Tumor-associated macrophages (TAMs) constitute the largest number of immune cells in the tumor microenvironment (TME). They play an essential role in promoting tumor progression and metastasis, which makes them a potential therapeutic target for cancer treatment. TAMs are usually divided into two categories: pro-tumoral M2-like TAMs and antitumoral M1 phenotypes at either extreme. The reprogramming of M2-like TAMs toward a tumoricidal M1 phenotype is of particular interest for the restoration of antitumor immunity in cancer immunotherapy. Notably, nanomedicines have shown great potential for cancer therapy due to their unique structures and properties. This review will briefly describe the biological features and roles of TAMs in tumor, and then discuss recent advances in nanomedicine-mediated repolarization of TAMs for cancer immunotherapy. Finally, perspectives on nanomedicine-mediated repolarization of TAMs for effective cancer immunotherapy are also presented.

The adoptive transfer of T cells redirected by chimeric antigen receptors (CARs) has made a dramatic breakthrough in defeating hematological malignancies. However, in solid tumor treatment, CAR-T-cell therapy has attained limited therapeutic benefits due to insufficient infiltration and expansion, rapidly diminishing function following adoptive transfer, and severe life-threatening toxicities. To address these challenges, advancements in nanotechnology have utilized innovative approaches to devise stronger CAR-T cells with reduced toxicity and enhanced anti-tumor activity. Equipping CAR-T cells with multifunctional nanoparticles can abrogate immunosuppressive signaling in the tumor area, augment the functions of CAR-T cells, and mitigate their toxicity against normal tissues. Additionally, nanoparticle-mediated CAR-T-cell programming has the potential to optimize manufacturing and lower the cost for the broader implementation of CAR-T-cell therapy. In this review, we introduce the obstacles to be surmounted in CAR-T-cell therapy, highlight the nanotechnology-based strategies that aim to enrich the therapeutic applications of CAR-T-cell therapy, and envision the prospect of nanoparticle-assisted CAR-T-cell therapy.

Inflammatory bowel disease (IBD) is a complex and recurring inflammatory disorder that affects the gastrointestinal tract and is influenced by genetic predisposition, immune dysregulation, the gut microbiota, and environmental factors. Advanced therapies, such as biologics and small molecules, target diverse immune pathways to manage IBD. Nanoparticle (NP)-based drugs have emerged as effective tools, offering controlled drug release and targeted delivery. This review highlights NP modifications for anti-inflammatory purposes, utilizing changes such as those in size, charge, redox reactions, and ligand-receptor interactions in drug delivery systems. By using pathological and microenvironmental cues to guide NP design, precise targeting can be achieved. In IBD, a crucial aspect of NP intervention is targeting specific types of cells, such as immune and epithelial cells, to address compromised intestinal barrier function and reduce overactive immune responses. This review also addresses current challenges and future prospects, with the goal of advancing the development of NP-mediated strategies for IBD treatment.

Extracellular vesicles (EVs), nanosized lipid bilayer vesicles released by nearly all types of cells, play pivotal roles as intercellular signaling mediators with diverse biological activities. Their adaptability has attracted interest in exploring their role as disease biomarker theranostics. However, the in vivo biodistribution and pharmacokinetic profiles of EVs, particularly following administration into living subjects, remain unclear. Thus, in vivo imaging is vital to enhance our understanding of the homing and retention patterns, blood and tissue half-life, and excretion pathways of exogenous EVs, thereby advancing real-time monitoring within biological systems and their therapeutic applications. This review examines state-of-the-art methods including EV labeling with various agents, including optical imaging, magnetic resonance imaging, and nuclear imaging. The strengths and weaknesses of each technique are comprehensively explored, emphasizing their clinical translation. Despite the potential of EVs as cancer theranostics, achieving a thorough understanding of their in vivo behavior is challenging. This review highlights the urgency of addressing current questions in the biology and therapeutic applications of EVs. It underscores the need for continued research to unravel the complexities surrounding EVs and their potential clinical implications. By identifying these challenges, this review contributes to ongoing efforts to optimize EV imaging techniques for clinical use. Ultimately, bridging the gap between research advancements and clinical applications will facilitate the integration of EV-based theranostics, marking a crucial step toward harnessing the full potential of EVs in medical practice.

mRNA-based therapeutics increasingly demonstrate significant potential in treating various diseases, including infectious diseases, cancers, and genetic disorders. Effective delivery systems are crucial for advancing mRNA therapeutics. Lipid nanoparticles (LNPs) serve as an excellent carrier, widely validated for their safety and tolerability in commercially available mRNA vaccines. Standard LNPs typically consist of four components: ionizable lipids (ILs), helper lipids, cholesterol, and polyethylene glycol-lipids (PEG-lipids), with the structural design of ILs gradually becoming a focal point of research interest. The chemical structures and formulations of the other components also significantly affect the delivery efficiency, targeting specificity, and stability of LNPs. The complex formulations of LNPs may hinder the clinical transformation of mRNA therapeutics and have raised widespread concerns about their safety. This review aims to summarize the progress of LNPs-based mRNA therapeutics in clinical trials, focusing on adverse effects that occurred during these trials. It also discusses representative innovations in LNP components, highlighting challenges and potential ways in this research field. We firmly believe this review will promote further improvements and designs of LNP compositions to optimize mRNA therapeutics. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Biology-Inspired Nanomaterials > Lipid-Based Structures.

Over the past two decades, ferritin has emerged as a promising nanoparticle for drug delivery, catalyzing the development of numerous prototypes capable of encapsulating a wide array of therapeutic agents. These ferritin-based nanoparticles exhibit selectivity for various molecular targets and are distinguished by their potential biocompatibility, unique symmetrical structure, and highly controlled size. The hollow interior of ferritin nanoparticles allows for efficient encapsulation of diverse therapeutic agents, enhancing their delivery and effectiveness. Despite these promising features, the anticipated clinical advancements have yet to be fully realized. As a physiological protein with a central role in both health and disease, ferritin can exert unexpected effects on physiology when employed as a drug delivery system. Many studies have not thoroughly evaluated the pharmacokinetic properties of the ferritin protein shell when administered in vivo, overlooking crucial aspects such as biodistribution, clearance, cellular trafficking, and immune response. Addressing these challenges is crucial for achieving the desired transition from bench to bedside. Biodistribution studies need to account for ferritin's natural accumulation in specific organs (liver, spleen, and kidneys), which may lead to off-target effects. Moreover, the mechanisms of clearance and cellular trafficking must be elucidated to optimize the delivery and reduce potential toxicity of ferritin nanoparticles. Additionally, understanding the immune response elicited by exogenous ferritin is essential to mitigate adverse reactions and enhance therapeutic efficacy. A comprehensive understanding of these physiological constraints, along with innovative solutions, is essential to fully realize the therapeutic potential of ferritin nanoparticles paving the way for their successful clinical translation.

Breast cancer is a highly widespread form of malignant tumor characterized by a high rate of recurrence and mortality; it primarily occurs when tumor cells spread to peripheral regions of the body. Macrophages have a significant impact on the proliferation and metastasis of breast cancer. The exosomes generated by these cells exhibit an extensive spectrum of capabilities in suppressing the spread of cancer cells. These feature very specific targeting properties for breast cancer cells and inhibit the proliferation of cancer cells by altering the immune milieu within the tumor. This study investigates methods for developing macrophage-derived exosomes, such as using protein-coupled exosome membranes to protect delivery contents, creating multifunctional biomimetic particles, and utilizing ultrasonic fusion to protect delivery contents. Furthermore, this paper addresses recent advances in producing macrophage exosomes from organic and inorganic materials. In general, targeted treatment for breast cancer could benefit greatly from creating drug delivery systems mediated by macrophage exosomes.

Cancer is considered a formidable global health threat, despite substantial strides in diagnosis, detection, and therapeutic strategies. Remarkable progress has been achieved in these realms, yet the survival rates for cancer patients have persisted at suboptimal levels over decades. Acknowledging the need to address the ongoing challenges in cancer survival rates, research efforts are being made to push the boundaries of innovation in diagnostic techniques, bioimaging, and drug delivery technologies. Over the past few years, nano(bio)technology-based approaches have been applied for biosensing and imaging applications to detect biochemical substances in various matrices. Among various nanoengineered particulates, quantum dots (QDs) have been recognized as versatile agents for these applications. QDs, often called artificial atoms, are characterized by the remarkable optical and electrical features which are essential for cytosensing, localized bioimaging and therapeutics. Here in this review, we have discussed various QDs as sensitive and selective agents for precise sensing and imaging of cancer cells. Both electrochemical and optical approaches have been used to describe the cytosensing detection methods. Furthermore, the bioimaging of malignant tumor cells and the drug delivery with therapeutic responses of QDs have also been highlighted. This review also lists the several kinds of QDs that are frequently used for such kinds of applications, such as carbon, graphene, zinc, and other types of hybrid-based QDs. Finally, to shed insight on prospective research, the advantages and potential of QDs are also highlighted. In this article, we also emphasize the limitations and address the difficulties associated with QDs in clinical applications in order to provide insights for potential solutions.

Contrast-enhanced ultrasound is currently used worldwide with clinical indications in cardiology and radiology, and it continues to evolve and develop through innovative technological advancements. Clinically utilized contrast agents for ultrasound consist of hydrophobic gas microbubbles stabilized with a biocompatible shell. These agents are used commonly in echocardiography, with emerging applications in cancer diagnosis and therapy. Microbubbles are a blood pool agent with diameters between 1 and 10 μm, which precludes their use in other extravascular applications. To expand the potential use of contrast-enhanced ultrasound beyond intravascular applications, sub-micron agents, often called nanobubbles or ultra-fine bubbles, have recently emerged as a promising tool. Combining the principles of ultrasound imaging with the unique properties of nanobubbles (high concentration and small size), recent work has established their imaging potential. Contrast-enhanced ultrasound imaging using these agents continues to gain traction, with new studies establishing novel imaging applications. We highlight the recent achievements in nonlinear nanobubble contrast imaging, including a discussion on nanobubble formulations and their acoustic characteristics. Ultrasound imaging with nanobubbles is still in its early stages, but it has shown great potential in preclinical research and animal studies. We highlight unexplored areas of research where the capabilities of nanobubbles may offer new advantages. As technology advances, this technique may find applications in various areas of medicine, including cancer detection and treatment, cardiovascular imaging, and drug delivery.

Pancreatic cancer is one of the tumors with poor prognosis and low survival due to late diagnosis, high resistance, and very limited effective therapeutic options. Thus, new pharmacological treatments are necessary to improve the prognosis of patients. In this context, nanoparticles represent an efficient system for transporting and administering therapeutic molecules. Furthermore, siRNA can be used in cancer treatment to selectively inhibit the expression of any target gene. Therefore, nanoparticles associated with siRNA have been tested as a new therapeutic strategy to solve the pancreatic cancer treatment failure in the clinical setting. The current article presents a systematic revision of the literature of the last 10 years in which nanoparticles loading siRNA are used in pancreatic cancer. This research was carried out in three databases (PubMed, Scopus, and Web of Science) obtaining 164 articles from which 37 were selected. Our results show an overall view of the high effectiveness of this new therapy that combines nanoparticles with genetic therapy in pancreatic cancer suggesting that siRNA-based medicines will likely open up a new therapeutic era in the treatment of this type of tumors.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that often causes joint pain, swelling, and functional impairments. Drug therapy is the main strategy used to alleviate the symptoms of RA; however, drug therapy may have several adverse effects, such as nausea, vomiting, abdominal pain, diarrhea, gastric ulcers, intestinal bleeding, hypertension, hyperglycemia, infection, fatigue, and indigestion. Moreover, long-term excessive use of drugs may cause liver and kidney dysfunction, as well as thrombocytopenia. Nanodrug delivery systems (NDDSs) can deliver therapeutics to diseased sites with the controlled release of the payload in an abnormal microenvironment, which helps to reduce the side effects of the therapeutics. Abnormalities in the microenvironment, such as a decreased pH, increased expression of matrix metalloproteinases (MMPs), and increased concentrations of reactive oxygen species (ROS), are associated with the progression of RA but also provide an opportunity to achieve microenvironment-responsive therapeutic release at the RA site. Microenvironment-responsive NDDSs may overcome the abovementioned disadvantages of RA therapy. Herein, we comprehensively review recent progress in the development of microenvironment-responsive NDDSs for RA treatment, including pH-, ROS-, MMP-, and multiresponsive NDDSs. Furthermore, the pathological microenvironment is highlighted in detail.

Messenger ribonucleic acid (mRNA) therapeutics are attracting attention as promising tools in cancer immunotherapy due to their ability to leverage the in vivo expression of all known protein sequences. Even small amounts of mRNA can have a powerful effect on cancer vaccines by promoting the synthesis of tumor-specific antigens (TSA) or tumor-associated antigens (TAA) by antigen-presenting cells (APC). These antigens are then presented to T cells, eliciting strong antitumor immune stimulation. The potential of mRNA can be further enhanced by expressing immunomodulatory agents, such as cytokines, antibodies, and chimeric antigen receptors (CAR), enhancing tumor immunity. Recent research also explores mRNA-encoded tumor death inducers or tumor microenvironment (TME) modulators. Despite its promise, the clinical translation of mRNA-based anticancer strategies faces challenges, including inefficient targeted delivery in vivo, failure of endosomal escape, and inadequate intracellular mRNA release, resulting in poor transfection efficiencies. Inspired by the approval of lipid nanoparticle-loaded mRNA vaccines against coronavirus disease 2019 (COVID-19) and the encouraging outcomes of mRNA-based cancer therapies in trials, innovative nonviral nanotechnology delivery systems have been engineered. These aim to advance mRNA-based cancer immunotherapies from research to clinical application. This review summarizes recent preclinical and clinical progress in lipid and polymeric nanomedicines for delivering mRNA-encoded antitumor therapeutics, including cytokines and antibody-based immunotherapies, cancer vaccines, and CAR therapies. It also addresses advanced delivery systems for direct oncolysis or TME reprogramming and highlights key challenges in translating these therapies to clinical use, exploring future perspectives, including the role of artificial intelligence and machine learning in their development.

Early detection of disease remains a crucial challenge in medicine. Delayed diagnosis often leads to limited treatment options, increased disease progression, and unfortunately, even death in some cases. To address this, the need for rapid, cost-effective, and noninvasive diagnostic tools is paramount. In recent years, electrochemical nanosensor-based point-of-care diagnostic tools have emerged as promising tools for various fields, with significant interest in their biological and chemical applications. These tiny sensors, utilizing nanoparticles and chemical agents, can detect and monitor physical components like disease biomarkers at the nanoscale, offering a unique advantage rarely found in other diagnostic methods. This unprecedented sensitivity has made them highly sought-after tools for biological applications, particularly in disease diagnosis. This review focuses specifically on electrochemical nanosensors and their potential as diagnostic tools in medicine. We will delve into their properties, applications, current advancements, and existing limitations.

In 2020, the top 10 causes of death among children and adolescents between the ages of 1 and 19 years old included cancer, congenital anomalies, heart disease, and chronic respiratory disease; all these conditions are potentially treatable with medical intervention. However, children exhibit specific physiological and developmental characteristics that can significantly impact drug pharmacokinetics, pharmacodynamics, and safety profile. These factors illustrate the importance of a heightened focus on pediatric drug development. Traditional drugs lack proper circulation, permeability, targeting, accumulation, and release, and they often require dose adjustments or modifications, which can result in suboptimal therapeutic outcomes and increased risks of adverse effects in pediatric patients. Nanomedicines have emerged as efficient drug delivery systems because of their unique properties, which can improve the solubility and stability of drugs by encapsulating them in different forms of nanoparticles. This review discusses the challenges of pediatric therapy, and the current state of nanomedicines for pediatric diseases in terms of Food and Drug Administration-approved nanomedicines, the types of diseases treated or diagnosed, and preclinical studies that have the potential to be translated to the clinic. In summary, nanomedicine holds significant potential for addressing the unique and pressing challenges associated with diagnosing and treating pediatric diseases.

Adjuvants augment the immunogenicity of vaccines when co-administered with messenger RNA (mRNA) antigens. In recent years, nanotechnology and nanoscience have seen significant growth, resulting in the discovery of synthetic small molecule compounds, natural extracts, and nanomaterials with self-adjuvant properties for nano delivery. The materials exhibit robust immune activity and efficiently activate various innate immune signaling pathways. Moreover, they possess a comparatively simple chemical composition in contrast to conventional adjuvants. This significantly streamlines the manufacturing process of vaccine formulations. Therefore, these self-adjuvant materials theoretically improve the reproducibility of adjuvant production and quality control. Herein, this review summarizes the current research and development progress of mRNA adjuvants, with a specific focus on various types of mRNA adjuvants, notably self-adjuvant nanomaterials. It discusses the current research status on a range of diseases and investigates the potential development of mRNA vaccine adjuvants.

In recent years, the application of radionuclides-containing nanomaterials in cancer treatment has garnered widespread attention. The diversity of nanomaterials allows researchers to selectively combine them with appropriate radionuclides for biomedical purposes, addressing challenges faced by peptides, small molecules, or antibodies used for radionuclide labeling. However, with advantages come challenges, and nanoradionuclides still encounter significant issues during clinical translation. This review summarized the recent progress of nanosized radionuclides for cancer treatment or diagnosis. The discussion began with representative radionuclides and the methods of incorporating them into nanomaterial structures. Subsequently, new combinations of nanomaterials and radionuclides, along with their applications, were introduced to demonstrate their future trends. The benefits of nanoradionuclides included optimized pharmacokinetic properties, enhanced disease-targeting efficacy, and synergistic application with other treatment techniques. Besides, the basic rule of this section was to summarize how these nanoradionuclides can truly impact the diagnosis and therapy of various cancer types. In the last part, the focus was devoted to the nanoradionuclides currently applicable in clinics and how to address the existing issues and problems based on our knowledge.

Ferroptosis is a lipid peroxidation-driven cell death route and has attracted enormous interest for cancer therapy. Distinct from other forms of regulated cell death, its process is involved with multiple metabolic pathways including lipids, bioenergetics, iron, and so on, which influence cancer cell ferroptosis sensitivity and communication with the immune cells in the tumor microenvironment. Development of novel technologies for harnessing the ferroptosis-associated metabolic regulatory network would profoundly improve our understanding of the immune responses and enhance the efficacy of ferroptosis-dependent immunotherapy. Interestingly, the recent advances in bio-derived material-based therapeutic platforms offer novel opportunities to therapeutically modulate tumor metabolism through the in situ delivery of molecular or material cues, which not only allows the tumor-specific elicitation of ferroptosis but also holds promise to maximize their immunostimulatory impact. In this review, we will first dissect the crosstalk between tumor metabolism and ferroptosis and its impact on the immune regulation in the tumor microenvironment, followed by the comprehensive analysis on the recent progress in biomaterial-based metabolic regulatory strategies for evoking ferroptosis-mediated antitumor immunity. A perspective section is also provided to discuss the challenges in metabolism-regulating biomaterials for ferroptosis-immunotherapy. We envision that this review may provide new insights for improving tumor immunotherapeutic efficacy in the clinic.

Messenger RNA (mRNA) technology has rapidly evolved, significantly impacting various therapeutic applications, including vaccines, protein replacement, and gene editing. Lipid nanoparticles (LNPs) have emerged as a pivotal nonviral vector for mRNA delivery, crucial for organ-targeted therapies. Despite their success, most LNP formulations predominantly target the liver, limiting their use in nonliver diseases. This review explores strategies to achieve organ-specific mRNA delivery using LNPs, including the discovery of new lipid structures, modification of targeting ligands, incorporation of additional components, and optimization of LNP formulations. These advancements aim to enhance the precision and efficacy of mRNA therapeutics across a broader range of diseases.

Cyclodextrins (CDs) belong to a class of cyclic oligosaccharides characterized by their toroidal shape consisting of glucose units linked via α-1,4-glycosidic bonds. This distinctive toroidal shape exhibits a dual nature, comprising a hydrophobic interior and a hydrophilic exterior, making CDs highly versatile in various pharmaceutical products. They serve multiple roles: they act as solubilizers, stabilizers, controlled release promoters, enhancers of drug bioavailability, and effective means of masking undesirable tastes and odors. Taking advantage of these inherent benefits, CDs have been integrated into numerous nanoscale drug delivery systems. The resulting nanomaterials exploit the exceptional properties of CDs, including their ability to solubilize hydrophobic drugs for substantial drug loading, engage in supramolecular complexation for engineered nanomaterials, increase bioavailability for improved therapeutic efficacy, stabilize labile drugs, and exhibit biocompatibility and versatility. This paper compiles recent studies on CD functional nanoscale drug delivery platforms. First, we described the physicochemical and toxicological aspects of CDs, CD/drug inclusion complexation, and their impact on improving drug bioavailability. We then summarized applications for CD-functional nano delivery systems based on polymeric, hybrid, lipid-based nanoparticles, and CD-based nanofibers. Particular interest was in the targeted applications and the function of the CD molecules used. In most applications, CD molecules were used for drug solubilization and loading, while in some studies, CD molecules were employed for supramolecular complexation to construct nanoscale drug delivery systems. Finally, the review concludes with a thoughtful consideration of the current challenges and outlook.

With the accelerated aging of the global population, the incidence of neurodegenerative diseases (NDDs) is increasing year by year. Because of the presence of the blood-brain barrier (BBB), the low concentration of the biomarkers in peripheral blood and the low penetration rate of the drugs through BBB into brain hinders the development of diagnosis and treatment of NDDs. As an effective mediator to penetrate through BBB in both directions, extracellular vesicles (EVs) have attracted much attention in the early diagnosis and treatment of NDDs because of their superior performance as drug carriers and detection biomarkers. Brain-derived EVs in body fluids contain disease-related biomolecules can be used as early diagnostic biomarkers for NDDs. In addition, as one of the subpopulations of EVs, exosomes, especially stem cell-derived exosomes, have great potential in the treatment of NDDs. The ability to cross the BBB, together with the feasibility of versatile functionalization of EV for NDDs pathogen targeting facilitate EVs a potential tool for targeted drug delivery systems for NDDs. In this review, the important role of EVs in the diagnosis and treatment of NDDs and the current research progress will be discussed. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease.

Nano-formulation has generated attention in the battle against cancer, because of its great flexibility, reduced adverse side effects, and accuracy in delivering drugs to target tissues dependent on the size and surface characteristics of the disease. The field of photodynamic treatment has advanced significantly in the past years. Photodynamic techniques that use nano-formulations have surfaced to further the field of nanotechnology in medicine, especially in cancer treatment. The pharmaceutical industry is seeing a growing trend toward enhanced drug formulation using nano-formulations such as liposomes, polymeric nanoparticles, dendrimers, nano-emulsions, and micelles. Natural extracts have also shown adverse effects when employed as photosensitizers in cancer therapy because they are cytotoxic when activated by light. Still, natural photosensitizers are a big part of cancer treatment. However, some shortcomings can be minimized by combining nano-formulations with these natural photosensitizers. The synergistic improvement in medication delivery that maintains or increases the mechanism of cell death in malignant cells has also been demonstrated by the combination of photodynamic therapy with nano-formulations and natural photosensitizers. Lastly, this review assesses the feasibility and potential of a photodynamic therapy system based on nano-formulations and natural photosensitizers in clinical treatment applications and briefly discusses the removal of toxic compounds associated with nano-formulations within cells.