Nanoparticle-mediated Drug Delivery Research Articles

A comparative study of sericin and gluten for magnetic nanoparticle-mediated drug delivery to breast cancer cell lines

With breast cancer emerging as a pressing global health challenge, characterized by escalating incidence rates and geographical disparities, there is a critical need for innovative therapeutic strategies. This comprehensive research navigates the landscape of nanomedicine, specifically focusing on the potential of magnetic nanoparticles (MNPs), with magnetite (Fe3O4) taking center stage. MNPs, encapsulated in biocompatible polymers like silica known as magnetic silica nanoparticles (MSN), are augmented with phosphotungstate (PTA) for enhanced chemodynamic therapy (CDT). PTA is recognized for its dual role as a natural chelator and electron shuttle, expediting electron transfer from ferric (Fe3+) to ferrous (Fe2+) ions within nanoparticles. Additionally, protein-based charge-reversal nanocarriers like silk sericin and gluten are introduced to encapsulate (MSN-PTA) nanoparticles, offering a dynamic facet to drug delivery systems for potential revolutionization of breast cancer therapy. This study successfully formulates and characterizes protein-coated nanocapsules, specifically MSN-PTA-SER, and MSN-PTA-GLU, with optimal physicochemical attributes for drug delivery applications. The careful optimization of sericin and gluten concentrations results in finely tuned nanoparticles, showcasing uniform size, enhanced negative zeta potential, and remarkable stability. Various analyses, from Dynamic Light Scattering (DLS) and scanning electron microscopy (SEM) to transmission electron microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR), X-Ray diffraction analysis (XRD), and Thermogravimetric analysis (TGA), provide insights into structural integrity and surface modifications. Vibrating Sample Magnetometer (VSM) analysis underscores superparamagnetic behavior, positioning these nanocapsules as promising candidates for targeted drug delivery. In vitro evaluations demonstrate dose-dependent inhibition of cell viability in MCF-7 and Zr-75–1 breast cancer cells, emphasizing the therapeutic potential of MSN-PTA-SER and MSN-PTA-GLU. The interplay of surface charge and pH-dependent cellular uptake highlights the robust stability and versatility of these nanocarriers in tumor microenvironment, paving the way for advancements in targeted drug delivery and personalized nanomedicine. This comparative analysis explores the suitability of silk sericin and gluten, unraveling a promising avenue for the development of advanced, targeted, and efficient breast cancer treatments.

Bioinspired Adaptive Microdrugs Enhance the Chemotherapy of Malignant Glioma: Beyond Their Nanodrugs.

Solid nanoparticle-mediated drug delivery systems are usually confined to nanoscale due to the enhanced permeability and retention effect. However, they remain a great challenge for malignant glioma chemotherapy because of poor drug delivery efficiency and insufficient tumor penetration resulting from the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Inspired by biological microparticles (e.g., cells) with excellent adaptive deformation, it is demonstrated that the adaptive microdrugs (even up to 3.0µm in size) are more efficient than their nanodrugs (less than 200nm in size) to cross BBB/BBTB and penetrate into tumor tissues, achieving highly efficient chemotherapy of malignant glioma. The distinct delivery of the adaptive microdrugs is mainly attributed to the enhanced interfacial binding and endocytosis via adaptive deformation. As expected, the obtained adaptive microdrugs exhibit enhanced accumulation, deep penetration, and cellular internalization into tumor tissues in comparison with nanodrugs, significantly improving the survival rate of glioblastoma mice. It is believed that the bioinspired adaptive microdrugs enable them to efficiently cross physiological barriers and deeply penetrate tumor tissues for drug delivery, providing an avenue for the treatment of solid tumors.

Nanoparticle-Mediated Drug Delivery Systems for Precision Targeting in Oncology.

Nanotechnology has emerged as a transformative force in oncology, facilitating advancements in site-specific cancer therapy and personalized oncomedicine. The development of nanomedicines explicitly targeted to cancer cells represents a pivotal breakthrough, allowing the development of precise interventions. These cancer-cell-targeted nanomedicines operate within the intricate milieu of the tumour microenvironment, further enhancing their therapeutic efficacy. This comprehensive review provides a contemporary perspective on precision cancer medicine and underscores the critical role of nanotechnology in advancing site-specific cancer therapy and personalized oncomedicine. It explores the categorization of nanoparticle types, distinguishing between organic and inorganic variants, and examines their significance in the targeted delivery of anticancer drugs. Current insights into the strategies for developing actively targeted nanomedicines across various cancer types are also provided, thus addressing relevant challenges associated with drug delivery barriers. Promising future directions in personalized cancer nanomedicine approaches are delivered, emphasising the imperative for continued optimization of nanocarriers in precision cancer medicine. The discussion underscores translational research's need to enhance cancer patients' outcomes by refining nanocarrier technologies in nanotechnology-driven, site-specific cancer therapy.

Nanoparticle Mediated Drug Delivery Systems for Cancer Management

Nanoparticle Mediated Drug Delivery Systems for Cancer Management

Nanoparticle-Mediated Drug Delivery to Cervical Cells: Harnessing the Potential of Liposomes for Enhanced Therapeutic Efficacy

Cervical cancer continues to pose a substantial worldwide health obstacle, requiring novel treatment approaches. This research investigates the capacity of Nanoparticle-Mediated Drug Delivery to augment the efficacy of cervical cancer therapy. Highlighting the significance of precise medication delivery, using nanoparticles, namely liposomes, appears viable. Introducing a new method called Nanoparticle-Based Drug Delivery to Cervical Cells (NP-DD-CC) utilizes liposomes to accurately deliver medicinal substances while minimizing adverse effects on the whole body. The NP-DD-CC has remarkable characteristics, such as attaching nanocarriers to ligands to achieve target selectivity. The simulation findings provide diverse metrics for distinct Nanoparticle Densities: Localized Drug Concentration (67.76%), Reduction in Side Effects (48.5%), Overall Patient Tolerance Increase (40.4%), and Nanoparticle Retention Improvement (73%). NP-DD-CC presents a promising advancement in the treatment of cervical cancer by enhancing the accuracy of medication administration and reducing the occurrence of adverse side effects.

Precision cardiac targeting: empowering curcumin therapy through smart exosome-mediated drug delivery in myocardial infarction.

Nanoparticle-mediated drug delivery has emerged as a highly promising and effective therapeutic approach for addressing myocardial infarction. However, clinical translation tends to be a failure due to low cardiac retention as well as liver and spleen entrapment in previous therapies. Herein, we report a two-step exosome delivery system, which precludes internalization by the mononuclear phagocyte system before the delivery of therapeutic cardiac targeting exosomes (ExoCTP). Importantly, curcumin released by ExoCTP diminishes reactive oxygen species over-accumulation in ischemic myocardium, as well as serum levels of lactate dehydrogenase, malonyldialdehyde, superoxide dismutase and glutathione, indicating better antioxidant capacity than free curcumin. Finally, our strategy was proven to greatly potentiate the delivery and therapeutic efficacy of curcumin without systemic toxicity. Taken together, our smart exosome-mediated drug delivery strategy can serve either as therapeutics alone or in combination with other drugs for effective heart targeting and subsequent wound healing.

Directing cellular responses in a nanocomposite 3D matrix for tissue regeneration with nanoparticle-mediated drug delivery

Hydrogels play an important role in tissue engineering due to their native extracellular matrix-like characteristics, but they are insufficient in providing the necessary stimuli to support tissue formation. Efforts to integrate bioactive cues directly into hydrogels are hindered by incompatibility with hydrophobic drugs, issues of burst/uncontrolled release, and rapid degradation of the bioactive molecules. Skeletal muscle tissue repair requires internal stimuli and communication between cells for regeneration, and nanocomposite systems offer to improve the therapeutic effects in tissue regeneration. Here, the versatility of mesoporous silica nanoparticles (MSN) was leveraged to formulate a nanoparticle-hydrogel composite and to combine the benefits of controlled delivery of bioactive cues and cellular support. The tunable surface characteristics of MSNs were exploited to optimize homogeneity and intracellular drug delivery in a 3D matrix. Nanocomposite hydrogels formulated with acetylated or succinylated MSNs achieved high homogeneity in 3D distribution, with succinylated MSNs being rapidly internalized and acetylated MSNs exhibiting slower cellular uptake. MSN-hydrogel nanocomposites simultaneously allowed efficient local intracellular delivery of a hydrophobic model drug. To further study the efficiency of directing cell response, a Notch signaling inhibitor (DAPT) was incorporated into succinylated MSNs and incorporated into the hydrogel. MSN-hydrogel nanocomposites effectively downregulated the Notch signaling target genes, and accelerated and maintained the expression of myogenic markers. The current findings demonstrate a proof-of-concept in effective surface engineering strategies for MSN-based nanocomposites, suited for hydrophobic drug delivery in tissue regeneration with guided cues.

Nanodelivery systems: An efficient and target-specific approach for drug-resistant cancers.

Cancer treatment is still a global health challenge. Nowadays, chemotherapy is widely applied for treating cancer and reducing its burden. However, its application might be in accordance with various adverse effects by exposing the healthy tissues and multidrug resistance (MDR), leading to disease relapse or metastasis. In addition, due to tumor heterogeneity and the varied pharmacokinetic features of prescribed drugs, combination therapy has only shown modestly improved results in MDR malignancies. Nanotechnology has been explored as a potential tool for cancer treatment, due to the efficiency of nanoparticles to function as a vehicle for drug delivery. With this viewpoint, functionalized nanosystems have been investigated as a potential strategy to overcome drug resistance. This approach aims to improve the efficacy of anticancer medicines while decreasing their associated side effects through a range of mechanisms, such as bypassing drug efflux, controlling drug release, and disrupting metabolism. This review discusses the MDR mechanisms contributing to therapeutic failure, the most cutting-edge approaches used in nanomedicine to create and assess nanocarriers, and designed nanomedicine to counteract MDR with emphasis on recent developments, their potential, and limitations. Studies have shown that nanoparticle-mediated drug delivery confers distinct benefits over traditional pharmaceuticals, including improved biocompatibility, stability, permeability, retention effect, and targeting capabilities.

Cancer Nanomedicine: Emerging Strategies and Therapeutic Potentials.

Cancer continues to pose a severe threat to global health, making pursuing effective treatments more critical than ever. Traditional therapies, although pivotal in managing cancer, encounter considerable challenges, including drug resistance, poor drug solubility, and difficulties targeting tumors, specifically limiting their overall efficacy. Nanomedicine's application in cancer therapy signals a new epoch, distinguished by the improvement of the specificity, efficacy, and tolerability of cancer treatments. This review explores the mechanisms and advantages of nanoparticle-mediated drug delivery, highlighting passive and active targeting strategies. Furthermore, it explores the transformative potential of nanomedicine in tumor therapeutics, delving into its applications across various treatment modalities, including surgery, chemotherapy, immunotherapy, radiotherapy, photodynamic and photothermal therapy, gene therapy, as well as tumor diagnosis and imaging. Meanwhile, the outlook of nanomedicine in tumor therapeutics is discussed, emphasizing the need for addressing toxicity concerns, improving drug delivery strategies, enhancing carrier stability and controlled release, simplifying nano-design, and exploring novel manufacturing technologies. Overall, integrating nanomedicine in cancer treatment holds immense potential for revolutionizing cancer therapeutics and improving patient outcomes.

Non-Invasive, Targeted Nanoparticle-Mediated Drug Delivery across a Novel Human BBB Model.

The blood-brain barrier (BBB) is a highly sophisticated system with the ability to regulate compounds transporting through the barrier and reaching the central nervous system (CNS). The BBB protects the CNS from toxins and pathogens but can cause major issues when developing novel therapeutics to treat neurological disorders. PLGA nanoparticles have been developed to successfully encapsulate large hydrophilic compounds for drug delivery. Within this paper, we discuss the encapsulation of a model compound Fitc-dextran, a large molecular weight (70 kDa), hydrophilic compound, with over 60% encapsulation efficiency (EE) within a PLGA nanoparticle (NP). The NP surface was chemically modified with DAS peptide, a ligand that we designed which has an affinity for nicotinic receptors, specifically alpha 7 nicotinic receptors, found on the surface of brain endothelial cells. The attachment of DAS transports the NP across the BBB by receptor-mediated transcytosis (RMT). Assessment of the delivery efficacy of the DAS-conjugated Fitc-dextran-loaded PLGA NP was studied in vitro using our optimal triculture in vitro BBB model, which successfully replicates the in vivo BBB environment, producing high TEER (≥230 ) and high expression of ZO1 protein. Utilising our optimal BBB model, we successfully transported fourteen times the concentration of DAS-Fitc-dextran-PLGA NP compared to non-conjugated Fitc-dextran-PLGA NP. Our novel in vitro model is a viable method of high-throughput screening of potential therapeutic delivery systems to the CNS, such as our receptor-targeted DAS ligand-conjugated NP, whereby only lead therapeutic compounds will progress to in vivo studies.

Neuroblastoma: Emerging trends in pathogenesis, diagnosis, and therapeutic targets

Neuroblastoma (NB) accounts for about 13% of all pediatric cancer mortality and is the leading cause of pediatric cancer death for children aged 1 to 5 years. NB, a developmental malignancy of neural ganglia, originates from neural crest-derived cells, which undergo a defective sympathetic neuronal differentiation due to genomic and epigenetic aberrations. NB is a complex disease with remarkable biological and genetic variation and clinical heterogeneity, such as spontaneous regression, treatment resistance, and poor survival rates. Depending on its severity, NB is categorized as high-risk, intermediate-risk, and low-risk., whereas high-risk NB accounts for a high infant mortality rate. Several studies revealed that NB cells suppress immune cell activity through diverse signaling pathways, including exosome-based signaling pathways. Exosome signaling has been shown to modulate gene expression in the target immune cells and attenuate the signaling events through non-coding RNAs. Since high-risk NB is characterized by a low survival rate and high clinical heterogeneity with current intensive therapies, it is crucial to unravel the molecular events of pathogenesis and develop novel therapeutic targets in high-risk, relapsed, or recurrent tumors in NB to improve patient survival. This article discusses etiology, pathophysiology, risk assessment, molecular cytogenetics, and the contribution of extracellular vesicles, non-coding RNAs, and cancer stem cells in the tumorigenesis of NB. We also detail the latest developments in NB immunotherapy and nanoparticle-mediated drug delivery treatment options.

Impact of Nanoparticle Physicochemical Properties on Protein Corona and Macrophage Polarization.

Macrophages, the major component of the mononuclear phagocyte system, uptake and clear systemically administered nanoparticles (NPs). Therefore, leveraging macrophages as a druggable target may be advantageous to enhance NP-mediated drug delivery. Despite many studies focused on NP-cell interactions, NP-mediated macrophage polarization mechanisms are still poorly understood. This work aimed to explore the effect of NP physicochemical parameters (size and charge) on macrophage polarization. Upon exposure to biological fluids, proteins rapidly adsorb to NPs and form protein coronas. To this end, we hypothesized that NP protein coronas govern NP-macrophage interactions, uptake, and subsequent macrophage polarization. To test this hypothesis, model polystyrene NPs with various charges and sizes, as well as NPs relevant to drug delivery, were utilized. Data suggest that cationic NPs potentiate both M1 and M2 macrophage markers, while anionic NPs promote M1-to-M2 polarization. Additionally, anionic polystyrene nanoparticles (APNs) of 50 nm exhibit the greatest influence on M2 polarization. Proteomics was pursued to further understand the effect of NPs physicochemical parameters on protein corona, which revealed unique protein patterns based on NP charge and size. Several proteins impacting M1 and M2 macrophage polarization were identified within cationic polystyrene nanoparticles (CPNs) corona, while APNs corona included fewer M1 but more M2-promoting proteins. Nevertheless, size impacts protein corona abundance but not identities. Altogether, protein corona identities varied based on NP surface charge and correlated to dramatic differences in macrophage polarization. In contrast, NP size differentially impacts macrophage polarization, which is dominated by NP uptake level rather than protein corona. In this work, specific corona proteins were identified as a function of NP physicochemical properties. These proteins are correlated to specific macrophage polarization programs and may provide design principles for developing macrophage-mediated NP drug delivery systems.

Nanoparticle-Mediated Drug Delivery of Doxorubicin Induces a Differentiated Clonogenic Inactivation in 3D Tumor Spheroids In Vitro.

Involvement of 3D tumor cell models in the in vitro biological testing of novel nanotechnology-based strategies for cancer management can provide in-depth information on the real behavior of tumor cells in complex biomimetic architectures. Here, we used polyethylene glycol-encapsulated iron oxide nanoparticles for the controlled delivery of a doxorubicin chemotherapeutic substance (IONPDOX), and to enhance cytotoxicity of photon radiation therapy. The biological effects of nanoparticles and 150 kV X-rays were evaluated on both 2D and 3D cell models of normal human keratinocytes (HaCaT) and tumor cells-human cervical adenocarcinoma (HeLa) and human squamous carcinoma (FaDu)-through cell survival. In all 2D cell models, nanoparticles were similarly internalized in a peri-nuclear pattern, but resulted in different survival capabilities following radiation treatment. IONP on normal keratinocytes showed a protective effect, but a cytotoxic effect for cancer cells. In 3D tumor cell models, IONPDOX were able to penetrate the cell spheroids towards the hypoxic areas. However, IONPDOX and 150 kV X-rays led to a dose-modifying factor DMFSF=0.1 = 1.09 ± 0.1 (200 µg/mL IONPDOX) in HeLa spheroids, but to a radioprotective effect in FaDu spheroids. Results show that the proposed treatment is promising in the management of cervical adenocarcinoma.

Recent Advances in Mesoporous Silica Nanoparticle-Mediated Drug Delivery for Breast Cancer Treatment

Breast cancer (BC) currently occupies the second rank in cancer-related global female deaths. Although consistent awareness and improved diagnosis have reduced mortality in recent years, late diagnosis and resistant response still limit the therapeutic efficacy of chemotherapeutic drugs (CDs), leading to relapse with consequent invasion and metastasis. Treatment with CDs is indeed well-versed but it is badly curtailed with accompanying side effects and inadequacies of site-specific drug delivery. As a result, drug carriers ensuring stealth delivery and sustained drug release with improved pharmacokinetics and biodistribution are urgently needed. Core-shell mesoporous silica nanoparticles (MSNPs) have recently been a cornerstone in this context, attributed to their high surface area, low density, robust functionalization, high drug loading capacity, size-shape-controlled functioning, and homogeneous shell architecture, enabling stealth drug delivery. Recent interest in using MSNPs as drug delivery vehicles has been due to their functionalization and size-shape-driven versatilities. With such insights, this article focuses on the preparation methods and drug delivery mechanisms of MSNPs, before discussing their emerging utility in BC treatment. The information compiled herein could consolidate the database for using inorganic nanoparticles (NPs) as BC drug delivery vehicles in terms of design, application and resolving post-therapy complications.

Nanoparticles and convergence of artificial intelligence for targeted drug delivery for cancer therapy: Current progress and challenges.

Cancer is a life-threatening disease, resulting in nearly 10 million deaths worldwide. There are various causes of cancer, and the prognostic information varies in each patient because of unique molecular signatures in the human body. However, genetic heterogeneity occurs due to different cancer types and changes in the neoplasms, which complicates the diagnosis and treatment. Targeted drug delivery is considered a pivotal contributor to precision medicine for cancer treatments as this method helps deliver medication to patients by systematically increasing the drug concentration on the targeted body parts. In such cases, nanoparticle-mediated drug delivery and the integration of artificial intelligence (AI) can help bridge the gap and enhance localized drug delivery systems capable of biomarker sensing. Diagnostic assays using nanoparticles (NPs) enable biomarker identification by accumulating in the specific cancer sites and ensuring accurate drug delivery planning. Integrating NPs for cancer targeting and AI can help devise sophisticated systems that further classify cancer types and understand complex disease patterns. Advanced AI algorithms can also help in biomarker detection, predicting different NP interactions of the targeted drug, and evaluating drug efficacy. Considering the advantages of the convergence of NPs and AI for targeted drug delivery, there has been significantly limited research focusing on the specific research theme, with most of the research being proposed on AI and drug discovery. Thus, the study's primary objective is to highlight the recent advances in drug delivery using NPs, and their impact on personalized treatment plans for cancer patients. In addition, a focal point of the study is also to highlight how integrating AI, and NPs can help address some of the existing challenges in drug delivery by conducting a collective survey.

Global sensitivity analysis based on Gaussian-process metamodelling for complex biomechanical problems.

Biomechanical models often need to describe very complex systems, organs or diseases, and hence also include a large number of parameters. One of the attractive features of physics-based models is that in those models (most) parameters have a clear physical meaning. Nevertheless, the determination of these parameters is often very elaborate and costly and shows a large scatter within the population. Hence, it is essential to identify the most important parameters (worth the effort) for a particular problem at hand. In order to distinguish parameters which have a significant influence on a specific model output from non-influential parameters, we use sensitivity analysis, in particular the Sobol method as a global variance-based method. However, the Sobol method requires a large number of model evaluations, which is prohibitive for computationally expensive models. We therefore employ Gaussian processes as a metamodel for the underlying full model. Metamodelling introduces further uncertainty, which we also quantify. We demonstrate the approach by applying it to two different problems: nanoparticle-mediated drug delivery in a complex, multiphase tumour-growth model, and arterial growth and remodelling. Even relatively small numbers of evaluations of the full model suffice to identify the influential parameters in both cases and to separate them from non-influential parameters. The approach also allows the quantification of higher-order interaction effects. We thus show that a variance-based global sensitivity analysis is feasible for complex, computationally expensive biomechanical models. Different aspects of sensitivity analysis are covered including a transparent declaration of the uncertainties involved in the estimation process. Such a global sensitivity analysis not only helps to massively reduce costs for experimental determination of parameters but is also highly beneficial for inverse analysis of such complex models.

Meet the First Authors.

Meet the First Authors.

Folate ‐ Conjugated Magnetite Nanoparticles for Targeted Drug Delivery and Hyperthermia Applications

AbstractResearch in magnetic nanoparticles mediated drug delivery system for cancer therapy is of current demand due to its various attributes. It provides a way for ease of stimuli responsive drug delivery and also act as a hyperthermic agent. Folic acid is extensively used for functionalisation of nanoparticles (NP) as various cancerous cells show overexpression of folate receptors. In this article, we report folic acid conjugated magnetite (Fe3O4) NP by two different ways and characterised by XRD, SEM, UV, FTIR and Raman spectroscopy. The folic acid was conjugated by its amine and carboxyl groups respectively on the magnetite NP to bestow them with targeting abilities. The NP formed are spherical and the size ranges from 32–100 nm and are highly aqueous dispersible as evidenced through the wettability studies. The blank NP shows some cytotoxicity on the MCF‐7 breast cancer cells probably due to oxidative stress. The NP shows high DOX loading efficiency due to higher surface area and negative surface charge. The superior magnetic properties of the NP assures hyperthermic temperature of 41 °C within 49 sec for 2 mg/ml NP concentration at an applied current of 273 A and frequency 316 kHz.

Targeted Diagnosis, Therapeutic Monitoring, and Assessment of Atherosclerosis Based on Mesoporous Silica Nanoparticles Coated with cRGD-Platelets.

Objective The off-target effects and severe side effects of PPARα and LXRα agonists greatly limit their application in atherosclerosis (AS). Therefore, this study intended to use mesoporous silica nanoparticles as carriers to generate MnO nanoparticles in situ with T1WI-MRI in mesoporous pores and simultaneously load PPARα and LXRα agonists. Afterward, cRGD-chelated platelet membranes can be used for coating to construct a new nanotheranostic agent. Methods cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were synthesized by a chemical method. Dynamic light scattering (DLS) was utilized to detect the size distribution and polydispersity index (PDI) of the nanoparticles. The safety of the nanoparticles was detected by CCK8 in vitro and HE staining and kidney function in vivo. Cell apoptosis was detected by flow cytometry detection and TUNEL staining. Oxidative stress responses (ROS, SOD, MDA, and NOX levels) were tested via a DCFH-DA assay and commercial kits. Immunofluorescence and phagocytosis experiments were used to detect the targeting of nanoparticles. Magnetic resonance imaging (MRI) was used to detect the imaging performance of cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles. Using western blotting, the expression changes in LXRα and ABCA1 were identified. Results cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles were successfully established, with a particle size of approximately 150 nm and PDI less than 0.3, and showed high safety both in vitro and in vivo. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed good targeting properties and better MRI imaging performance in AS. cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles showed better antioxidative capacities, MRI imaging performance, and diagnostic and therapeutic effects on AS by regulating the expression of LXRα and ABCA1. Conclusion In the present study, cRGD-platelet@MnO/MSN@PPARα/LXRα nanoparticles with high safety and the capacity to target vulnerable plaques of AS were successfully established. They showed better performance on MRI images and treatment effects on AS by promoting cholesterol efflux through the regulation of ABCA1. These findings might address the problems of off-target effects and side effects of nanoparticle-mediated drug delivery, which will enhance the efficiency of AS treatment and provide new ideas for the clinical treatment of AS.

Functionalization strategies of polymeric nanoparticles for drug delivery in Alzheimer's disease: Current trends and future perspectives.

Alzheimer’s disease (AD), the most common form of dementia, is a progressive and multifactorial neurodegenerative disorder whose primary causes are mostly unknown. Due to the increase in life expectancy of world population, including developing countries, AD, whose incidence rises dramatically with age, is at the forefront among neurodegenerative diseases. Moreover, a definitive cure is not yet within reach, imposing substantial medical and public health burdens at every latitude. Therefore, the effort to devise novel and effective therapeutic strategies is still of paramount importance. Genetic, functional, structural and biochemical studies all indicate that new and efficacious drug delivery strategies interfere at different levels with various cellular and molecular targets. Over the last few decades, therapeutic development of nanomedicine at preclinical stage has shown to progress at a fast pace, thus paving the way for its potential impact on human health in improving prevention, diagnosis, and treatment of age-related neurodegenerative disorders, including AD. Clinical translation of nano-based therapeutics, despite current limitations, may present important advantages and innovation to be exploited in the neuroscience field as well. In this state-of-the-art review article, we present the most promising applications of polymeric nanoparticle-mediated drug delivery for bypassing the blood-brain barrier of AD preclinical models and boost pharmacological safety and efficacy. In particular, novel strategic chemical functionalization of polymeric nanocarriers that could be successfully employed for treating AD are thoroughly described. Emphasis is also placed on nanotheranostics as both potential therapeutic and diagnostic tool for targeted treatments. Our review highlights the emerging role of nanomedicine in the management of AD, providing the readers with an overview of the nanostrategies currently available to develop future therapeutic applications against this chronic neurodegenerative disease.