Nanoscale Drug Delivery Systems Research Articles

The involvement and application potential of exosomes in breast cancer immunotherapy

Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.

Leprosy: Comprehensive insights into pathology, immunology, and cutting-edge treatment strategies, integrating nanoparticles and ethnomedicinal plants

Mycobacterium leprae is the causative agent responsible for the chronic disease known as leprosy. This condition is characterized by dermal involvement, often leading to peripheral nerve damage, sensory-motor loss, and related abnormalities. Both innate and acquired immunological responses play a role in the disease, and even in individuals with lepromatous leprosy, there can be a transient increase in T cell immunity during lepromatous reactions. Diagnosing of early-stage leprosy poses significant challenges. In this context, nanoparticles have emerged as a promising avenue for addressing various crucial issues related to leprosy. These include combatting drug resistance, mitigating adverse effects of conventional medications, and enhancing targeted drug delivery. This review serves as a comprehensive compilation, encompassing aspects of pathology, immunology, and adverse effects of multidrug delivery systems in the context of leprosy treatment. Furthermore, the review underscores the significance of ethnomedicinal plants, bioactive secondary metabolites, and nanotherapeutics in the management of leprosy. It emphasizes the potential to bridge the gap between existing literature and ongoing research efforts, with a profound scope for validating traditional claims, developing herbal medicines, and formulating nanoscale drug delivery systems that are safe, effective, and widely accepted.

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs.

This manuscript offers a comprehensive overview of nanotechnology's impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.

Microfluidic development of brain-derived neurotrophic factor loaded solid lipid nanoparticles: An in vitro evaluation in the post-traumatic brain injury neuroinflammation model

Microfluidic-based nanoscale drug delivery systems have risen to prominence in the field of precision nanomedicine in recent years. This intriguing innovation could provide unique therapeutic prospects in the treatment of serious disorders as traumatic brain injury, a potentially fatal condition that is widespread during childhood. According to current scientific study, neurotrophins are vital for the healing of injured brain parenchyma, and the brain-derived neurotrophic factor (BDNF) in particular may have significant regenerative effects. To address BDNF-related pharmacokinetic constraints, microfluidic-assisted manufacturing of BDNF-loaded solid lipid nanoparticles (BDNF-SLNs) was carried out, and following evaluation, the formulation demonstrated optimum characteristics in terms of size (190.3 ± 10.1 nm), PDI (0.180 ± 0.023), and ζ-potential (– 39.2 ± 1.30 mV). Short-term stability studies and the haemolysis assay verified the formulation's biocompatibility, while an in vitro permeability analysis revealed an increase in the Papp of the encapsulated BDNF (1.27x10−5 cm/s) as compared to plain BDNF (9.31x10−6 cm/s). The in vitro mimicked neuroinflammatory model demonstrated an enhanced decrease in nitrite production and Nos mRNA levels using BDNF-SLNs compared to plain BDNF as a control, validating the proficiency of the microfluidic-based drug delivery systems as pioneering and valuable approaches for the brain delivery of biologicals.

Rational design of a nonclassical liposomal nanoscale drug delivery system for innovative cancer therapy

AbstractAdvanced drug delivery systems are widely considered to be powerful approaches for treating cancer and many other diseases because of their superior ability to improve pharmacokinetics, promote lesion‐targeted delivery efficacy, and/or reduce the toxic effects of diverse therapeutics. Owing to the unique biomimetic structure of lipid bilayers surrounding aqueous cavities, liposomes have been found to encapsulate various therapeutics, ranging from small molecules with different hydrophobicities to biomacromolecules. With the advent of surface PEGylation, stealth liposomes with excellent in vivo long‐circulating behaviors have been generated, thus these liposomes have been extensively explored for the development of liposomal drugs with greatly improved in vivo pharmacokinetic behaviors by functioning as delivery vehicles. Inspired by their successes in clinical practice, stealth liposomes have recently been utilized as the main building scaffold or surface coating layers of other nanoparticulate formulations, which are coined as nonclassical liposomal nanoscale drug delivery systems (NDDSs) in this review, to enable the rational design of next‐generation liposomal nanomedicine. Therefore, after overviewing the latest progress in the development of conventional liposome‐based nanomedicine, we will introduce the development of these nonclassical liposomal NDDSs as well as their innovative cancer treatment strategies. We will subsequently provide a critical perspective on the future development of new cancer nanomedicines based on these rationally designed nonclassical liposomal NDDSs.

Monitoring the Degradation of Metal‐Organic Framework Drug Nanocarriers by In‐situ NMR Spectroscopy

An accurate characterization methodology is indispensable to design nanoparticle‐based drug delivery system (DDS) adapted to specific diseases and therapies. However, characterization techniques employed to investigate drug release and nanoparticle degradation require separating the nanoparticles from their suspension media, which can lead to artefacts. Therefore, there is a clear need to implement novel versatile in‐situ methods. Here, we report the use of in‐situ NMR spectroscopy to monitor drug delivery processes from MOF nanocarriers, both in solution and in the solid state simultaneously. In‐situ1H NMR investigation of nanoMIL‐100(Al) suspension in phosphate medium enabled recording the trimesate ligand loss in the solid phase and the ligand release in the liquid phase as a function of time. Simultaneously, 27Al NMR enabled assessing the progressive replacement of carboxylate ligands by phosphates leading to the formation of new aluminum species. Using the same strategy, we also compared the degradation of nanoMIL‐100(Al) loaded with two drug analogs, highlighting an effect of metal‐ligand complexing strength. Furthermore, our in‐situ technique is applicable to studying the reaction of paramagnetic nanoMIL‐100(Fe) in the liquid phase. This work offers an alternative to ex‐situ techniques for understanding the degradation mechanism of MOF nanocarriers and could be an asset for other nanoscale DDSs.

Photo-responsive doxorubicin delivery: Nanogel systems based on azobenzene and host-guest interactions enhanced by squeezing action

Conventional chemotherapy methods impact both normal and cancerous cells; therefore, it is essential to design drug delivery systems to reduce undesired drug effects. Nano-scaled drug delivery systems have the advantage of high retention time in blood as well as the capability of conventional penetration into tissue barriers. In this study, light-sensitive biocompatible nanogels with a core-shell structure have been synthesized and characterized as drug delivery system loaded with doxorubicin (DOX). These smart nanogels possess a hydrophobic core, coated with hydrophilic starch polymeric chains, which are modified with β-cyclodextrin (βCD). The core-shell formation is based on host-guest interaction between azobenzene rings as photochromic agents and βCD hydrophobic cavities. The mechanism of drug release is based on the cis-trans isomerization of azobenzene molecules upon light irradiation and dissociation of crore-shell entities. Due to this isomerization, shrinkage of hydrophobic core and removal of shell occurred simultaneously, which assist the drug release. In conclusion, a nanoscale carrier was designed with sustainable drug release under light irradiation as an external and non-contact stimulus. The synthesized nanogels were characterized by FT-IR, 1H NMR, SEM, DLS, and TEM. In addition, the MTT assay proposed that the viability of the A-431 cells has plunged in the presence irradiated nanogels, also histological studies were performed to evaluate the efficacy of the prepared nanogels in cancerous tissues.

Nanogels Based on N,N-Dimethylacrylamide and β-Cyclodextrin Triacrylate for Enhanced Solubility and Therapeutic Efficacy of Aripiprazole.

Aripiprazole (ARZ) is a medication used for the treatment of various diseases such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette's syndrome. Despite its therapeutic benefits, ARZ is characterized by a poor water solubility which provoked the development of various delivery systems in order to enhance its solubility. In the present work, a nanoscale drug delivery system based on N,N-dimethylacrylamide (DMAA) and β-cyclodextrin triacrylate (β-CD-Ac3) as potential aripiprazole delivery vehicles was developed. The nanogels were synthesized by free radical polymerization of DMAA in the presence of β-CD-Ac3 as a crosslinking agent and then loaded with ARZ via host-guest inclusion complexation. The blank- and drug-loaded nanogels were evaluated using different methods. Fourier transform infrared (FTIR) spectroscopy was employed to confirm the incorporation of β-CD moieties into the polymer network. Dynamic light scattering (DLS) was used to study the size of the developed systems. The samples exhibited a monomodal particle size distribution and a relatively narrow dispersity index. The hydrodynamic diameter (Dh) of the gels varied between 107 and 129 nm, with a tendency for slightly larger particles as the β-CD-Ac3 fraction increased. Loading the drug into the nanocarrier resulted in slightly larger particles than the blank gels, but their size was still in the nanoscopic range (166 to 169 nm). The release profiles in PBS were studied and a sustained release pattern with no significant burst effect was observed. A cytotoxicity assessment was also conducted to demonstrate the non-toxicity and biocompatibility of the studied polymers.

Morusin-Cu(II)-indocyanine green nanoassembly ignites mitochondrial dysfunction for chemo-photothermal tumor therapy

Nanoscale drug delivery systems derived from natural bioactive materials accelerate the innovation and evolution of cancer treatment modalities. Morusin (Mor) is a prenylated flavonoid compound with high cancer chemoprevention activity, however, the poor water solubility, low active pharmaceutical ingredient (API) loading content, and instability compromise its bioavailability and therapeutic effectiveness. Herein, a full-API carrier-free nanoparticle is developed based on the self-assembly of indocyanine green (ICG), copper ions (Cu2+) and Mor, termed as IMCNs, via coordination-driven and π-π stacking for synergistic tumor therapy. The IMCNs exhibits a desirable loading content of Mor (58.7 %) and pH/glutathione (GSH)-responsive motif. Moreover, the photothermal stability and photo-heat conversion efficiency (42.8 %) of IMCNs are improved after coordination with Cu2+ and help to achieve photothermal therapy. Afterward, the released Cu2+ depletes intracellular overexpressed GSH and mediates Fenton-like reactions, and further synergizes with ICG at high temperatures to expand oxidative damage. Furthermore, the released Mor elicits cytoplasmic vacuolation, expedites mitochondrial dysfunction, and exerts chemo-photothermal therapy after being combined with ICG to suppress the migration of residual live tumor cells. In vivo experiments demonstrate that IMCNs under laser irradiation could excellently inhibit tumor growth (89.6 %) through the multi-modal therapeutic performance of self-enhanced chemotherapy/coordinated-drugs/ photothermal therapy (PTT), presenting a great potential for cancer therapy.

Observation of antitumor mechanism of GE11-modified paclitaxel and curcumin liposomes based on cellular morphology changes

Curcumin and paclitaxel are widely used as anti-tumor hydrophobic model drugs for the designation of smart tumor-targeting nanocarriers and the study of the correlation between structural characteristics of nanoparticles and in vivo therapeutic efficacy. Various signaling pathways on cell growth and proliferation have been comprehensively studied in vitro and in vivo under the action of curcumin and paclitaxel nanoparticles. In this paper, we prepared EGFR-targeted GE11 peptide-modified curcumin and paclitaxel compound liposomes (CUR-PTX@GE11-L). The tumor suppression mechanism of CUR-PTX@GE11-L is observed from the aspects of drug release behavior, changes of cell morphology, liver retention, and tumor-targeting efficiency. We hope it can provide a new vision for the rational construction of smart nanoscale drug delivery system through the observation of cytotoxic effects of CUR-PTX@GE11-L, especially on the cellular morphology change.Graphical

Core-Shell Nanoparticles for Pulmonary Drug Delivery.

Nanoscale drug delivery systems have provoked interest for application in various therapies on account of their ability to elevate the intracellular concentration of drugs inside target cells, which leads to an increase in efficacy, a decrease in dose, and dose-associated adverse effects. There are several types of nanoparticles available; however, core-shell nanoparticles outperform bare nanoparticles in terms of their reduced cytotoxicity, high dispersibility and biocompatibility, and improved conjugation with drugs and biomolecules because of better surface characteristics. These nanoparticulate drug delivery systems are used for targeting a number of organs, such as the colon, brain, lung, etc. Pulmonary administration of medicines is a more appealing method as it is a noninvasive route for systemic and locally acting drugs as the pulmonary region has a wide surface area, delicate blood-alveolar barrier, and significant vascularization. A core-shell nano-particulate drug delivery system is more effective in the treatment of various pulmonary disorders. Thus, this review has discussed the potential of several types of core-shell nanoparticles in treating various diseases and synthesis methods of core-shell nanoparticles. The methods for synthesis of core-shell nanoparticles include solid phase reaction, liquid phase reaction, gas phase reaction, mechanical mixing, microwave- assisted synthesis, sono-synthesis, and non-thermal plasma technology. The basic types of core-shell nanoparticles are metallic, magnetic, polymeric, silica, upconversion, and carbon nanomaterial- based core-shell nanoparticles. With this special platform, it is possible to integrate the benefits of both core and shell materials, such as strong serum stability, effective drug loading, adjustable particle size, and immunocompatibility.

Harnessing Nanotechnology for Optimized Herbal Cancer Treatment: A Comprehensive Review of Nanoscale Drug Delivery Systems

Cancer is widely recognized as the second leading cause of death on a global scale. In recent years, nanotechnology has emerged as a promising strategy in the field of cancer therapy. Nanoscale drug delivery systems, a category of innovative technologies, harness the potential of various nanoparticles and nanomaterials to efficiently transport chemotherapeutic drugs, revolutionizing cancer treatment. The use of natural products has shown substantial promise in both the prevention and therapy of cancer. Herbal medicines, in particular, have gained widespread use due to their inherent therapeutic advantages and notably fewer adverse effects compared to modern drugs. However, their hydrophobic nature has presented a challenge, limiting their bioavailability and therapeutic efficacy. To overcome these limitations, researchers have developed nanocarriers tailored for the delivery of therapeutic agents to specific target cells. The combination of nanocarriers with herbal remedies results in improved bioavailability, enhanced pharmacological activity, and increased stability, all while minimizing systemic toxicity in cancer treatment. This review provides a comprehensive discussion of novel nanocarriers that find application in cancer treatment, with a specific focus on herbal medicine. The amalgamation of these innovative approaches offers promising prospects for the future of cancer therapy.

Characterization of electrospun pluronic F68/polyvinyl alcohol nanofibers composites containing titanium dioxide, silver, and cobalt nanoparticles for biomedical applications

Nanoscale drug delivery systems and biomedical sensors are witnessing huge research interests. Polymeric nanoparticles, nanofibers, liposomes, and nano-emulsion are regarded as novel sensors and drug delivery systems including the various types of wound dressings formulated by micro/nanofibers, hydrogels, hydrocolloids, films, foams, and sponges. Consequently, the electro-spun nanofibrous mats received the most attention since the drugs and nanoparticles embedded nanofibers have been recognized as the potential candidates for sensors and wound dressing applications. These composite materials have superior surface area-to-volume ratio, high nano-porosity, distinct skin extracellular matrix structure, and ease of electro-spinning, which also supports a prolonged drug release. In this study the main advantages of the nano-fibrillary network and the active substances that can be incorporated in fabricating the composite nanofibers as sensors and wound dressing materials are discussed. The promising “Pluronic F68” and polyvinyl alcohol (PVA), materials are used including nanoparticles (NPs) of titanium dioxide (TiO2), silver, and cobalt. The difficulties that arise by converting the Pluronic into nanofibers via electrospinning due to its low melting point and beads formation and the blending of this material with polyvinyl alcohol (PVA) are discussed. The electro-spinability of the pure Pluronic, PVA and their blends are evaluated. The microstructures and morphologies of the fabricated composite nanofibers and structures are characterized using scanning electron microscopy (SEM), thermogravimetric analysis (TGA), differential thermal analysis (DSC), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). The fabricated blended nanofibers were found to be compact and entangled having a diameter from 50 nm to 80 nm and length ranging from 1 to 3 μm. Meanwhile, the pure Pluronic produced nano-beads with an average size of 40 nm. These nanocomposites can be used in biomedical applications such as biosensors by embedding nanoparticles of TiO2, silver, and cobalt and for antibacterial treatment in woundcare dressings.

Long-term shelf-life liposomes for delivery of prednisolone and budesonide

Liposomes are nanoscale drug delivery systems built up from lipid layers and are able to spontaneously self-assemble in an aqueous environment. Both hydrophilic and hydrophobic drugs can be delivered by liposomes and this kind of nanoformulation offers many advantages regarding biodistribution, drug absorption and controlled drug release. Corticosteroids as lipophilic molecules are able to integrate into the lipid bilayer. This novel approach can improve the efficacy of several anti-inflammatory, such as asthma therapy.Our aim was to create liposomes with long shelf-life, which can incorporate and release corticosteroids such as Prednisolone (Pred) and Budesonide (Bud) at the temperature of inflamed tissues. Two kinds of liposome samples were prepared from three different kinds of phospholipids to get unilamellar vesicles with 100 nm in diameter and characterize their physicochemical properties and effect on living cells. Their main phase transition temperature in the physiologically relevant temperature range was measured by differential scanning calorimetry. According to the size distributions determined by dynamic light scattering, all drug-containing liposomes were stable for 6 months. All of the liposome types have a slightly negative zeta potential value. The Fourier-transform infrared spectroscopy revealed no chemical interaction between the drug and lipid molecules. The entrapment efficacy was determined by size-exclusion gel chromatography combined with UV–VIS spectrophotometry and it was very high in both cases (between 70 and 87%). The drug leakage was 35–40% for Pred and 6–8% for Bud in the first 30 min. The effect of liposomal drugs on cell viability was measured on the EBC-1 human lung carcinoma cell line. Neither the free corticosteroids nor their liposomal form were toxic to the cells. The cellular internalization of the liposomes was proved by flow cytometry and confocal microscopy.In summary, these liposomes could be useful in the delivery of corticosteroids (Pred or particularly Bud) in more effective asthma therapy, having fewer side effects due to the nanoformulation.

Chitosan/alginate nanogel potentiate berberine uptake and enhance oxidative stress mediated apoptotic cell death in HepG2 cells

Biopolymer-based nanoscale drug delivery systems have become a promising approach to overcome the limitations associated with conventional chemotherapeutics used for cancer treatment. Herein, we reported to develop a hydrophilic nanogel (NG) composed of Chitosan (Chi) and sodium alginate (Alg) using the ion gelation method for delivering Berberine hydrochloride (BBR), an alkaloid obtained from Berberis aristata roots. The use of different nanocarriers for BBR delivery has been reported previously, but the bioavailability of these carriers was limited due to phagocytic uptake and poor systemic delivery. The developed NG showed enhanced stability and efficient entrapment of BBR ∼92 %, resulting in a significant increase in bioavailability. The pH-dependent release behavior demonstrated sustained and effective release of ∼86 %, ∼74 % and, ∼53 % BBR at pH 5.5, 6.6, and 7.4 respectively after 72h, indicating its potential as a drug carrier. Additionally, the cellular uptake of BBR was significantly higher ∼19 % in the BBR-NG (25 μM) than in bulk BBR (100 μM), leading to enhanced ROS generation, mitochondrial depolarisation, and inhibition of cell proliferation and colony formation in HepG2 cells. In summary, the results suggest that the Chi/Alg biopolymer-based nano-formulation could be an effective approach for delivering BBR and enhancing its cellular uptake, efficacy, and cytotoxicity.

Nano-Based Drug Delivery Systems: Potential Developments in the Therapy of Metastatic Osteosarcoma-A Narrative Review.

Osteosarcoma, a predominant malignant bone tumor, poses significant challenges due to its high metastatic and recurrent nature. Although various therapeutic strategies are currently in use, they often inadequately target osteosarcoma metastasis. This review focuses on the potential of nanoscale drug delivery systems to bridge this clinical gap. It begins with an overview of the molecular mechanisms underlying metastatic osteosarcoma, highlighting the limitations of existing treatments. The review then transitions to an in-depth examination of nanoscale drug delivery technologies, emphasizing their potential to enhance drug bioavailability and reduce systemic toxicity. Central to this review is a discussion of recent advancements in utilizing nanotechnology for the potential intervention of metastatic osteosarcoma, with a critical analysis of several preclinical studies. This review aims to provide insights into the potential applications of nanotechnology in metastatic osteosarcoma therapy, setting the stage for future clinical breakthroughs and innovative cancer treatments.

Modern Photodynamic Glioblastoma Therapy Using Curcumin- or Parietin-Loaded Lipid Nanoparticles in a CAM Model Study.

Natural photosensitizers, such as curcumin or parietin, play a vital role in photodynamic therapy (PDT), causing a light-mediated reaction that kills cancer cells. PDT is a promising treatment option for glioblastoma, especially when combined with nanoscale drug delivery systems. The curcumin- or parietin-loaded lipid nanoparticles were prepared via dual asymmetric centrifugation and subsequently characterized through physicochemical analyses including dynamic light scattering, laser Doppler velocimetry, and atomic force microscopy. The combination of PDT and lipid nanoparticles has been evaluated in vitro regarding uptake, safety, and efficacy. The extensive and well-vascularized chorioallantois membrane (CAM) of fertilized hen's eggs offers an optimal platform for three-dimensional cell culture, which has been used in this study to evaluate the photodynamic efficacy of lipid nanoparticles against glioblastoma cells. In contrast to other animal models, the CAM model lacks a mature immune system in an early stage, facilitating the growth of xenografts without rejection. Treatment of xenografted U87 glioblastoma cells on CAM was performed to assess the effects on tumor viability, growth, and angiogenesis. The xenografts and the surrounding blood vessels were targeted through topical application, and the effects of photodynamic therapy have been confirmed microscopically and via positron emission tomography and X-ray computed tomography. Finally, the excised xenografts embedded in the CAM were analyzed histologically by hematoxylin and eosin and KI67 staining.

Elasticity, an often-overseen parameter in the development of nanoscale drug delivery systems.

Nanoparticles have shown an enormous potential as drug delivery systems in the lab. However, translation to the clinics or even market approval often fails. So far, the reason for this discrepancy is manifold. Physicochemical properties such as size, surface potential, and surface chemistry are in focus of research for many years. Other equally important parameters, influencing whether a successful drug delivery can be achieved, are mechanical properties of nanoparticles. Even though this is often not even considered during formulation development, and it is not requested for approval, an increasing number of studies show that it is important to have knowledge about these characteristics. In this article, we discuss examples highlighting the influence of elasticity in nanoscale biological interactions focusing on mucosal delivery and on tumor targeting. Besides this, we discuss the influence of different measurement settings using atomic force microscopy for the determination of mechanical properties of drug carriers.

An infection-microenvironment-targeted and responsive peptide-drug nanosystem for sepsis emergency by suppressing infection and inflammation

Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation. Nevertheless, current therapeutic regimens are inadequate to promptly address the vast diversity of potential pathogens. Omiganan, an antimicrobial peptide, has shown promise for neutralizing endotoxins and eliminating diverse pathogens. However, its clinical application is hindered by safety and stability concerns. Herein, we present a nanoscale drug delivery system (Omi-hyd-Dex@HA NPs) that selectively targets infectious microenvironments (IMEs) and responds to specific stimuli for efficient intervention in sepsis. The system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid (HA). The HA coating not only facilitates IMEs-targeting through interaction with intercellular-adhesion-molecule-1 on inflamed endotheliocytes, but also improves the biosafety of the nanosystem and enhances drug accumulation in primary infection sites triggered by hyaluronidase. The nanoparticles release dual drugs in IMEs through pH-sensitive cleavage of hydrazone bonds to eradicate pathogens and suppress inflammation. In multiple tissue infection and sepsis animal models, Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction, thereby preventing subsequent fatal complications and significantly improving survival outcomes. The bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies.

Co-delivery of dimeric camptothecin and chlorin e6 via polypeptide-based micelles for chemo-photodynamic synergistic therapy

BackgroundThe integration of photodynamic therapy with a chemical drug-delivery system has displayed great potential in enhancing anticancer therapy. However, the solubility and non-specific biodistribution of both chemotherapeutic agents and photosensitizers continue to pose challenges that hinder their clinical applications.MethodA polypeptide-based nanoscale drug delivery system was fabricated to address the prementioned issues. An amphiphilic polymer was formed by conjugating the photosensitizer chlorin e6 (Ce6) onto a polypeptide poly-(L-lysine)-b-polyphenylalanine (PKF) for encapsulating the model drug dimeric camptothecin (DCPT), and the nanoparticles (PCD) with high drug loading efficiency were further modified with acid-sensitive polyethylene glycol (PEG) to yield the drug delivery sytem (PPCD).ResultsThe DCPT and Ce6 encapsulation efficiency were analyzed as 99% and 73.5%, respectively. In phosphate-buffered saline (PBS) solution at a pH of 7.4, the PEG shell improved the stability of micelles and shielded their positive charge while in the acidic tumor microenvironment, the pH-sensitive PEG layer was removed to expose the cationic nanoparticles, thus facilitating the cellular uptake of PPCD micelles. Benefiting from the enhanced cellular internalization, the amount of intracellular reactive oxygen species (ROS) treated with PCD and PPCD micelles were obviously increased. Furthermore, the enhanced anti-cancer efficacy prompted by PPCD micelles was validated through cellular and animal study.ConclusionThis study presents a promising method to promote the solubility and biodistribution of both chemotherapeutic agent and photosensitizer, thereby facilitating the further application of chemo-photodynamic cancer therapy.Graphical