Query: nanoparticles as immunostimulants

title: AIEgen coupled upconversion nanoparticles eradicate solid tumors through dual mode ROS activation
abstract: Integration of AIEgens with upconversion nanoparticles inhibits tumor recurrence and metastasis. Reactive oxygen species (ROS) are essential for the regulation of antitumor immune responses, where they could induce immunogenic cell death, promote antigen presentation, and activate immune cells. Here, we report the development of near infrared (NIR) driven immunostimulants, based on coupling upconversion nanoparticles with aggregation induced emission luminogens (AIEgens) to integrate the immunological effects of ROS for enhanced adaptive antitumor immune responses. Intratumorally injected AIEgen upconversion nanoparticles produce high dose ROS under high power NIR irradiation, which induces immunogenic cell death and antigen release. These nanoparticles can also capture the released antigens and deliver them to lymph nodes. Upon subsequent low power NIR treatment of lymph nodes, low dose ROS are generated to further trigger efficient T cell immune responses through activation of dendritic cells, preventing both local tumor recurrence and distant tumor growth. The utility of dual mode pumping power on AIEgen coupled upconversion nanoparticles offers a powerful and controllable platform to activate adaptive immune systems for tumor immunotherapy.

title: Immunostimulatory effects of cell wall based nanoparticles in boiled Glycyrrhizae radix water extracts involves TLR4
abstract: A number of immunostimulant effects of herbal medicines have been reported; however, the underlying mechanisms of their immunostimulatory effects have not been elucidated in detail. Our previous study showed that sugar based nanoparticles derived from cell walls acted as the immunostimulatory component of boiled Glycyrrhizae radix water extracts. Therefore, the aim of the present study was to clarify the molecular mechanisms by which these cell wall based nanoparticles functioned as immunostimulants. Mouse macrophage RAW blue cells were stimulated by these nanoparticles and several immunological effects were investigated. When phosphorylation of nuclear factor kB (NF) kB p65 subunit was increased, the expression of the inflammatory cytokines interleukin 6 and tumor necrosis factor a were induced via NF kB. On the other hand, Toll like receptor 4 recognizes cell wall components of bacteria and fungi. In the present study, it was also shown that these cell wall based nanoparticles serve an immunostimulatory role as ligands of Toll like receptor 4 by RNA interference experiments. The results of the present study suggested that the signaling pathway of nanoparticles obtained from boiled Glycyrrhizae radix water extracts, at least partially involved TLR4 and downstream signaling from this receptor, resulting in the immunostimulatory effects of these nanoparticles in RAW blue cells.

title: Optimization Characterization of Silver Nanoparticles fromRhizophora mucronata Mangrove bark extract
abstract: The major goal of nanotechnology is to produce nano materials with controlled properties like, size and shape which can serve the human being, marine species and ecosystem through diverse applications. Rhizophora mucronata Mangrove bark extract supported the synthesis of highly effective andsubstantial AgNPs. The synthesis of AgNPs from 1.0 mL of Rhizophora mucronata extract was optimized at different Physiological and biological condition at a concentration of pH 7.0 and 1.0 mM ofAgNO3at 37*C.The synthesized AgNPs were characterized by ZETA potential and Atomic force Microscopy (AFM) The Zeta potential value was 20.3 mV wherein the AFMenvisage the 3D structure of the nanoparticles ranging from~78 to~99 nm. The results confirm,consistent and high degree of stable nanoparticles of Rhizophora mucronata Mangrove bark extract could be used as immunostimulants, which will expand the possibilities of further research on disease controlling trialson marine animals.

title: Intranasal Delivery of Immunotherapeutic Nanoformulations for Treatment of Glioma Through in situ Activation of Immune Response
abstract: Some chemotherapeutics have been shown to induce both the release of damage associated molecular patterns (DAMPs) and the production of type I interferon (IFN I) leading to immunogenic cell death (ICD) However, the standard chemotherapy drug for glioma, temozolomide (TMZ) cannot induce ICD as it cannot activate IFN I signaling. Moreover, inefficient delivery of immunostimulants across the blood brain barrier (BBB) is the main obstacle to overcome in order to induce local immune responses in the brain.  A new oligonucleotide nanoformulation (Au@PP)/poly(I:C) was constructed by coating gold nanoparticles (AuNPs) with methoxypolyethylene glycol (mPEG) detachable (d) polyethyleneimine (PEI) (Au@PP) followed by inducing the formation of electrostatic interactions with polyinosinic polycytidylic acid (poly(I:C) Intracranial GL261 tumor bearing C57BL/6 mice were used to explore the therapeutic outcomes of Au@PP/poly(I:C) plus TMZ in vivo. The anti tumor immune response in the brain induced by this treatment was analyzed by RNA sequencing and immunohistochemical analyses.  Au@PP/poly(I:C) induced IFN I production after endocytosis into glioma cells in vitro. Additionally, Au@PP/poly(I:C) was efficiently accumulated in the glioma tissue after intranasal administration, which allowed the nanoformulation to enter the brain while bypassing the BBB. Furthermore, Au@PP/poly(I:C) plus TMZ significantly improved the overall survival of the tumor bearing mice compared with group TMZ only. RNA sequencing and immunohistochemical analyses revealed efficient immune response activation and T lymphocyte infiltration in the Au@PP/poly(I:C) plus TMZ group.  This study demonstrates that intranasal administration of Au@PP/poly(I:C) combined with TMZ induces ICD, thereby stimulating an in situ immune response to inhibit glioma growth.

title: Emerging nanomedicines for effective breast cancer immunotherapy
abstract: Breast cancer continues to be the most frequently diagnosed malignancy among women, putting their life in jeopardy. Cancer immunotherapy is a novel approach with the ability to boost the host immune system to recognize and eradicate cancer cells with high selectivity. As a promising treatment, immunotherapy can not only eliminate the primary tumors, but also be proven to be effective in impeding metastasis and recurrence. However, the clinical application of cancer immunotherapy has faced some limitations including generating weak immune responses due to inadequate delivery of immunostimulants to the immune cells as well as uncontrolled modulation of immune system, which can give rise to autoimmunity and nonspecific inflammation. Growing evidence has suggested that nanotechnology may meet the needs of current cancer immunotherapy. Advanced biomaterials such as nanoparticles afford a unique opportunity to maximize the efficiency of immunotherapy and significantly diminish their toxic side effects. Here we discuss recent advancements that have been made in nanoparticle involving breast cancer immunotherapy, varying from direct activation of immune systems through the delivery of tumor antigens and adjuvants to immune cells to altering immunosuppression of tumor environment and combination with other conventional therapies.

title: Toll like receptors agonists based nanomedicines as veterinary immunotherapies
abstract: Many infections affecting animals enter across mucosa, needing of secretory immunity to reject the disease; protection against some pathogens must be early, fast, and specifically elicited, while from others must be wide enough to fight against variable serotypes. Today, however, most veterinary vaccines are injectable (not recommended for chicken and small fishes) aimed to control clinical signs instead of eradicating the disease and poor inducers of secretory immunity. These drawbacks are compensated by vaccination with live attenuated agents, by using potentially toxic oily adjuvants and with indiscriminate use of antibiotics. In this review, the benefits of commercial and experimental nanomedicines acting as immunostimulants and vaccine adjuvants made of toll like receptor (TLR) agonists loaded in nanoparticles (NP TLR agonists) are presented. NP TLR agonists induce a magnified, site limited triggering of innate immunity; also allow modifying the administration route from injectable to mucosal or nebulized, provide structural protection to TLR agonists and avoid their diffusion far from the administration site. Future implementation of immunotherapies based on NP TLR agonists will be discussed as a function of scale production feasibility.

title: Macrophage like THP 1 cells show effective uptake of silica nanoparticles carrying inactivated diphtheria toxoid for vaccination
abstract: Nanoparticles may be used in vaccinology as an antigen delivery and/or an immunostimulant to enhance immunity. Porous silica has been identified as an effective adjuvant for more than a decade, and we have therefore investigated the take up rate by an immortalized macrophage like cell line of a number of mesoporous silica nanoparticles (MSNPs) with differing diameter and pore size. The MSNPs were synthesized using a sol gel reaction and post synthesis removal of the template. The MSNPs showed a clear distribution in take up rate peaking at 217 nm, whereas a comparison with solid spherical nanoparticles showed a similar distribution peaking at 377 nm. The MSNPs were investigated before and after loading with antigen. Diphtheria toxoid was used as a proof of concept antigen and showed a peak macrophage internalization of 53.42% for loaded LP3 particles which had a diameter of 217.75 5.44 nm and large 16.5 nm pores. Optimal MSNP sizes appeared to be in the 200 400 nm range, and larger pores showed better antigen loading. The mesoporous silica particles were shown to be generally biocompatible, and cell viability was not altered by the loading of particles with or without antigen.

title: Immunostimulatory effect of chitosan conjugated green copper oxide nanoparticles in tumor immunotherapy.
abstract: Current study demonstrates the immunogenic role of biopolymer coated green synthesized copper oxide nanoparticles by the induction of cellular immunity through the activation immune cells. Alongside humoral immunity response was triggered by the surface coated NPs through IgG response which indicate the adjuvanic role of the nano conjugate. Th1 (Type 1 and Type 2 helper T cells) and Th2 cells were activated after the treatment with nano conjugate and act as an immunostimulant which would inhibit the proliferation of breast cancer (MCF 7) and cervical cancer (HeLa) cells in in vitro. Solid tumor induced by 4 T1 cells were also inhibited in in vivo Balb/C mice model. Secretion of pro inflammatory cytokines and the increase in CD 4 populations indicate the activation of immune cells in the current study. Immunotherapy by the help of metal nano conjugate can be an effective tool to eradicate the cancer cells from the system.

title: Polyethylenimine coated PLGA nanoparticles encapsulated Angelica sinensis polysaccharide as an adjuvant for H9N2 vaccine to improve immune responses in chickens compared to Alum and oil based adjuvants.
abstract: Inactivated H9N2 influenza vaccines required adjuvants to induce strong immune responses to protect poultry from the infections of H9N2 influenza viruses. Recently, positively charged nanoparticles based adjuvant delivery systems have been extensively investigated as the novel vaccine adjuvant due to the protection antigens and drugs from degradation, promoting antigens and drugs uptake by antigen presenting cells (APCs) and inducing strong humoral and cellular immune responses. In this study, the immunostimulant Angelica sinensis polysaccharide (ASP) was encapsulated into Poly (lactic co glycolic acid) PLGA nanoparticles, and the Polyethylenimine (PEI) was coated on the nanoparticles to develop a novel adjuvant (ASP PLGA PEI) To further investigate the adjuvant activities of ASP PLGA PEI nanoparticles for H9N2 vaccines in chickens and compare the adjuvant activities of nanoparticles adjuvant and conventional adjuvants (Alum and oil based adjuvant) the H9N2 antigen was incubated with three different adjuvants and then immunized with chickens to evaluate the ability of inducing humoral and cellular immune responses. The results revealed that compared to Alum adjuvant, ASP PLGA PEI nanoparticles adjuvant stimulated higher antibody responses, promoted the activation of CD4+ T cells and CD8+ T cells, increased the expression of Th1 cytokines IFN g. Compared to oil based adjuvant (ISA 206) ASP PLGA PEI nanoparticles adjuvant induced comparable antibody immune responses at later period after immunization, improved the activation of CD4+ T cells and CD8+ T cells. Therefore, compared to Alum and oil based adjuvant, the ASP PLGA PEI nanoparticles serve as an efficient adjuvant for H9N2 vaccine and have the potential to induce vigorous humoral and cellular immune responses in chickens.

title: Tri modal imaging of gold dotted magnetic nanoparticles for magnetic resonance imaging, computed tomography and intravascular ultrasound: an in vitro study.
abstract: To examine the multimodal contrasting ability of gold dotted magnetic nanoparticles (Au*MNPs) for magnetic resonance (MR) computed tomography (CT) and intravascular ultrasound (IVUS) imaging.  Au*MNPs were prepared by adapting an impregnation method, without using surface capping reagents and characterized (transmission electron microscopy, x ray diffraction and Fourier transform infrared spectroscopy) with their in vitro cytotoxicity assessed, followed by imaging assessments.  The contrast enhancing ability of Au*MNPs was shown to be concentration dependent across MR, CT and IVUS imaging. The Au content of the Au*MNP led to evident increases of the IVUS signal.  We demonstrated that Au*MNPs showed concentration dependent contrast enhancing ability in MRI and CT imaging, and for the first time in IVUS imaging due to the Au content. These Au*MNPs are promising toward solidifying tri modal imaging based theragnostics.