Respiratory diseases remain challenging to treat, with current efforts primarily focused on managing symptoms rather than maintaining overall lung health. Traditional treatment methods, such as oral or parenteral administration of antiviral, antibacterial, and anti-inflammatory drugs, face limitations. These include difficulty in delivering therapeutic agents to pathogens residing deep in the airways and the risk of severe side effects due to high systemic drug concentrations. The growing threat of drug-resistant pathogens further complicates infection management.

The lung's large surface area offers an attractive target for inhalation-based drug delivery. Nanoparticles (NP) enable uniform and sustained drug distribution across the alveolar network, overcoming challenges posed by complex lung anatomy. Recent breakthroughs in nanorobots (NR) have demonstrated precise navigation through biological environments, delivering therapies directly to affected lung areas with enhanced accuracy. Nanotechnology has also shown promise in treating lung cancer, with nanoparticles engineered to overcome biological barriers, improve drug solubility, and enable controlled drug release.

This review explores the progress of NP and NR in addressing challenges in pulmonary drug delivery. These innovations allow targeted delivery of nucleic acids, drugs, or peptides to the pulmonary epithelium with unprecedented accuracy, offering significant potential for improving therapeutic effectiveness in respiratory disorders.

Cancer has become a highly prevalent disease and poses serious threats to human health. Conventional cancer treatments still face high risks of recurrence. Training the immune system to recognize and eliminate tumors via external stimulation, such as vaccines, emerges as a promising approach for cancer prevention and treatment. However, injectable vaccines may have limited immune activation, causing difficulties in maintaining long-term immune surveillance of tumorigenesis by tumor-specific cytotoxic T cells. Here, degradable zwitterionic cryogels were prepared using the cryogelation technique. The cryogenic preparation maintained the biological activities of tumor antigens and immune adjuvants loaded in the cryogels. The macroporous structure endowed the injectability of cryogels into the body via conventional syringes. In the presence of proteases, the cryogels degraded, allowing sustained release of antigens and adjuvants, ensuring continued dendritic cell (DC) recruitment and antigen presentation to maturing tumor-specific cytotoxic T cells. In vivo experiments demonstrated that the cryogel cancer vaccines elicited robust immune activation and effectively modulated tumor microenvironments. The combination with photothermal therapy significantly inhibited tumor growth, showing great potential for preventing postoperative recurrence. Additionally, the zwitterionic cryogels were biocompatible without obvious toxicities during degradation. The cryogels could serve as effective vaccine platforms to prevent cancer recurrence after surgery.

Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis, treated primarily through surgery and chemotherapy. Other treatments like radiation or thermal ablation for metastases have limited success, and recurrence is common. More effective management options are needed. Magnetic iron oxide nanoparticles (IONP) show promise in cancer treatment due to their ability to be modified for selective uptake by cancer cells. This study investigated IONP uptake in ACC cell lines (H295R, HAC-15, MUC-1) using a multicellular model with endothelial cells (HUVEC) and monocytes. IONP uptake was concentration- and time-dependent, with optimal uptake at 10 μg/mL. IONP were found in the cytoplasm and intracellular vesicles of ACC cells. However, endothelial cells and monocytes also absorbed IONP, reducing uptake by ACC cells. These findings suggest ACC cells actively take up IONP, but better targeting is needed to enhance uptake specificity and efficiency.

Despite significant therapeutic advances, multiple myeloma (MM) remains a challenging, incurable, hematological malignancy. The efficacy of traditional chemotherapy and currently available anti-MM agents is in part limited by their adverse effects, which restrict their therapeutic potential. Nanotherapeutics is an emerging field of cancer therapy that can overcome the biological and chemical barriers of existing anticancer drugs. This review presents an overview of recent advancements in nanoparticle- and immunotherapy-based drug delivery systems for MM treatment. It further delves into the targeting strategies, mechanism of controlled drug release, and challenges associated with the development of drug delivery systems for the treatment of MM.

Cancer is becoming the main public health problem globally. Conventional chemotherapy approaches are slowly being replaced or complemented by new therapies that avoid the loss of healthy tissue, limit off-targets, and eradicate cancer cells. Immunotherapy is nowadays an important strategy for cancer treatment, that uses the host's anti-tumor response by activating the immune system and increasing the effector cell number, while, minimizing cancer's immune-suppressor mechanisms. Its efficacy is still limited by poor therapeutic targeting, low immunogenicity, antigen presentation deficiency, impaired T-cell trafficking and infiltration, heterogeneous microenvironment, multiple immune checkpoints and unwanted side effects, which could benefit from improved delivery systems, able to release immunotherapeutic agents to tumor microenvironment and immune cells. Nanoparticles (NPs) for immunotherapy (Nano-IT), have a huge potential to solve these limitations. Natural and/or synthetic, targeted and/or stimuli-responsive nanoparticles can be used to deliver immunotherapeutic agents in their native conformations to the site of interest to enhance their antitumor activity. They can also be used as co-adjuvants that enhance the activity of IT effector cells. These nanoparticles can be engineered in the natural context of cell-derived extracellular vesicles (EVs) or exosomes or can be fully synthetic. In this review, a detailed SWOT analysis is done through the comparison of engineered-synthetic and naturaly-derived nanoparticles in terms of their current and future use in cancer immunotherapy.

Cancer immunotherapy represents a promising targeted treatment by leveraging the patient's immune system or adoptive transfer of active immune cells to selectively eliminate cancer cells. Despite notable clinical successes, conventional immunotherapies face significant challenges stemming from the poor infiltration of endogenous or adoptively transferred cytotoxic T cells in tumors, immunosuppressive tumor microenvironment and the immune evasion capability of cancer cells, leading to limited efficacy in many types of solid tumors. Overcoming these hurdles is essential to broaden the applicability of immunotherapies. Recent advances in nanotherapeutics have emerged as an innovative tool to overcome these challenges and enhance the therapeutic potential of tumor immunotherapy. The unique biochemical and biophysical properties of nanomaterials offer advantages in activation of immune cells in vitro for cell therapy, targeted delivery, and controlled release of immunomodulatory agents in vivo. Nanoparticles are excellent carriers for tumor associated antigens or neoantigen peptides for tumor vaccine, empowering activation of tumor specific T cell responses. By precisely delivering immunomodulatory agents to the tumor site, immunoactivating nanoparticles can promote tumor infiltration of endogenous T cells or adoptively transferred T cells into tumors, to overcoming delivery and biological barriers in the tumor microenvironment, augmenting the immune system's ability to recognize and eliminate cancer cells. This review provides an overview of the current advances in immunotherapeutic approaches utilizing nanotechnology. With a focus on discussions concerning strategies to enhance activity and efficacy of cytotoxic T cells and explore the intersection of engineering nanoparticles and immunomodulation aimed at bolstering T cell-mediated immune responses, we introduce various nanoparticle formulations designed to deliver therapeutic payloads, tumor antigens and immunomodulatory agents for T cell activation. Diverse mechanisms through which nanoparticle-based approaches influence T cell responses by improving antigen presentation, promoting immune cell trafficking, and reprogramming immunosuppressive tumor microenvironments to potentiate anti-tumor immunity are examined. Additionally, the synergistic potential of combining nanotherapeutics with existing immunotherapies, such as immune checkpoint inhibitors and adoptive T cell therapies is explored. In conclusion, this review highlights emerging research advances on activation of cytotoxic T cells using nanoparticle agents to support the promises and potential applications of nanoparticle-based immunomodulatory agents for cancer immunotherapy.

Breast cancer appears as the major cause of cancer-related deaths in women, with more than 2 260 000 cases reported worldwide in 2020, resulting in 684 996 deaths. Triple-negative breast cancer (TNBC), characterized by the absence of estrogen, progesterone, and human epidermal growth factor type 2 receptors, represents ≈20% of all breast cancers. TNBC has a highly aggressive clinical course and is more prevalent in younger women. The standard therapy for advanced TNBC is chemotherapy, but responses are often short-lived, with high rate of relapse. The lack of therapeutic targets and the limited therapeutic options confer to individuals suffering from TNBC the poorest prognosis among breast cancer patients, remaining a major clinical challenge. In recent years, advances in cancer nanomedicine provided innovative therapeutic options, as nanoformulations play an important role in overcoming the shortcomings left by conventional therapies: payload degradation and its low solubility, stability, and circulating half-life, and difficulties regarding biodistribution due to physiological and biological barriers. In this integrative review, the recent advances in the nanomedicine field for TNBC treatment, including the novel nanoparticle-, exosome-, and hybrid-based therapeutic formulations are summarized and their drawbacks and challenges are discussed for future clinical applications.

The use of biological agents for the management of chronic dermatological pathologies such as psoriasis is becoming more common every day. Until now, antibodies against tumor necrosis factors (TNF-α) inhibitors, interleukin IL-17 inhibitors, IL-12/23 inhibitors, and IL-23 inhibitors have been marketed as biological therapies for psoriasis, showing excellent results with a minimal number of adverse events. Initially, the first biological treatments were associated primarily with opportunistic infections. Later, specific adverse events were described depending on the biological agent used: TNF-α inhibitors were linked to tuberculosis, while anti-IL-17 agents were associated with candidiasis and worsening of inflammatory bowel disease (IBD). However, such therapies warrant a cautious screening protocol to detect pre-existing infections, mainly tuberculosis and chronic viral infections such as hepatitis. Human immunodeficiency virus (HIV) is only screened in case of suspicion and in some institutional protocols. We present the clinical case of a person living with HIV under optimal virological control, in which the use of biological therapy was imperative to control psoriasis and he also presented with great severity. Until now there is no official statement on the use or not of biologicals in this particular population.

The programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint constitutes an inhibitory pathway best known for its regulation of cluster of differentiation 8 (CD8)+ T cell-mediated immune responses. Engagement of PD-L1 with PD-1 expressed on CD8+ T cells activates downstream signaling pathways that culminate in T cell exhaustion and/or apoptosis. Physiologically, these immunosuppressive effects exist to prevent autoimmunity, but cancer cells exploit this pathway by overexpressing PD-L1 to facilitate immune escape. Intravenously (IV) administered immune checkpoint inhibitors (ICIs) that block the interaction between PD-1/PD-L1 have achieved great success in reversing T cell exhaustion and promoting tumor regression in various malignancies. However, these ICIs can cause immune-related adverse events (irAEs) due to off-tumor toxicities which limits their therapeutic potential. Therefore, considerable effort has been channeled into exploring alternative delivery strategies that enhance tumor-directed delivery of PD-1/PD-L1 ICIs and reduce irAEs. Here, we briefly describe PD-1/PD-L1-targeted cancer immunotherapy and associated irAEs. We then provide a detailed review of alternative delivery approaches, including locoregional (LDD)-, oncolytic virus (OV)-, nanoparticle (NP)-, and ultrasound and microbubble (USMB)-mediated delivery that are currently under investigation for enhancing tumor-specific delivery to minimize toxic off-tumor effects. We conclude with a commentary on key challenges associated with these delivery methods and potential strategies to mitigate them.

Anticancer therapy urgently needs the development of novel strategies. An innovative molecular target is represented by circular RNAs (circRNAs), single-strand RNA molecules with the 5' and 3' ends joined, characterized by a high stability. Although circRNA properties and biological functions have only been partially elucidated, their relationship and involvement in the onset and progression of cancer have emerged. Specific targeting of circRNAs may be obtained with antisense oligonucleotides and silencing RNAs. Nanotechnology is at the forefront of research for perfecting their delivery. Continuous efforts have been made to develop novel nanoparticles (NPs) and improve their performance, materials, and properties regarding biocompatibility and targeting capabilities. Applications in various fields, from imaging to gene therapy, have been explored. This review sums up the smart strategies developed to directly target circRNAs with the fruitful application of NPs in this context.

There is a myriad of diseases that plague the world ranging from infectious, cancer and other chronic diseases with varying interventions. However, the dynamism of causative agents of infectious diseases and incessant mutations accompanying other forms of chronic diseases like cancer, have worsened the treatment outcomes. These factors often lead to treatment failure via different drug resistance mechanisms. More so, the cost of developing newer drugs is huge. This underscores the need for a paradigm shift in the drug delivery approach in order to achieve desired treatment outcomes. There is intensified research in nanomedicine, which has shown promises in improving the therapeutic outcome of drugs at preclinical stages with increased efficacy and reduced toxicity. Regardless of the huge benefits of nanotechnology in drug delivery, challenges such as regulatory approval, scalability, cost implication and potential toxicity must be addressed via streamlining of regulatory hurdles and increased research funding. In conclusion, the idea of nanotechnology in drug delivery holds immense promise for optimizing therapeutic outcomes. This work presents opportunities to revolutionize treatment strategies, providing expert opinions on translating the huge amount of research in nanomedicine into clinical benefits for patients with resistant infections and cancer.

Peptides have become an indispensable tool in engineering of multifunctional nanostructure platforms for biomedical applications such as targeted drug and gene delivery, imaging and biosensing. They can be covalently incorporated into a variety of nanoparticles (NPs) including polymers, metallic nanoparticles, and others. Using different bioconjugation techniques, multifunctional peptide-modified NPs can be formulated to produce therapeutical and diagnostic platforms offering high specificity, lower toxicity, biocompatibility, and stimuli responsive behavior. Targeting peptides can direct the nanoparticles into specific tissues for targeted drug and gene delivery and imaging applications due to their specificity towards certain receptors. Furthermore, due to their stimuli-responsive features, they can offer controlled release of therapeutics into desired sites of disease. In addition, peptide-based biosensors and imaging agents can provide non-invasive detection and monitoring of diseases including cancer, infectious diseases, and neurological disorders. In this review, we covered the design and formulation of recent peptide-based NP platforms, as well as their utilization in in vitro and in vivo applications such as targeted drug and gene delivery, targeting, sensing, and imaging applications. In the end, we provided the future outlook to design new peptide conjugated nanomaterials for biomedical applications.

The concept of nanomedicine has evolved significantly in recent decades, leveraging the unique phenomenon known as the enhanced permeability and retention (EPR) effect. This has facilitated major advancements in targeted drug delivery, imaging, and individualized therapy through the integration of nanotechnology principles into medicine. Numerous nanomedicines have been developed and applied for disease treatment, with a particular focus on cancer therapy. Recently, nanomedicine has been utilized in various advanced fields, including diagnosis, vaccines, immunotherapy, gene delivery, and tissue engineering. Multifunctional nanomedicines facilitate concurrent medication delivery, therapeutic monitoring, and imaging, allowing for immediate responses and personalized treatment plans. This review concerns the major advancement of nanomaterials and their potential applications in the biological and medical fields. Along with this, we also mention the various clinical translations of nanomedicine and the major challenges that nanomedicine is currently facing to overcome the clinical translation barrier.

Cancer immunotherapy and vaccine development have significantly improved the fight against cancers. Despite these advancements, challenges remain, particularly in the clinical delivery of immunomodulatory compounds. The tumor microenvironment (TME), comprising macrophages, fibroblasts, and immune cells, plays a crucial role in immune response modulation. Nanoparticles, engineered to reshape the TME, have shown promising results in enhancing immunotherapy by facilitating targeted delivery and immune modulation. These nanoparticles can suppress fibroblast activation, promote M1 macrophage polarization, aid dendritic cell maturation, and encourage T cell infiltration. Biomimetic nanoparticles further enhance immunotherapy by increasing the internalization of immunomodulatory agents in immune cells such as dendritic cells. Moreover, exosomes, whether naturally secreted by cells in the body or bioengineered, have been explored to regulate the TME and immune-related cells to affect cancer immunotherapy. Stimuli-responsive nanocarriers, activated by pH, redox, and light conditions, exhibit the potential to accelerate immunotherapy. The co-application of nanoparticles with immune checkpoint inhibitors is an emerging strategy to boost anti-tumor immunity. With their ability to induce long-term immunity, nanoarchitectures are promising structures in vaccine development. This review underscores the critical role of nanoparticles in overcoming current challenges and driving the advancement of cancer immunotherapy and TME modification.

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

Glioblastoma is an aggressive primary brain tumor that poses many therapeutic difficulties because of the high rate of proliferation, genetic variability, and its immunosuppressive microenvironment. The theory of cancer immunoediting, which includes the phases of elimination, equilibrium, and escape, offers a paradigm for comprehending interactions between the immune system and glioblastoma. Immunoediting indicates the process by which immune cells initially suppress tumor development, but thereafter select for immune-resistant versions leading to tumor escape and progression. The tumor microenvironment (TME) in glioblastoma is particularly immunosuppressive, with regulatory T cells and myeloid-derived suppressor cells being involved in immune escape. To achieve an efficient immunotherapy for glioblastoma, it is crucial to understand these mechanisms within the TME. Existing immunotherapeutic modalities such as chimeric antigen receptor T cells and immune checkpoint inhibitors have been met with some level of resistance because of the heterogeneous nature of the immune response to glioblastoma. Solving these issues is critical to develop novel strategies capable of modulating the TME and re-establishing normal immune monitoring. Further studies should be conducted to identify the molecular and cellular events that underlie the immunosuppressive tumor microenvironment in glioblastoma. Comprehending and modifying the stages of immunoediting in glioblastoma could facilitate the development of more potent and long-lasting therapies.

Nanotechnology has expanded what can be achieved in our approach to cancer treatment. The ability to produce and engineer functional nanoparticle formulations to elicit higher incidences of tumor cell radiolysis has resulted in substantial improvements in cancer cell eradication while also permitting multi-modal biomedical functionalities. These radiosensitive nanomaterials utilize material characteristics, such as radio-blocking/absorbing high-Z atomic number elements, to mediate localized effects from therapeutic irradiation. These materials thereby allow subsequent scattered or emitted radiation to produce direct (e.g., damage to genetic materials) or indirect (e.g., protein oxidation, reactive oxygen species formation) damage to tumor cells. Using nanomaterials that activate under certain physiologic conditions, such as the tumor microenvironment, can selectively target tumor cells. These characteristics, combined with biological interactions that can target the tumor environment, allow for localized radio-sensitization while mitigating damage to healthy cells. This review explores the various nanomaterial formulations utilized in cancer radiosensitivity research. Emphasis on inorganic nanomaterials showcases the specific material characteristics that enable higher incidences of radiation while ensuring localized cancer targeting based on tumor microenvironment activation. The aim of this review is to guide future research in cancer radiosensitization using nanomaterial formulations and to detail common approaches to its treatment, as well as their relations to commonly implemented radiotherapy techniques.

Cancer is one of the most well-studied diseases and there have been significant advancements over the last few decades in understanding its molecular and cellular mechanisms. Although the current treatments (e.g., chemotherapy, radiotherapy, gene therapy and immunotherapy) have provided complete cancer remission for many patients, cancer still remains one of the most common causes of death in the world. The main reasons for the poor response rates for different cancers include the lack of drug specificity, drug resistance and toxic side effects (i.e., in healthy tissues). For addressing the limitations of conventional cancer treatments, nanotechnology has shown to be an important field for constructing different nanoparticles for destroying cancer cells. Due to their size (i.e., less than 1 μm), nanoparticles can deliver significant amounts of cancer drugs to tumors and are able to carry moieties (e.g., folate, peptides) for targeting specific types of cancer cells (i.e., through receptor-mediated endocytosis). Liposomes, composed of phospholipids and an interior aqueous core, can be used as specialized delivery vehicles as they can load different types of cancer therapy agents (e.g., drugs, photosensitizers, genetic material). In addition, the ability to load imaging agents (e.g., fluorophores, radioisotopes, MRI contrast media) enable these nanoparticles to be used for monitoring the progress of treatment. This review examines a wide variety of different liposomes for cancer theranostics, with the different available treatments (e.g., photothermal, photodynamic) and imaging modalities discussed for different cancers.

Cancer immunotherapy employing checkpoint inhibitors holds great promise across diverse cancers; nonetheless, a substantial proportion of patients (ranging from 55 to 87%) remain unresponsive to this treatment. To amplify therapeutic efficiency, we propose a synergistic therapeutic strategy that entails the deployment of targeted nano-sized particles carrying Toll-like receptor (TLR) agonists to the tumor site. This innovative approach seeks to activate intratumoral antigen-presenting cells using bioengineered outer membrane vesicles (OMVs) derived from gram-negative bacteria. These OMVs possess inherent attributes of surface-exposed immune stimulators and TLR-activating components, rendering them intriguing candidates for investigation. These OMVs were meticulously designed to selectively target cancer cells exhibiting an overexpression of epidermal growth factor receptor (EGFR). To gauge the precision of this targeting, the conducted affinity-based assays aimed at determining the equilibrium dissociation constant of the single-chain variable fragment employed for this purpose. In vitro experiments confirmed the OMVs' proficiency in adhering to EGFR-overexpressed cancer cells. Moreover, the evaluation extended to an in vivo context, where the therapeutic effect of nanovesicles was appraised within the tumor microenvironment of the triple-negative breast cancer mouse model. Notably, both intraperitoneal and intratumoral administrations of nanovesicles exhibited the ability to activate natural killer cells and skew M2 macrophage towards an M1 phenotype. The combined scrutiny of in vitro and in vivo findings underscores the potential efficiency of OMVs as a promising strategy for future anti-tumor endeavors.

Gold nanoparticles (AuNPs) have received great attention for various medical applications due to their unique physicochemical properties. AuNPs with tunable optical properties in the visible and near-infrared regions have been utilized in a variety of applications such as in vitro diagnostics, in vivo imaging, and therapeutics. Among the applications, this review will pay more attention to recent developments in diagnostic and therapeutic applications based on the photothermal (PT) effect of AuNPs. In particular, the PT effect of AuNPs has played an important role in medical applications utilizing light, such as photoacoustic imaging, photon polymerase chain reaction (PCR), and hyperthermia therapy. First, we discuss the fundamentals of the optical properties in detail to understand the background of the PT effect of AuNPs. For diagnostic applications, the ability of AuNPs to efficiently convert absorbed light energy into heat to generate enhanced acoustic waves can lead to significant enhancements in photoacoustic signal intensity. Integration of the PT effect of AuNPs with PCR may open new opportunities for technological innovation called photonic PCR, where light is used to enable fast and accurate temperature cycling for DNA amplification. Additionally, beyond the existing thermotherapy of AuNPs, the PT effect of AuNPs can be further applied to cancer immunotherapy. Controlled PT damage to cancer cells triggers an immune response, which is useful for obtaining better outcomes in combination with immune checkpoint inhibitors or vaccines. Therefore, this review examines applications to nanomedicine based on the PT effect among the unique optical properties of AuNPs, understands the basic principles, the advantages and disadvantages of each technology, and understands the importance of a multidisciplinary approach. Based on this, it is expected that it will help understand the current status and development direction of new nanoparticle-based disease diagnosis methods and treatment methods, and we hope that it will inspire the development of new innovative technologies.

Immunophenotyping, which is the identification of immune cell subsets based on antigen expression, is an integral technique used to determine changes of cell composition and activation in various disease states or as a response to different stimuli. As nanoparticles are increasingly utilized for diagnostic and therapeutic applications, it is important to develop methodology that allows for the evaluation of their immunological impact. Therefore, the development of techniques such as immunophenotyping are desirable. Currently, the most common technique used to perform immunophenotyping is multicolor flow cytometry.

We developed two distinct multicolor flow cytometry immunophenotyping panels which allow for the evaluation of the effects of nanoparticles on the composition and activation status of treated human peripheral blood mononuclear cells. These two panels assess the presence of various lymphoid and myeloid-derived cell populations as well as aspects of their activation statuses-including proliferation, adhesion, co-stimulation/presentation, and early activation-after treatment with controls or nanoparticles. To conduct assay performance qualification and determine the applicability of this method to preclinical characterization of nanoparticles, we used clinical-grade nanoformulations (AmBisome, Doxil and Feraheme) and research-grade PAMAM dendrimers of different sizes (G3, G4 and G5) and surface functionalities (amine-, carboxy- and hydroxy-).

We found that formulations possessing intrinsic fluorescent properties (e.g., Doxil and AmBisome) interfere with accurate immunophenotyping; such interference may be partially overcome by dilution. In the absence of interference (e.g., in the case of dendrimers), nanoparticle size and surface functionalities determine their effects on the cells with large amine-terminated dendrimers being the most reactive.

The core devotion of this study is to develop a generalized model by means of a recently proposed fractional technique in order to anticipate the enhancement in the thermal efficiency of engine oil because of the dispersion of graphene and magnesia nanoparticles. In addition to investigating the synergistic attributes of the foregoing particles, this work evaluates shape impacts for column, brick, tetrahedron, blade, and lamina-like shapes. In the primary model, the flow equation is coupled with concentration and energy functions. This classical system is transmuted into a fractional environment by generalizing mathematical expressions of thermal and diffusion fluxes by virtue of the Prabhakar fractional operator. In this study, ramped flow and temperature slip conditions are simultaneously applied for the first time to examine the behavior of a hybrid nanofluid. The mathematical analysis of this problem involves the incorporation of dimension-independent parameters into the model and the execution of the Laplace transform for the consequent equations. By doing so, exact solutions are derived in the form of Mittag-Leffler functions. Multiple illustrations are developed by dint of exact solutions to chew over all aspects of temperature variations and flow dynamics. For the preparation of these illustrations, the details of parametric ranges are as follows: [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text]. The contribution of differently shaped nanoparticles, volume proportions, and fractional parameters in boosting the heat-transferring attributes of engine oil is also anticipated. In this regard, results for Nusselt number are provided in tabular form. Additionally, a brief analysis of shear stress is carried out for fractional parameters and various combinations of magnesia, graphene, and engine oil. This investigation anticipates that engine oil's hybridization with magnesia and graphene would result in a 33% increase in its thermal performance, which evidently improves its industrial significance. The enhancement in Schmidt number yields an improvement in the mass transfer rate. An increment in collective volume fraction leads to raising the profile of the thermal field. However, the velocity indicates a decreasing behavior. Nusselt number reaches its highest value ([Formula: see text]) for the lamina shape of considered particles. When the intensity of the buoyancy force augments, it causes the velocity to increase.

In recent years, nanoparticles derived from cellular membranes have been increasingly explored for the prevention and treatment of human disease. With their flexible design and ability to interface effectively with the surrounding environment, these biomimetic nanoparticles can outperform their traditional synthetic counterparts. As their popularity has increased, researchers have developed novel ways to modify the nanoparticle surface to introduce new or enhanced capabilities. Moving beyond naturally occurring materials derived from wild-type cells, genetic manipulation has proven to be a robust and flexible method by which nanoformulations with augmented functionalities can be generated. In this review, an overview of genetic engineering approaches to express novel surface proteins is provided, followed by a discussion on the various biomedical applications of genetically modified cellular nanoparticles.

Protein Corona (PC) of nanoparticles is a structure which composed of one or more layers of proteins adsorbed on the surface of nanomaterials, and the formation of PC is a universal process of spontaneous randomness. We take advantage of the formation principle of the PC, developed a simple and efficient method for label protein to nanoparticles.

The artificialed protein corona (APC) on the surface of nanoparticles was synthesized via the artificialed methods of desolvation aggregation and crosslinking with control.

The dosage of precipitator and the ratio of protein to magnetic nanoparticles (MNPs)(particle size: 3 nm) were optimized, and the core-shell nanoparticles with narrow particle size (particle size: 10 nm) distribution were obtained. The MNPs with APC were characterized by transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). Additionally, a hemolysis test on prepared MNPs was conducted with APC. The presence of APC coating on the surface of MNPs showed an improving effect to reduce the cytotoxicity. Cellular toxicity of MNPs with APC was also investigated on HFF1 cell lines. And the cells survival in the presence of APC coated MNPs and display neither reduced metabolism nor cytostatic effect. The functional test of the MNPs with APC showed that proteins can be modified and labeled onto magnetic nanoparticles and retain their original activity.

This marking method is gentle and effective. And the properties of the APC propose MNPs as a promising candidate for multifunctional biomedical applications.

The therapy of life-threatening fungal infections is limited and needs urgent improvement. This is in part due to toxic side effects of clinically used antifungal compounds or their limited delivery to fungal structures. Until today, it is a matter of debate how drugs or drug-delivery systems can efficiently reach the intracellular lumen of fungal cells and how this can be improved. Here, we addressed both questions by applying two different polymeric particles for delivery of compounds. Their formulation was based on two biocompatible polymers, i.e., poly(lactic-co-glycolic acid)_50:50 and poly(methyl methacrylate-stat-methacrylic acid)_90:10 yielding particles with hydrodynamic diameters ranging from 100 to 300 nm. The polymers were covalently labeled with the fluorescent dye DY-550 to monitor the interaction between particles and fungi by confocal laser scanning microscopy. Furthermore, the fluorescent dye coumarin-6 and the antifungal drug itraconazole were successfully encapsulated in particles to study the fate of both the cargo and the particle when interacting with the clinically most important human-pathogenic fungi Aspergillus fumigatus, A. terreus, Candida albicans, and Cryptococcus neoformans. While the polymers were exclusively located on the fungal surface, the encapsulated cargo was efficiently transported into fungal hyphae, indicated by increased intracellular fluorescence signals due to coumarin-6. In accordance with this finding, compared to the pristine drug a reduced minimal inhibitory concentration for itraconazole was determined, when it was encapsulated. Together, the herein used polymeric particles were not internalized by pathogenic fungi but were able to efficiently deliver hydrophobic cargos into fungal cells.

Skin cancers, especially melanomas, present a formidable diagnostic and therapeutic challenge to the scientific community. Currently, the incidence of melanomas shows a high increase worldwide. Traditional therapeutics are limited to stalling or reversing malignant proliferation, increased metastasis, or rapid recurrence. Nonetheless, the advent of immunotherapy has led to a paradigm shift in treating skin cancers. Many state-of-art immunotherapeutic techniques, namely, active vaccination, chimeric antigen receptors, adoptive T-cell transfer, and immune checkpoint blockers, have achieved a considerable increase in survival rates. Despite its promising outcomes, current immunotherapy is still limited in its efficacy. Newer modalities are now being explored, and significant progress is made by integrating cancer immunotherapy with modular nanotechnology platforms to enhance its therapeutic efficacy and diagnostics. Research on targeting skin cancers with nanomaterial-based techniques has been much more recent than other cancers. Current investigations using nanomaterial-mediated targeting of nonmelanoma and melanoma cancers are directed at augmenting drug delivery and immunomodulation of skin cancers to induce a robust anticancer response and minimize toxic effects. Many novel nanomaterial formulations are being discovered, and clinical trials are underway to explore their efficacy in targeting skin cancers through functionalization or drug encapsulation. The focus of this review rivets on theranostic nanomaterials that can modulate immune mechanisms toward protective, therapeutic, or diagnostic approaches for skin cancers. The recent breakthroughs in nanomaterial-based immunotherapeutic modulation of skin cancer types and diagnostic potentials in personalized immunotherapies are discussed.

Prostaglandin E2 (PGE2) is an important maturation mediator for dendritic cells (DCs). However, increased PGE2 levels in the tumor exert immunosuppressive effects on DCs by signaling through two E-Prostanoid (EP) receptors: EP2 and EP4. Blocking EP-receptor signaling of PGE2 with antagonists is currently being investigated for clinical applications to enhance anti-tumor immunity. In this study, we investigated a new delivery approach by encapsulating EP2/EP4 antagonists in polymeric nanoparticles. The nanoparticles were characterized for size, antagonist loading, and release. The efficacy of the encapsulated antagonists to block PGE2 signaling was analyzed using monocyte-derived DCs (moDCs). The obtained nanoparticles were sized between 210 and 260 nm. The encapsulation efficacy of the EP2/EP4 antagonists was 20% and 17%, respectively, and was further increased with the co-encapsulation of both antagonists. The treatment of moDCs with co-encapsulation EP2/EP4 antagonists prevented PGE2-induced co-stimulatory marker expression. Even though both antagonists showed a burst release within 15 min at 37 °C, the nanoparticles executed the immunomodulatory effects on moDCs. In summary, we demonstrate the functionality of EP2/EP4 antagonist-loaded nanoparticles to overcome PGE2 modulation of moDCs.

Breast cancer is now the most prevalent cancer in females, therefore, it is essential to identify factors affecting its initiation and progression. Mesenchymal stem cells (MSCs) have received considerable attention in stem cell-based therapies and drug delivery applications. Because the therapeutic potential of MSCs is primarily achieved by their paracrine effects, thus identifying and employing bioactive molecules that promote the paracrine activity of MSCs is crucial for their efficient use in cancer treatment. Thymoquinone (TQ) has many biomedical properties, including anti-inflammatory, anti-diabetic, anti-aging, anti-cancer, etc. In addition, it has been found that TQ affects the self-renewal and immunomodulatory properties of MSCs. The present study aimed to investigate the effect of TQ-treated mouse bone marrow-derived MSCs conditioned medium (TQ-MSC-CM) on the biological characteristics of breast cancer cell line MCF7. MSCs were cultured and treated with TQ for 24 h. The TQ-MSC-CM and MSC-CM were collected, and their effects were investigated on ROS production, mitochondrial membrane potential (MMP), cell death, cell cycle, and migration of MCF7 cells by DCFDA-cellular ROS assay, Rhodamine-123 MMP assay, Annexin-PI staining and Caspase-3/7 activity assays, PI-staining and flow-cytometry, and in vitro wound healing assay, respectively. Moreover, the effects of TQ-MSC-CM and MSC-CM were studied on Cdk4, Sox2, c-Met, and Bcl2 gene expression by real-time PCR. Results demonstrated that MSC-CM and TQ-MSC-CM did not have a significant effect on the apoptosis induction in MCF7 cells; however, they significantly stimulated necrosis in the cells. Although TQ-MSC-CM promoted ROS production in MCF7 cells, it decreased the MMP of the cells. TQ-MSC-CM also induced Bcl2 anti-apoptosis gene expression and Casp-3/7 activity in cells. In addition, although MSC-CM induced MCF7 cells to enter the cell cycle, TQ-MSC-CM inhibited its progression. TQ-MSC-CM also downregulated the Cdk4 and Sox2 gene expression. Furthermore, TQ-MSC-CM induced the migration potential of MCF7 in a c-Met-independent manner. Altogether, we conclude that TQ may induce programmed necrosis and inhibits the proliferation and migration of the breast cancer cells by affecting the paracrine activity of MSCs.

Cancer is still one of the leading causes of death worldwide. Nanotechnology, particularly nanoparticle-based platforms, is at the leading edge of current cancer management research. Polymer-based nanosystems have piqued the interest of researchers owing to their many benefits over other conventional drug delivery systems. Polymers derived from both natural and synthetic sources have various biomedical applications due to unique qualities like porosity, mechanical strength, biocompatibility, and biodegradability. Polymers such as poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), and polyethylene glycol (PEG) have been approved by the USFDA and are being researched for drug delivery applications. They have been reported to be potential carriers for drug loading and are used in theranostic applications. In this review, we have primarily focused on the aforementioned polymers and their conjugates. In addition, the therapeutic and diagnostic implications of polymer-based nanosystems have been briefly reviewed. Furthermore, the safety of the developed polymeric formulations is crucial, and we have discussed their biocompatibility in detail. This article also discusses recent developments in block co-polymer-based nanosystems for cancer treatment. The review ends with the challenges of clinical translation of polymer-based nanosystems in drug delivery for cancer therapy.

Anti-PD-(L)1 treatment is indicated for patients with mismatch repair-deficient (MMRD) tumors, regardless of tumor origin. However, the response rate is highly heterogeneous across MMRD tumors. The objective of the study is to find a score that predicts anti-PD-(L)1 response in patients with MMRD tumors.

Sixty-one patients with various origin of MMRD tumors and treated with anti-PD-(L)1 were retrospectively included in this study. An expert radiologist annotated all tumors present at the baseline and first evaluation CT-scans for all the patients by circumscribing them on their largest axial axis (single slice), allowing us to compute an approximation of their tumor volume. In total, 2120 lesions were annotated, which led to the computation of the total tumor volume for each patient. The RECIST sum of target lesions' diameters and neutrophile-to-lymphocyte (NLR) were also reported at both examinations. These parameters were determined at baseline and first evaluation and the variation between the first evaluation and baseline was calculated, to determine a comprehensive score for overall survival (OS) and progression-free survival (PFS).

Total tumor volume at baseline was found to be significantly correlated to the OS (p-value: 0.005) and to the PFS (p-value:<0.001). The variation of the RECIST sum of target lesions' diameters, total tumor volume and NLR were found to be significantly associated to the OS (p-values:<0.001, 0.006,<0.001 respectively) and to the PFS (<0.001,<0.001, 0.007 respectively). The concordance score combining total tumor volume and NLR variation was better at stratifying patients compared to the tumor volume or NLR taken individually according to the OS (pairwise log-rank test p-values: 0.033,<0.001, 0.002) and PFS (pairwise log-rank test p-values: 0.041,<0.001, 0.003).

Total tumor volume appears to be a prognostic biomarker of anti-PD-(L)1 response to immunotherapy in metastatic patients with MMRD tumors. Combining tumor volume and NLR with a simple concordance score stratifies patients well according to their survival and offers a good predictive measure of response to immunotherapy.

Colorectal cancer (CRC) is one of the most devastating diseases worldwide. Immunotherapeutic agents for CRC treatment have shown limited efficacy due to the immunosuppressive tumor microenvironment (TME). In this context, various types of nanoparticles (NPs) have been used to reverse the immunosuppressive TME, potentiate the effect of immunotherapeutic agents and reduce their systemic side effects. Many advantages could be offered by NPs, related to drug-loading efficiency, particle size and others that can potentially aid the delivery of immunotherapeutic agents. The recent research on how nano-based immunotherapy can remodel the immunosuppressive TME of CRC and hence boost the antitumor immune response, as well as the challenges that face clinical translation of NPs and future perspectives, are summarized in this review article.

Cancer is a leading cause of death worldwide. Nowadays, the therapies are inadequate and spur demand for improved technologies. Rapid growth in nanotechnology and novel nanomedicine products represents an opportunity to achieve sophisticated targeting strategies and multi-functionality. Nanomedicine is increasingly used to develop new cancer diagnosis and treatment methods since this technology can modulate the biodistribution and the target site accumulation of chemotherapeutic drugs, thereby reducing their toxicity. Cancer nanotechnology and cancer immunotherapy are two parallel themes that have emerged over the last few decades while searching for a cure for cancer. Immunotherapy is revolutionizing cancer treatment, as it can achieve unprecedented responses in advanced-stage patients, including complete cures and long-term survival. A deeper understanding of the human immune system allows the establishment of combination regimens in which immunotherapy is combined with other treatment modalities (as in the case of the nanodrug Ferumoxytol). Furthermore, the combination of gene therapy approaches with nanotechnology that aims to silence or express cancer-relevant genes via one-time treatment is gradually progressing from bench to bedside. The most common example includes lipid-based nanoparticles that target VEGF-Α and KRAS pathways. This review focuses on nanoparticle-based platforms utilized in recent advances aiming to increase the efficacy of currently available cancer therapies. The insights provided and the evidence obtained in this paper indicate a bright future ahead for immuno-oncology applications of engineering nanomedicines.

In contrast to conventional anti-tumor agents, nano-carriers allow co-delivery of distinct drugs in a cell type-specific manner. So far, many nanodrug-based immunotherapeutic approaches aim to target and kill tumor cells directly or to address antigen presenting cells (APC) like dendritic cells (DC) in order to elicit tumor antigen-specific T cell responses. Regulatory T cells (Treg) constitute a major obstacle in tumor therapy by inducing a pro-tolerogenic state in APC and inhibiting T cell activation and T effector cell activity. This review aims to summarize nanodrug-based strategies that aim to address and reprogram Treg to overcome their immunomodulatory activity and to revert the exhaustive state of T effector cells. Further, we will also discuss nano-carrier-based approaches to introduce tumor antigen-specific chimeric antigen receptors (CAR) into T cells for CAR-T cell therapy which constitutes a complementary approach to DC-focused vaccination.

Due to the complex physiological structure, microenvironment and multiple physiological barriers, traditional anti-cancer drugs are severely restricted from reaching the tumour site. Cell-penetrating peptides (CPPs) are typically made up of 5-30 amino acids, and can be utilised as molecular transporters to facilitate the passage of therapeutic drugs across physiological barriers. Up to now, CPPs have widely been used in many anti-cancer treatment strategies, serving as an excellent potential choice for oncology treatment. However, their drawbacks, such as the lack of cell specificity, short duration of action, poor stability in vivo, compatibility problems (i.e. immunogenicity), poor therapeutic efficacy and formation of unwanted metabolites, have limited their further application in cancer treatment. The cellular uptake mechanisms of CPPs involve mainly endocytosis and direct penetration, but still remain highly controversial in academia. The CPPs-based drug delivery strategy could be improved by clever design or chemical modifications to develop the next-generation CPPs with enhanced cell penetration capability, stability and selectivity. In addition, some recent advances in targeted cell penetration that involve CPPs provide some new ideas to optimise CPPs.

Our previous study demonstrates that a juxtamembrane 2 (JM2) mimic peptide can inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism remains unclear. In this study, JM2 is found to suppress the growth of 4T1 breast tumors by inducing apoptosis and inhibiting the proliferation of 4T1 tumor cells. Further study indicates that JM2 can stimulate the mitochondria to gather near the microtubule-organizing center of tumor cells and subsequently induce ROS-induced ROS release responses, which results in mitochondrial dysfunction and mitochondria-mediated apoptosis. In addition, JM2 can arrest cell cycle in S phase by regulating the expression of cell cycle-related proteins and consequently inhibit proliferation of tumor cells. Then, a previously designed JM2 grafted hyaluronic acid (HA) injectable hydrogel system (HA-JM2) is injected in a breast tumor-resected model and the HA-JM2 hydrogel can inhibit the malignant proliferation of residual tumor cells and suppress the breast tumor recurrence. These findings not only confirm the application potentials of JM2 in anti-tumor therapy and tumor post-surgery treatments but also provide greater understanding on the mechanisms by which JM2 inhibits tumor growth.

Cancer is the second leading cause of death worldwide. Traditional approaches, such as surgery, chemotherapy, and radiotherapy have been the main cancer therapeutic modalities in recent years. Cancer immunotherapy is a novel therapeutic modality that potentiates the immune responses of patients against malignancy. Immune checkpoint proteins expressed on T cells or tumor cells serve as a target for inhibiting T cell overactivation, maintaining the balance between self-reactivity and autoimmunity. Tumors essentially hijack the immune checkpoint pathway in order to survive and spread. Immune checkpoint inhibitors (ICIs) are being developed as a result to reactivate the anti-tumor immune response. Recent advances in nanotechnology have contributed to the development of successful, safe, and efficient anticancer drug systems based on nanoparticles. Nanoparticle-based cancer immunotherapy overcomes numerous challenges and offers novel strategies for improving conventional immunotherapies. The fundamental and physiochemical properties of nanoparticles depend on various cancer therapeutic strategies, such as chemotherapeutics, nucleic acid-based treatments, photothermal therapy, and photodynamic agents. The review discusses the use of nanoparticles as carriers for delivering immune checkpoint inhibitors and their efficacy in cancer combination therapy.