Regulation of Oxygen in the Tumor Microenvironment Synergizes with Immunotherapy to Suppress Tumor Progression.

Hypoxia represents a crucial characteristic of the tumor microenvironment, which is closely related to cell proliferation, angiogenesis, and metabolic responses. These factors will further promote tumor progression, increase tumor invasion, and enhance tumor metastasis potential. A hypoxic microenvironment will also inhibit the activity of infiltrated immune cells in the tumor microenvironment, leading to the failure of cancer immunotherapy.

In vitro and in vivo evaluation of immune response of poly(lactic acid) nanoparticles with different end groups.

Poly(lactic acid) (PLA) has excellent properties of biodegradability and biocompatibility, which is a US Food and Drug Administration (FDA) approved biopolymer for the preparation of safe and effective vaccines, drugs, and gene delivery systems. However, there still exists a great problem whether and how the end group affects the immune response of PLA vaccines. Therefore, the aim of this study was to evaluate the in vitro and in vivo of immune response of PLA nanoparticles (NPs) with carboxyl (COOH) and ester (COOR) end groups.

Tumor Microenvironment Regulation and Cancer Targeting Therapy Based on Nanoparticles.

Although we have made remarkable achievements in cancer awareness and medical technology, there are still tremendous increases in cancer incidence and mortality. However, most anti-tumor strategies, including immunotherapy, show low efficiency in clinical application. More and more evidence suggest that this low efficacy may be closely related to the immunosuppression of the tumor microenvironment (TME).

Virus-like Particles for TEM Regulation and Antitumor Therapy.

Tumor development and metastasis are intimately associated with the tumor microenvironment (TME), and it is difficult for vector-restricted drugs to act on the TME for long-term cancer immunotherapy. Virus-like particles (VLPs) are nanocage structures self-assembled from nucleic acid free viral proteins. Most VLPs range from 20-200 nm in diameter and can naturally drain into lymph nodes to induce robust humoral immunity.

Ion Interference Therapy of Tumors Based on Inorganic Nanoparticles.

As an essential substance for cell life activities, ions play an important role in controlling cell osmotic pressure balance, intracellular acid-base balance, signal transmission, biocatalysis and so on. The imbalance of ion homeostasis in cells will seriously affect the activities of cells, cause irreversible damage to cells or induce cell death. Therefore, artificially interfering with the ion homeostasis in tumor cells has become a new means to inhibit the proliferation of tumor cells.

Local Destruction of Tumors for Systemic Immunoresponse: Engineering Antigen-Capturing Nanoparticles as Stimulus-Responsive Immunoadjuvants.

Immunotherapy has established a new paradigm for cancer treatment and made many breakthroughs in clinical practice. However, the rarity of immune response suggests that additional intervention is necessary. In recent years, it has been reported that local tumor destruction (LTD) can cause cancer cell death and induce an immunologic response.

Intracellular signaling pathway in dendritic cells and antigen transport pathway in vivo mediated by an OVA@DDAB/PLGA nano-vaccine.

Background: Poly(D, L-lactic-co-glycolic acid) (PLGA) nanoparticles have potential applications as a vaccine adjuvant and delivery system due to its unique advantages as biodegradability and biocompatibility.

Experimental: We fabricated cationic solid lipid nanoparticles using PLGA and dimethyl-dioctadecyl-ammonium bromide (DDAB), followed by loading of model antigen OVA (antigen ovalbumin, OVA) to form an OVA@DDAB/PLGA nano-vaccine. And we investigated the intracellular signaling pathway in dendritic cells in vitro and antigen transport pathway and immune response in vivo mediated by an OVA@DDAB/PLGA nano-vaccine.

Micro- and Nanoencapsulated Hybrid Delivery System (MNEHDS): A Novel Approach for Colon-Targeted Oral Delivery of Berberine.

Berberine (BBR) is currently explored in the oral treatment of many disorders, especially in those involving inflammatory processes. Nanotechnology-based drug delivery systems are emerging as an effective approach for improving the poor oral absorption/bioavailability of BBR. To optimize the BBR immunoregulatory effects on a specific part of the gastrointestinal tract, here we describe a micro- and nanoencapsulated hybrid delivery system (MNEHDS) for colon-targeted oral delivery of BBR and test its therapeutic efficacy in a murine colitis model.

Tumor microenvironment remodeling and tumor therapy based on M2-like tumor associated macrophage-targeting nano-complexes.

Among the many immunosuppressive cells in the tumor microenvironment, tumor-associated-macrophages (TAMs) are well known to contribute to tumor development. TAMs can be conditioned (polarized) to transition between classical M1-like macrophages, or alternatively to M2-like macrophages. Both are regulated by signaling molecules in the microenvironment.

Multifunctional biomimetic nanoparticles loading baicalin for polarizing tumor-associated macrophages.

Immunosuppression and immune tolerance lead tumor cells to evade immune system surveillance and weaken drug efficacy. The presence of various immunosuppressive cells in the tumor microenvironment, especially tumor-associated macrophages (TAMs), has been shown to be a driving force in tumor initiation and development. Reversion of the TAM phenotype is an effective way to induce a subsequent antitumor immune response.

A Novel Human Papillomavirus 16 L1 Pentamer-Loaded Hybrid Particles Vaccine System: Influence of Size on Immune Responses.

Cervical cancer remains the second-most prevalent female malignancy around the world, leading to a great majority of cancer-related mortality that occurs mainly in developing countries. Developing an effective and low-cost vaccine against human papillomavirus (HPV) infection, especially in medically underfunded areas, is urgent. Compared with vaccines based on HPV L1 viruslike particles (VLPs) in the market, recombinant HPV L1 pentamer expressed in Escherichia coli represents a promising and potentially cost-effective vaccine for preventing HPV infection.

Potential Hepatitis B Vaccine Formulation Prepared by Uniform-Sized Lipid Hybrid PLA Microparticles with Adsorbed Hepatitis B Surface Antigen.

For the purpose of strengthening the immunogenicity of the hepatitis B vaccine, which contains hepatitis B surface antigen (HBsAg), the development of biodegradable poly(lactic acid) (PLA) microparticles (MPs) modified with the cationic surfactant didodecyldimethylammonium bromide (DDAB) was attempted. DDAB-PLA MPs with an uniform size of about 1 μm were prepared in a simple and mild way. DDAB-PLA MPs with increased surface charge enhanced antigen adsorption capacity compared to plain PLA MPs.

Fabrication and characterization of DDAB/PLA-alginate composite microcapsules as single-shot vaccine.

The most effective method to reduce chronic hepatitis B virus infection is the universal implementation of vaccination. The commercial aluminum-based vaccines need multiple-injection protocols for complete protection resulting in poor compliance in developing countries. It is necessary to develop single-shot vaccine formulations.

Prompt and Robust Humoral Immunity Elicited by a Conjugated Chimeric Malaria Antigen with a Truncated Flagellin.

As one of the pathogen-associated molecular patterns (PAMPs), flagellin is recently utilized as a potent adjuvant for many subunit vaccines. In this study, a truncated flagellin (tFL) with deletion of the hypervariable regions was adopted as a carrier-adjuvant by chemical conjugation with a chimeric malaria antigen M.RCAg-1 (M312) via a heterobifunctional polyethylene glycol (PEG) linker.

Porous Nanohydroxyapatite/Collagen Scaffolds Loading Insulin PLGA Particles for Restoration of Critical Size Bone Defect.

Insulin is considered to be a classical central regulator of energy homeostasis. Recently, the effect of insulin on bone has gained a lot of attention, but little attention has been paid to the application in bone tissue engineering. In this study, porous nanohydroxyapatite/collagen (nHAC) scaffolds incorporating poly lactic-co-glycolic acid (PLGA) particles were successfully developed as an insulin delivery platform for bone regeneration.

Facile fabrication of varisized calcium carbonate microspheres as vaccine adjuvants.

Functional calcium carbonate (CaCO) particles of micron and submicron sizes used in catalysis and biomedicine have attracted considerable attention for decades. In this paper, the process parameters for CaCO crystallization were systematically investigated. Our experimental results demonstrated the significance of temperature during fabrication.

Adjuvanticity Regulation by Biodegradable Polymeric Nano/microparticle Size.

Polymeric nano/microparticles as vaccine adjuvants have been researched in experimental and clinical studies. A more profound understanding of how the physicochemical properties regulate specific immune responses has become a vital requirement. Here we prepared poly(d,l-lactic-co-glycolic acid) (PLGA) nano/microparticles with uniform sizes (500 nm, 900 nm, 2.

Pathogen-Mimicking Polymeric Nanoparticles based on Dopamine Polymerization as Vaccines Adjuvants Induce Robust Humoral and Cellular Immune Responses.

Aiming to enhance the immunogenicity of subunit vaccines, a novel antigen delivery and adjuvant system based on dopamine polymerization on the surface of poly(D,L-lactic-glycolic-acid) nanoparticles (NPs) with multiple mechanisms of immunity enhancement is developed. The mussel-inspired biomimetic polydopamine (pD) not only serves as a coating to NPs but also functionalizes NP surfaces. The method is facile and mild including simple incubation of the preformed NPs in the weak alkaline dopamine solution, and incorporation of hepatitis B surface antigen and TLR9 agonist unmethylated cytosine-guanine (CpG) motif with the pD surface.

Improving the solubility of dexlansoprazole by cocrystallization with isonicotinamide.

Cocrystallization of an active pharmaceutical ingredient (API) with a cocrystal former (co-former) is widely used to tailor the physicochemical properties of parent APIs. For proton-pump inhibitors (PPIs), the isolation of cocrystals has not been widely investigated. Here, a 1:1 cocrystal of a PPI molecule, dexlansoprazole (DLS), was obtained by solvent crystallization with isonicotinamide (INM).

Immunopotentiator-Loaded Polymeric Microparticles as Robust Adjuvant to Improve Vaccine Efficacy.

Purpose: Adjuvants are required to ensure the efficacy of subunit vaccines. Incorporating molecular immunopotentiators within particles could overcome drawbacks of molecular adjuvants (such as solubility and toxicity), and improve adjuvanticity of particles, achieving stronger adjuvant activity. Aim of this study is to evaluate the adjuvanticity of immunopotentiator-loaded polymeric particles for subunit vaccine.

pH-Responsive Poly(D,L-lactic-co-glycolic acid) Nanoparticles with Rapid Antigen Release Behavior Promote Immune Response.

In the quest to treat intracellular infectious diseases and virus infection, nanoparticles (NPs) have been considered to be efficient tools for inducing potent immune responses, specifically cellular immunity. Antigen processing and presenting by antigen presenting cells (APCs) could influence immune response, especially the priming of T-cell-mediated cellular immunity. Here, we fabricated pH-responsive poly(D,L-lactic-co-glycolic acid) (PLGA) NPs with rapid antigen intracellular release behavior in APCs.

Particle design of membrane emulsification for protein drug and vaccine delivery.

Biodegradable particles have important applications in Drug Delivery Systems (DDS) of protein/peptide drugs. And recently, particle systems have also showed to be powerful for vaccine delivery (adjuvant) in order to solve the difficulties when conventional Alum adjuvant was used. However, in above applications, the problems of broad size distribution and poor reproducibility of particles, and deactivation of protein during the preparation, storage and release, are still big challenges.