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Tumor vaccines, a crucial immunotherapy, have gained growing interest because of their unique capability to initiate precise anti-tumor immune responses and establish enduring immune memory. Injected tumor vaccines passively diffuse to the adjacent draining lymph nodes, where the residing antigen-presenting cells capture and present tumor antigens to T cells. This process represents the initial phase of the immune response to the tumor vaccines and constitutes a pivotal determinant of their effectiveness. Nevertheless, the granularity paradox, arising from the different requirements between the passive targeting delivery of tumor vaccines to lymph nodes and the uptake by antigen-presenting cells, diminishes the efficacy of lymph node-targeting tumor vaccines. This study addressed this challenge by employing a vaccine formulation with a tunable, controlled particle size. Manganese dioxide (MnO 2 ) nanoparticles were synthesized, loaded with ovalbumin (OVA), and modified with A 50 or T 20 DNA single strands to obtain MnO 2 /OVA/A 50 and MnO 2 /OVA/T 20 , respectively. Administering the vaccines sequentially, upon reaching the lymph nodes, the two vaccines converge and simultaneously aggregate into MnO 2 /OVA/A 50 -T 20 particles through base pairing. This process enhances both vaccine uptake and antigen delivery. In vitro and in vivo studies demonstrated that, the combined vaccine, comprising MnO 2 /OVA/A 50 and MnO 2 /OVA/T 20 , exhibited robust immunization effects and remarkable anti-tumor efficacy in the melanoma animal models. The strategy of controlling tumor vaccine size and consequently improving tumor antigen presentation efficiency and vaccine efficacy via the DNA base-pairing principle, provides novel concepts for the development of efficient tumor vaccines., (© 2024. The Author(s).)

In recent years, manganese dioxide (MnO 2 ) nanoparticles with unique physicochemical properties have been widely used in many biomedical fields, such as biosensors, contrast agents, tumor therapy, and drug delivery. From these applications, MnO 2 nanoparticles have great clinical translation potential. However, by contrast, the in vitro and in vivo biosafety of MnO 2 nanoparticles have been deeply and thoroughly clarified for the clinical translation, which hinders their clinical applications. In this work, we deeply investigated the blood safety of MnO 2 nanoparticles by conducting a series of in vitro and in vivo experiments. These included the effects of MnO 2 nanoparticles on morphology of red blood cells, activation of platelets, coagulation functions, and toxicity of key organs. The obtained results show that these effects displayed a concentration-dependent manner of MnO 2 nanoparticles. Different safe concentration ranges could be found in the different experimental index. This study provides important guidance for the specific biomedical applications of MnO 2 nanoparticles, greatly accelerating their laboratory development and clinical translation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In the field of tumor immunotherapy, tumor vaccines have unique advantages including fewer side effects, tumor-specificity and immune memory, and hence attract more and more attention. In the development of tumor vaccines, a critical challenge lies in the exploitation of appropriate vaccine adjuvants/delivery systems that need to meet multiple requirements to achieve potent cellular immunity while simultaneously requiring single composition to simplify the clinical translation process. Among numerous materials, only manganese dioxide (MnO 2 ) nanoparticles with rare physicochemical properties seem to meet the demanding criteria of simplicity and multifunctionality. However, the potential of MnO 2 nanoparticles as vaccine adjuvants/delivery systems has not been well exploited, despite their widespread applications in the biomedical field. In this study, the mechanism and efficacy of single MnO 2 nanoparticles as a minimalist multi-mode tumor vaccine adjuvant/delivery system were fully investigated by using a model antigen ovalbumin (OVA) to construct tumor vaccines OVA/MnO 2 . The obtained results show that MnO 2 nanoparticles act as an ideal delivery system by multiple modes to deliver the antigen to the cytoplasm of dendritic cells to induce cellular immune response. Moreover, MnO 2 nanoparticles also act as a superior adjuvant depot to sustainably release Mn 2+ to enhance the immune response through a STING pathway in dendritic cells. Both the delivery function and the adjuvant effect of MnO 2 nanoparticles contribute to improved cellular immunity and anti-tumor efficacy of tumor vaccines OVA/MnO 2 . From the results, MnO 2 nanoparticles are found to be a promising minimalist multi-mode vaccine adjuvant/delivery system for the development of practical tumor vaccines.

CaCO 3 particles, due to their unique properties such as biodegradation, pH-sensitivity, and porous surface, have been widely used as carrier materials for delivering drugs, genes, vaccines, and other bioactive molecules. In these applications, CaCO 3 particles are often administered intravenously. In this sense, the interaction between CaCO 3 particles and blood components plays a key role in their delivery efficacy and biosafety, though the hemocompatibility of CaCO 3 particles has not been evaluated until now. Deficiency in the biosafety information has delayed the clinical use of CaCO 3 particles in delivery systems. In this work, we investigated the biosafety of CaCO 3 particles, focusing on their in vitro and in vivo effects on key blood components (red blood cells, platelets, etc) and coagulation functions. We found in vitro that high concentrations of CaCO 3 particles can cause the aggregation and hemolysis of red blood cells, with platelet activation and coagulation prolongation. In vivo , we found that intravenously injected CaCO 3 particles at 50 mg kg -1 significantly disturbed the red blood cells, and platelet-related blood routine indexes, but did not induce visible abnormalities in the tissue structures of the key organs. Overall, these effects may be due to the enormous adsorption capability of the porous surface of CaCO 3 particles. 0.1 mg ml -1 of the CaCO 3 particles exhibit excellent compatibility for their practical applications. These results would be expected to greatly promote the in vivo applications and clinical use of CaCO 3 particles in biomedicine., (© 2021 IOP Publishing Ltd.)

Natural polysaccharides, due to their outstanding merits, have received more and more attention in the field of drug delivery systems. In particular, polysaccharides seem to be the most promising materials in the preparation of nanometeric carriers. This review relates to the newest developments in the preparation of polysaccharides-based nanoparticles. In this review, four mechanisms are introduced to prepare polysaccharides-based nanoparticles, that is, covalent crosslinking, ionic crosslinking, polyelectrolyte complex, and the self-assembly of hydrophobically modified polysaccharides.

In this study, novel nanoparticles were prepared by polyelectrolyte complexation between heparin and chitosan on simple and mild conditions. The size, polydispersity, zeta potential, and morphology of the nanoparticles were characterized. Entrapment studies of the nanoparticles were conducted using bovine serum albumin (BSA) as a model protein. Specifically, the effects of the pH value of chitosan solution, chitosan molecular weight (MW), chitosan concentration, heparin concentration, and BSA concentration on the nanoparticle size, the nanoparticle yield, and BSA entrapment were studied in detail. We found that, the size and the yield of the nanoparticles were affected by the above factors. The nanoparticle yield played a crucial role in BSA entrapment, namely, more nanoparticles could encapsulate more BSA. At length, suitably high pH value of chitosan solution, moderate chitosan MW, increasing both heparin concentration and chitosan concentration at an optimal concentration ratio favored more nanoparticles formed and consequently a higher BSA entrapment efficiency., (Copyright 2007 Wiley Periodicals, Inc.)

Background: Immunochromatographic strips (ICSs) are a practical tool commonly used in point-of-care testing (POCT) applications. However, ICSs that are currently available have low sensitivity and require expensive equipment for quantitative analysis. These limitations prohibit their extensive use in areas where medical resources are scarce. Methods: We developed a novel POCT platform by integrating a gas generation biosensor with Au@Pt Core/Shell nanoparticle (Au@PtNPs)-based ICSs (G-ICSs). The resulting G-ICSs enabled the convenient and quantitative assessment of a target protein using the naked eye, without the need for auxiliary equipment or complicated computation. To assess this platform, C-reactive protein (CRP), a biomarker commonly used for the diagnosis of acute, infectious diseases was chosen as a proof-of-concept test. Results: The linear detection range (LDR) of the G-ICSs for CRP was 0.05–6.25 μg/L with a limit of detection (LOD) of 0.041 μg/L. The G-ICSs had higher sensitivity and wider LDR when compared with commonly used AuNPs and fluorescent-based ICSs. When compared with results from a chemiluminescent immunoassay, G-ICS concordance rates for CRP detection in serum samples ranged from 93.72 to 110.99%. Conclusions: These results demonstrated that G-ICSs have wide applicability in family diagnosis and community medical institutions, especially in areas with poor medical resources. [ABSTRACT FROM AUTHOR]

Polysaccharides based polyelectrolyte complex nanoparticles (PCNs) intended for use in the delivery of macromolecules were prepared by the self-assembly of deoxycholic acid hydrophobically modified chitosan (CS-DCA) core and then coated with sodium alginate (ALG) shell. The CS-DCA capable of forming nano-sized self-aggregates in medium was prepared by the grafting of DCA to CS. In order to increase the stability of nanoparticles and prevent burst release of drug in bloodstream, polyanionic ALG was coated on the surface of positively charged CS-DCA nanoparticles to form PCNs. Dynamic light scattering results revealed that the mean diameter of the PCNs was about 330 nm, larger than that of uncoated nanoparticles (~150 nm). The zeta potential was big enough to keep the stability of PCNs (−28 mV); no size change was found even upon 1 month storage. Bovine serum albumin could be easily incorporated into the PCNs with encapsulation efficiency (>44 %) and keep a sustained manner without burst release when exposed to PBS (pH 7.4) at 37 °C. These results suggested that PCNs may be a promising drug carrier for a prolonged and sustained delivery in the bloodstream. [ABSTRACT FROM AUTHOR]

Abstract The aim of this work was to examine the formation and properties of a novel polyelectrolyte complex of drug carrier system for the delivery of doxorubicin (DOX), which consists of hyaluronic acid (HA) coated hydrophobically modified chitosan (CS). Various batches of polyelectrolyte complexes with the molar ratio of deoxycholic acid (DCA) and chitosan (CS) of 0.1, 0.2, 0.3 were prepared, and were termed as CS-DCA 10 , CS-DCA 20 , and CS-DCA 30 respectively. The samples were characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), Transmission electron microscopy (TEM), nuclear magnetic resonance hydrogen spectrum (1H NMR) and dynamic light scattering (DLS). Particle sizes of synthesized polyelectrolyte complex nanoparticles (PCNs) were found to be in the range of 280–310 nm, larger than those of uncoated nanoparticles (~150 nm). The PCNs have large zeta potentials (about 26 mV) which make them stable and no sizes' change was determined. DOX could be easily incorporated into the PCNs with encapsulation efficiency (56%) and kept a sustained release manner without burst effect when exposed to PBS (pH 7.4) at 37 °C. Overall, these findings confirmed the potential of these PCNs for drug carrier and prolonged and sustained delivery in the bloodstream. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]