi.org/10.3390/foods13142226 - 16 Jul 2024
Viewed by 366
Abstract
Bioactive compounds have drawn much attention according to their various health benefits. However, poor dissolvability, low stability and limited bioavailability largely narrow their applications. Although a variety of nontoxic ingredients have been rapidly developed as vehicles to deliver bioactive compounds in the last [...] Read more.
Bioactive compounds have drawn much attention according to their various health benefits. However, poor dissolvability, low stability and limited bioavailability largely narrow their applications. Although a variety of nontoxic ingredients have been rapidly developed as vehicles to deliver bioactive compounds in the last few years, most of them are non-bioactive. Pentacyclic triterpenoids, owing to their unique self-assembly and co-assembly behaviors and different physiological functions, can construct bioactive carriers due to their higher biodegradability, biocompatibility and lower toxicity. In this paper, the basic classification, biological activities and physicochemical properties of pentacyclic triterpenoids were summarized. Additionally, applications of self-assembled and co-assembled pentacyclic triterpenoids as bioactive delivery systems to load bioactive components and future research directions were discussed. This study emphasizes the potential of pentacyclic triterpenoids as bioactive delivery systems, offering a new perspective for constructing self- or co-assemblies for further synergetic biological applications. Full article
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27 pages, 4126 KiB  
Review
Advances in Nanomedicine for Precision Insulin Delivery
by Alfredo Caturano, Roberto Nilo, Davide Nilo, Vincenzo Russo, Erica Santonastaso, Raffaele Galiero, Luca Rinaldi, Marcellino Monda, Celestino Sardu, Raffaele Marfella and Ferdinando Carlo Sasso
Pharmaceuticals 2024, 17(7), 945; https://doi.org/10.3390/ph17070945 - 15 Jul 2024
Viewed by 269
Abstract
Diabetes mellitus, which comprises a group of metabolic disorders affecting carbohydrate metabolism, is characterized by improper glucose utilization and excessive production, leading to hyperglycemia. The global prevalence of diabetes is rising, with projections indicating it will affect 783.2 million people by 2045. Insulin [...] Read more.
Diabetes mellitus, which comprises a group of metabolic disorders affecting carbohydrate metabolism, is characterized by improper glucose utilization and excessive production, leading to hyperglycemia. The global prevalence of diabetes is rising, with projections indicating it will affect 783.2 million people by 2045. Insulin treatment is crucial, especially for type 1 diabetes, due to the lack of β-cell function. Intensive insulin therapy, involving multiple daily injections or continuous subcutaneous insulin infusion, has proven effective in reducing microvascular complications but poses a higher risk of severe hypoglycemia. Recent advancements in insulin formulations and delivery methods, such as ultra-rapid-acting analogs and inhaled insulin, offer potential benefits in terms of reducing hypoglycemia and improving glycemic control. However, the traditional subcutaneous injection method has drawbacks, including patient compliance issues and associated complications. Nanomedicine presents innovative solutions to these challenges, offering promising avenues for overcoming current drug limitations, enhancing cellular uptake, and improving pharmacokinetics and pharmacodynamics. Various nanocarriers, including liposomes, chitosan, and PLGA, provide protection against enzymatic degradation, improving drug stability and controlled release. These nanocarriers offer unique advantages, ranging from enhanced bioavailability and sustained release to specific targeting capabilities. While oral insulin delivery is being explored for better patient adherence and cost-effectiveness, other nanomedicine-based methods also show promise in improving delivery efficiency and patient outcomes. Safety concerns, including potential toxicity and immunogenicity issues, must be addressed, with the FDA providing guidance for the safe development of nanotechnology-based products. Future directions in nanomedicine will focus on creating next-generation nanocarriers with precise targeting, real-time monitoring, and stimuli-responsive features to optimize diabetes treatment outcomes and patient safety. This review delves into the current state of nanomedicine for insulin delivery, examining various types of nanocarriers and their mechanisms of action, and discussing the challenges and future directions in developing safe and effective nanomedicine-based therapies for diabetes management. Full article
(This article belongs to the Special Issue Advancements in Cardiovascular and Antidiabetic Drug Therapy)
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20 pages, 16526 KiB  
Article
The Potential of Photodynamic Therapy Using Solid Lipid Nanoparticles with Aluminum Phthalocyanine Chloride as a Nanocarrier for Modulating Immunogenic Cell Death in Murine Melanoma In Vitro
by Marina M. Simões, Karen L. R. Paiva, Isadora Florêncio de Souza, Victor Carlos Mello, Ingrid Gracielle Martins da Silva, Paulo Eduardo Narcizo Souza, Luis Alexandre Muehlmann and Sônia Nair Báo
Pharmaceutics 2024, 16(7), 941; https://doi.org/10.3390/pharmaceutics16070941 - 14 Jul 2024
Viewed by 450
Abstract
Photodynamic therapy (PDT) uses a photosensitizer to generate reactive oxygen species (ROS) that kill target cells. In cancer treatments, PDT can potentially induce immunogenic cell death (ICD), which is characterized by a well-controlled exposure of damage-associated molecular patterns (DAMPs) that activate dendritic cells [...] Read more.
Photodynamic therapy (PDT) uses a photosensitizer to generate reactive oxygen species (ROS) that kill target cells. In cancer treatments, PDT can potentially induce immunogenic cell death (ICD), which is characterized by a well-controlled exposure of damage-associated molecular patterns (DAMPs) that activate dendritic cells (DCs) and consequently modulate the immune response in the tumor microenvironment. However, PDT still has limitations, such as the activity of photosensitizers in aqueous media and poor bioavailability. Therefore, a new photosensitizer system, SLN-AlPc, has been developed to improve the therapeutic efficacy of PDT. In vitro experiments showed that the light-excited nanocarrier increased ROS production in murine melanoma B16-F10 cells and modulated the profile of DCs. PDT induced cell death accompanied by the exposure of DAMPs and the formation of autophagosomes. In addition, the DCs exposed to PDT-treated B16-F10 cells exhibited morphological changes, increased expression of MHCII, CD86, CD80, and production of IL-12 and IFN-γ, suggesting immune activation towards an antitumor profile. These results indicate that the SLNs-AlPc protocol has the potential to improve PDT efficacy by inducing ICD and activating DCs. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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26 pages, 5180 KiB  
Review
Mesenchymal Stem Cell-Derived Exosomes as Drug Delivery Vehicles in Disease Therapy
by Wenzhe Zhao, Kaixuan Li, Liangbo Li, Ruichen Wang, Yang Lei, Hui Yang and Leming Sun
Int. J. Mol. Sci. 2024, 25(14), 7715; https://doi.org/10.3390/ijms25147715 - 14 Jul 2024
Viewed by 413
Abstract
Exosomes are small vesicles containing proteins, nucleic acids, and biological lipids, which are responsible for intercellular communication. Studies have shown that exosomes can be utilized as effective drug delivery vehicles to accurately deliver therapeutic substances to target tissues, enhancing therapeutic effects and reducing [...] Read more.
Exosomes are small vesicles containing proteins, nucleic acids, and biological lipids, which are responsible for intercellular communication. Studies have shown that exosomes can be utilized as effective drug delivery vehicles to accurately deliver therapeutic substances to target tissues, enhancing therapeutic effects and reducing side effects. Mesenchymal stem cells (MSCs) are a class of stem cells widely used for tissue engineering, regenerative medicine, and immunotherapy. Exosomes derived from MSCs have special immunomodulatory functions, low immunogenicity, the ability to penetrate tumor tissues, and high yield, which are expected to be engineered into efficient drug delivery systems. Despite the promising promise of MSC-derived exosomes, exploring their optimal preparation methods, drug-loading modalities, and therapeutic potential remains challenging. Therefore, this article reviews the related characteristics, preparation methods, application, and potential risks of MSC-derived exosomes as drug delivery systems in order to find potential therapeutic breakthroughs. Full article
(This article belongs to the Special Issue Nanoparticles in Nanobiotechnology and Nanomedicine: 2nd Edition)
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11 pages, 2210 KiB  
Article
Development of an RNA Nanostructure for Effective Botrytis cinerea Control through Spray-Induced Gene Silencing without an Extra Nanocarrier
by Fangli Wu, Ling Yan, Xiayang Zhao, Chongrun Lv and Weibo Jin
J. Fungi 2024, 10(7), 483; https://doi.org/10.3390/jof10070483 - 14 Jul 2024
Viewed by 394
Abstract
Spray-induced gene silencing represents an eco-friendly approach for crop protection through the use of double-stranded RNA (dsRNA) to activate the RNA interference (RNAi) pathway, thereby silencing crucial genes in pathogens. The major challenges associated with dsRNA are its limited stability and poor cellular [...] Read more.
Spray-induced gene silencing represents an eco-friendly approach for crop protection through the use of double-stranded RNA (dsRNA) to activate the RNA interference (RNAi) pathway, thereby silencing crucial genes in pathogens. The major challenges associated with dsRNA are its limited stability and poor cellular uptake, necessitating repeated applications for effective crop protection. In this study, RNA nanoparticles (NPs) were proposed as effectors in plants and pathogens by inducing the RNAi pathway and silencing gene expression. RNA structural motifs, such as hairpin-loop, kissing-loop, and tetra-U motifs, were used to link multiple siRNAs into a long, single-stranded RNA (lssRNA). The lssRNA, synthesized in Escherichia coli, self-assembled into stable RNA nanostructures via local base pairing. Comparative analyses between dsRNA and RNA NPs revealed that the latter displayed superior efficacy in inhibiting spore germination and mycelial growth of Botrytis cinerea. Moreover, RNA NPs had a more robust protective effect on plants against B. cinerea than did dsRNA. In addition, RNA squares are processed into expected siRNA in plants, thereby inhibiting the expression of the target gene. These findings suggest the potential of RNA NPs for use in plant disease control by providing a more efficient and specific alternative to dsRNA without requiring nanocarriers. Full article
(This article belongs to the Special Issue Control of Postharvest Fungal Diseases)
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25 pages, 6729 KiB  
Article
Biocompatible Preparation of Beta-Lactoglobulin/Chondroitin Sulfate Carrier Nanoparticles and Modification of Their Colloidal and Hydropathic Properties by Tween 80
by Ioannis Pispas, Nikolaos Spiliopoulos and Aristeidis Papagiannopoulos
Polymers 2024, 16(14), 1995; https://doi.org/10.3390/polym16141995 - 12 Jul 2024
Viewed by 317
Abstract
The electrostatic complexation of the protein beta-lactoglobulin (β-LG) with the anionic polysaccharide chondroitin sulfate (CS) and the subsequent stabilization by thermal treatment were studied to achieve the well-defined nanoparticles (NPs). The formation of the well-defined NPs was obtained at pH 4 with a [...] Read more.
The electrostatic complexation of the protein beta-lactoglobulin (β-LG) with the anionic polysaccharide chondroitin sulfate (CS) and the subsequent stabilization by thermal treatment were studied to achieve the well-defined nanoparticles (NPs). The formation of the well-defined NPs was obtained at pH 4 with a hydrodynamic radius from 60 to 80 nm. NP aggregation was observed at pH 1.5 because of the loss of the anionic charge of chondroitin sulfate on the surface of the NPs. After thermal treatment, the NPs exhibited stability against a pH increase to pH 7 while a stronger aggregation at pH 1.5 was observed. Core-shell structures were found at pH 7 after thermal treatment, indicating a possible mechanism of partial disintegration. The addition of Tween 80 (T80) before thermal treatment led to the formation of T80 self-assemblies inside the NPs. This caused an increase in the hydrophobicity of the inner and outer surfaces of the NPs as it was observed by fluorescence spectroscopy. The ζ-potential of the complexes and NPs was about −20 mV while the presence of T80 did not affect it. FTIR spectra verified changes of the secondary structure of β-LG in its complexes with CS and T80. The thermally treated NPs exhibited high surface and overall hydrophobicity and stability in high salinity and biocompatible solutions. The thermally treated NPs showed colloidal and physicochemical stability for 1 month, which were enhanced by the addition of T80. Due to the nature of the precursors and their colloidal properties, the NPs are highly promising for applications as biocompatible drug delivery nanocarriers while T80 acts as an agent to modify their properties. Full article
(This article belongs to the Section Biomacromolecules, Biobased and Biodegradable Polymers)
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26 pages, 5947 KiB  
Article
Lentisk (Pistacia lentiscus) Oil Nanoemulsions Loaded with Levofloxacin: Phytochemical Profiles and Antibiofilm Activity against Staphylococcus spp.
by Linda Maurizi, Alba Lasalvia, Maria Gioia Fabiano, Eleonora D’Intino, Francesca Del Cioppo, Caterina Fraschetti, Antonello Filippi, Maria Grazia Ammendolia, Antonietta Lucia Conte, Jacopo Forte, Davide Corinti, Maria Elisa Crestoni, Maria Carafa, Carlotta Marianecci, Federica Rinaldi and Catia Longhi
Pharmaceutics 2024, 16(7), 927; https://doi.org/10.3390/pharmaceutics16070927 - 11 Jul 2024
Viewed by 351
Abstract
Most clinical isolates of both Staphylococcus aureus and Staphylococcus epidermidis show the capacity to adhere to abiotic surfaces and to develop biofilms resulting in a contribution to chronic human skin infections. Antibiotic resistance and poor biofilm penetration are the main causes of ineffective therapeutic treatment [...] Read more.
Most clinical isolates of both Staphylococcus aureus and Staphylococcus epidermidis show the capacity to adhere to abiotic surfaces and to develop biofilms resulting in a contribution to chronic human skin infections. Antibiotic resistance and poor biofilm penetration are the main causes of ineffective therapeutic treatment in killing bacteria within biofilms. A possible strategy could be represented by drug delivery systems, such as nanoemulsions (composed of bioactive oil, surfactant and water phase), which are useful for enhancing the drug permeation of a loaded drug inside the biofilm and its activity. Phytochemical characterization of Pistacia lentiscus oil (LO) by direct infusion Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) allowed the identification of bioactive compounds with antimicrobial properties, including fatty acids and phenolic compounds. Several monoterpenes and sesquiterpenes have been also detected and confirmed by gas chromatography–mass spectrometric (GC-MS) analysis, together providing a complete metabolomic profiling of LO. In the present study, a nanoemulsion composed of LO has been employed for improving Levofloxacin water solubility. A deep physical–chemical characterization of the nanoemulsion including hydrodynamic diameter, ζ-potential, morphology, entrapment efficiency, stability release and permeation studies was performed. Additionally, the antimicrobial/antibiofilm activity of these preparations was evaluated against reference and clinical Staphylococcus spp. strains. In comparison to the free-form antibiotic, the loaded NE nanocarriers exhibited enhanced antimicrobial activity against the sessile forms of Staphylococcus spp. strains. Full article
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29 pages, 1076 KiB  
Review
High-Tech Sustainable Beauty: Exploring Nanotechnology for the Development of Cosmetics Using Plant and Animal By-Products
by Gabriela Braga Barros Nhani, Leonardo Delello Di Filippo, Geanne Aparecida de Paula, Vitoria Ribeiro Mantovanelli, Patricia Pereira da Fonseca, Felipe Mota Tashiro, Diana Coêlho Monteiro, Bruno Fonseca-Santos, Jonatas L. Duarte and Marlus Chorilli
Cosmetics 2024, 11(4), 112; https://doi.org/10.3390/cosmetics11040112 - 6 Jul 2024
Viewed by 630
Abstract
In a world increasingly focused on eco-conscious living, the cosmetic industry is actively adopting nanotechnology to transform plant and animal by-products into high-value beauty products. This comprehensive review explores the innovative and sustainable approaches for extracting and utilizing bioactive compounds from these by-products. [...] Read more.
In a world increasingly focused on eco-conscious living, the cosmetic industry is actively adopting nanotechnology to transform plant and animal by-products into high-value beauty products. This comprehensive review explores the innovative and sustainable approaches for extracting and utilizing bioactive compounds from these by-products. The application of nanocarrier systems is highlighted for their role in enhancing the delivery efficacy and safety of these ingredients in skincare and beauty products. Consumer demand and environmental concerns drive the shift towards natural and sustainable cosmetic products. Traditional cosmetic production often involves significant ecological impacts, prompting the industry to seek greener alternatives. This review addresses the critical need for sustainable beauty solutions that align with global sustainability goals, particularly those outlined in the 2030 Agenda for Sustainable Development. The review provides valuable insights into current trends and future directions in sustainable cosmetics by focusing on nanotechnology and by-products. The review uniquely integrates nanotechnology with sustainability practices in the cosmetic industry. It details the benefits of using nanocarriers to improve the stability, bioavailability, and efficacy of bioactive compounds derived from natural waste. This intersection of high-tech methodologies and sustainability offers a novel perspective on cosmetic innovation. Future research should focus on overcoming the technical, regulatory, and economic challenges of scaling up nanotechnology applications. Investigations should include the development of transparent supply chains, standardization methods for characterizing nanoparticles, and comprehensive lifecycle assessments to ensure environmental safety. Additionally, fostering collaboration between scientific research, industry practices, and consumer education is vital for advancing sustainable practices. This review contributes to the broader discourse on sustainable beauty by presenting a clear pathway for integrating these innovative approaches. It ensures that future cosmetic products meet consumer expectations for efficacy and safety and promote environmental stewardship and a circular economy, ultimately benefiting both the skin and the planet. Full article
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39 pages, 3049 KiB  
Review
Receptor-Targeted Nanomedicine for Cancer Therapy
by Arvee Prajapati, Shagun Rangra, Rashmi Patil, Nimeet Desai, Vaskuri G. S. Sainaga Jyothi, Sagar Salave, Prakash Amate, Derajram Benival and Nagavendra Kommineni
Receptors 2024, 3(3), 323-361; https://doi.org/10.3390/receptors3030016 - 3 Jul 2024
Viewed by 832
Abstract
Receptor-targeted drug delivery has been extensively explored for active targeting of therapeutic moiety in cancer treatment. In this review, we discuss the receptors that are overexpressed on tumor cells and have the potential to be targeted by nanocarrier systems for cancer treatment. We [...] Read more.
Receptor-targeted drug delivery has been extensively explored for active targeting of therapeutic moiety in cancer treatment. In this review, we discuss the receptors that are overexpressed on tumor cells and have the potential to be targeted by nanocarrier systems for cancer treatment. We also highlight the different types of nanocarrier systems and targeting ligands that researchers have explored. Our discussion covers various therapeutic modalities, including small molecules, aptamers, peptides, antibodies, and cell-based targeting strategies, and focuses on clinical developments. Additionally, this article highlights the challenges that arise during the clinical translation of nanocarrier-based targeting strategies. It also provides future directions for improving research in the area of clinically translatable cancer-targeted therapy to improve treatment efficacy while minimizing toxicity. Full article
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31 pages, 8636 KiB  
Review
Stimulus-Responsive Hydrogels for Targeted Cancer Therapy
by Raghu Solanki and Dhiraj Bhatia
Gels 2024, 10(7), 440; https://doi.org/10.3390/gels10070440 - 1 Jul 2024
Viewed by 786
Abstract
Cancer is a highly heterogeneous disease and remains a global health challenge affecting millions of human lives worldwide. Despite advancements in conventional treatments like surgery, chemotherapy, and immunotherapy, the rise of multidrug resistance, tumor recurrence, and their severe side effects and the complex [...] Read more.
Cancer is a highly heterogeneous disease and remains a global health challenge affecting millions of human lives worldwide. Despite advancements in conventional treatments like surgery, chemotherapy, and immunotherapy, the rise of multidrug resistance, tumor recurrence, and their severe side effects and the complex nature of the tumor microenvironment (TME) necessitates innovative therapeutic approaches. Recently, stimulus-responsive nanomedicines designed to target TME characteristics (e.g., pH alterations, redox conditions, enzyme secretion) have gained attention for their potential to enhance anticancer efficacy while minimizing the adverse effects of chemotherapeutics/bioactive compounds. Among the various nanocarriers, hydrogels are intriguing due to their high-water content, adjustable mechanical characteristics, and responsiveness to external and internal stimuli, making them promising candidates for cancer therapy. These properties make hydrogels an ideal nanocarrier for controlled drug release within the TME. This review comprehensively surveys the latest advancements in the area of stimulus-responsive hydrogels for cancer therapy, exploring various stimuli-responsive mechanisms, including biological (e.g., pH, redox), chemical (e.g., enzymes, glucose), and physical (e.g., temperature, light), as well as dual- or multi-stimuli responsiveness. Furthermore, this review addresses the current developments and challenges in hydrogels in cancer treatment. Our aim is to provide readers with a comprehensive understanding of stimulus-responsive hydrogels for cancer treatment, offering novel perspectives on their development for cancer therapy and other medical applications. Full article
(This article belongs to the Special Issue Stimuli-Responsive Composite Gels)
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28 pages, 3697 KiB  
Review
Achieving Endo/Lysosomal Escape Using Smart Nanosystems for Efficient Cellular Delivery
by Nimeet Desai, Dhwani Rana, Sagar Salave, Derajram Benival, Dignesh Khunt and Bhupendra G. Prajapati
Molecules 2024, 29(13), 3131; https://doi.org/10.3390/molecules29133131 - 1 Jul 2024
Viewed by 773
Abstract
The delivery of therapeutic agents faces significant hurdles posed by the endo-lysosomal pathway, a bottleneck that hampers clinical effectiveness. This comprehensive review addresses the urgent need to enhance cellular delivery mechanisms to overcome these obstacles. It focuses on the potential of smart nanomaterials, [...] Read more.
The delivery of therapeutic agents faces significant hurdles posed by the endo-lysosomal pathway, a bottleneck that hampers clinical effectiveness. This comprehensive review addresses the urgent need to enhance cellular delivery mechanisms to overcome these obstacles. It focuses on the potential of smart nanomaterials, delving into their unique characteristics and mechanisms in detail. Special attention is given to their ability to strategically evade endosomal entrapment, thereby enhancing therapeutic efficacy. The manuscript thoroughly examines assays crucial for understanding endosomal escape and cellular uptake dynamics. By analyzing various assessment methods, we offer nuanced insights into these investigative approaches’ multifaceted aspects. We meticulously analyze the use of smart nanocarriers, exploring diverse mechanisms such as pore formation, proton sponge effects, membrane destabilization, photochemical disruption, and the strategic use of endosomal escape agents. Each mechanism’s effectiveness and potential application in mitigating endosomal entrapment are scrutinized. This paper provides a critical overview of the current landscape, emphasizing the need for advanced delivery systems to navigate the complexities of cellular uptake. Importantly, it underscores the transformative role of smart nanomaterials in revolutionizing cellular delivery strategies, leading to a paradigm shift towards improved therapeutic outcomes. Full article
(This article belongs to the Special Issue New Nanomaterials for Diagnostic and Drug Delivery)
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13 pages, 2344 KiB  
Article
Exploring Disulfiram’s Anticancer Potential: PLGA Nano-Carriers for Prolonged Drug Delivery and Potential Improved Therapeutic Efficacy
by Ibrahim Dumbuya, Ana Maria Pereira, Ibrahim Tolaymat, Adnan Al Dalaty, Basel Arafat, Matt Webster, Barbara Pierscionek, Mouhamad Khoder and Mohammad Najlah
Nanomaterials 2024, 14(13), 1133; https://doi.org/10.3390/nano14131133 - 30 Jun 2024
Viewed by 640
Abstract
Disulfiram (DS) has been shown to have potent anti-cancer activity; however, it is also characterised by its low water solubility and rapid metabolism in vivo. Biodegradable polylactic-co-glycolic acid (PLGA) polymers have been frequently employed in the manufacturing of PLGA nano-carrier drug delivery systems. [...] Read more.
Disulfiram (DS) has been shown to have potent anti-cancer activity; however, it is also characterised by its low water solubility and rapid metabolism in vivo. Biodegradable polylactic-co-glycolic acid (PLGA) polymers have been frequently employed in the manufacturing of PLGA nano-carrier drug delivery systems. Thus, to develop DS-loaded PLGA nanoparticles (NPs) capable of overcoming DS’s limitations, two methodologies were used to formulate the NPs: direct nanoprecipitation (DNP) and single emulsion/solvent evaporation (SE), followed by particle size reduction. The DNP method was demonstrated to produce NPs of superior characteristics in terms of size (151.3 nm), PDI (0.083), charge (−37.9 mV), and loading efficiency (65.3%). Consequently, NPs consisting of PLGA and encapsulated DS coated with mPEG2k-PLGA at adjustable ratios were prepared using the DNP method. Formulations were then characterised, and their stability in horse serum was assessed. Results revealed the PEGylated DS-loaded PLGA nano-carriers to be more efficient; hence, in-vitro studies testing these formulations were subsequently performed using two distinct breast cancer cell lines, showing great potential to significantly enhance cancer therapy. Full article
(This article belongs to the Special Issue Nanoparticles in Drug Delivery Applications)
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