Browse
Submit Data
Databases
API
Help

Dataset Information

39 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Improving STING Agonist Delivery for Cancer Immunotherapy Using Biodegradable Mesoporous Silica Nanoparticles.

ABSTRACT: Stimulator of interferon genes (STING) activation by intratumoral STING agonist treatment has been recently shown to eradicate tumors in preclinical models of cancer immunotherapy, generating intense research interest and leading to multiple clinical trials. However, there are many challenges associated with STING agonist-based cancer immunotherapy, including low cellular uptake of STING agonists. Here, biodegradable mesoporous silica nanoparticles (bMSN) with an average size of 80 nm are developed for efficient cellular delivery of STING agonists. STING agonists delivered via bMSN potently activate innate and adaptive immune cells, leading to strong antitumor efficacy and prolonged animal survival in murine models of melanoma. Delivery of immunotherapeutic agents via biodegradable bMSN is a promising approach for improving cancer immunotherapy.

SUBMITTER: Park KS

PROVIDER: S-EPMC8294168 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Improving STING Agonist Delivery for Cancer Immunotherapy Using Biodegradable Mesoporous Silica Nanoparticles.

Park Kyung Soo KS Xu Cheng C Sun Xiaoqi X Louttit Cameron C Moon James J JJ

Advanced therapeutics 20200721 10

Stimulator of interferon genes (STING) activation by intratumoral STING agonist treatment has been recently shown to eradicate tumors in preclinical models of cancer immunotherapy, generating intense research interest and leading to multiple clinical trials. However, there are many challenges associated with STING agonist-based cancer immunotherapy, including low cellular uptake of STING agonists. Here, biodegradable mesoporous silica nanoparticles (bMSN) with an average size of 80 nm are develo ...[more]

PMID: 34295963

Similar Datasets

Biodegradable STING agonist nanoparticles for enhanced cancer immunotherapy.

Project description:Therapeutic cancer vaccines require adjuvants leading to robust type I interferon and proinflammatory cytokine responses in the tumor microenvironment to induce an anti-tumor response. Cyclic dinucleotides (CDNs), a potent Stimulator of Interferon Receptor (STING) agonist, are currently in phase I trials. However, their efficacy may be limited to micromolar concentrations due to the cytosolic residence of STING in the ER membrane. Here we utilized biodegradable, poly(beta-amino ester) (PBAE) nanoparticles to deliver CDNs to the cytosol leading to robust immune response at >100-fold lower extracellular CDN concentrations in vitro. The leading CDN PBAE nanoparticle formulation induced a log-fold improvement in potency in treating established B16 melanoma tumors in vivo when combined with PD-1 blocking antibody in comparison to free CDN without nanoparticles. This nanoparticle-mediated cytosolic delivery method for STING agonists synergizes with checkpoint inhibitors and has strong potential for enhanced cancer immunotherapy.

| S-EPMC6035751 | biostudies-literature

Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles

Project description:In the present study, we designed a nanoscale platform for the sustained and controlled delivery of nutrients to pancreatic islets-upon transplantation. Our platform consists of a mesoporous silica nanoparticle (MSNP), loaded with glutamine (G), an essential amino acid required for islet survival and function, and capped with polydopamine (PD). To control the release of glutamine, various concentrations (0.5 - 2 mg/mL) of PD and incubation times (0.5 – 2 h) with MSNPs were investigated in terms of pharmacological properties and biological functions. After extensive testing, PD-G-MSNPs made using PD coating of 0.5 mg/mL incubated for 0.5 h resulted in the optimal platform to maintain the islet viability and functionality in vitro. Following syngeneic renal sub-capsule islet transplantation in STZ-diabetic mice, PD-G-MSNPs improved the engraftment of pancreatic islets as well as their function, resulting in re-establishment of glycemic control. Collectively, our data shows that PD-G-MSNPs can support transplanted islets by providing them with a controlled and sustained supply of nutrients.

2023-12-04 | GSE247020 | GEO

Positron Emission Tomography-Guided Photodynamic Therapy with Biodegradable Mesoporous Silica Nanoparticles for Personalized Cancer Immunotherapy.

Project description:Photodynamic therapy (PDT) is an effective, noninvasive therapeutic modality against local tumors that are accessible to the source of light. However, it remains challenging to apply PDT for the treatment of disseminated, metastatic cancer. On the other hand, cancer immunotherapy offers a promising approach for generating systemic antitumor immune responses against disseminated cancer. Here we report a multifunctional nanomaterial system for the combination of PDT and personalized cancer immunotherapy and demonstrate their potency against local as well as disseminated tumors. Specifically, we have synthesized uniform and biodegradable mesoporous silica nanoparticles (bMSN) with an average size of ∼80 nm and large pore size of 5-10 nm for theranostic positron emission tomography (PET)-guided PDT and neoantigen-based cancer vaccination. Multiple neoantigen peptides, CpG oligodeoxynucleotide adjuvant, and photosensitizer chlorin e6 were coloaded into a bMSN nanoplatform, and PET imaging revealed effective accumulation of bMSN in tumors (up to 9.0% ID/g) after intravenous administration. Subsequent PDT with laser irradiation recruited dendritic cells to PDT-treated tumor sites and elicited neoantigen-specific, tumor-infiltrating cytotoxic T-cell lymphocytes. Using multiple murine models of bilateral tumors, we demonstrate strong antitumor efficacy of PDT-immunotherapy against locally treated tumors as well as distant, untreated tumors. Our findings suggest that the bMSN is a promising platform for combining imaging and PDT-enhanced personalized immunotherapy for the treatment of advanced cancer.

| S-EPMC6832743 | biostudies-literature

Targeted delivery of a STING agonist to brain tumors using bioengineered protein nanoparticles for enhanced immunotherapy.

Project description:Immunotherapy is emerging as a powerful tool for combating many human diseases. However, the application of this life-saving treatment in serious brain diseases, including glioma, is greatly restricted. The major obstacle is the lack of effective technologies for transporting therapeutic agents across the blood-brain barrier (BBB) and achieving targeted delivery to specific cells once across the BBB. Ferritin, an iron storage protein, traverses the BBB via receptor-mediated transcytosis by binding to transferrin receptor 1 (TfR1) overexpressed on BBB endothelial cells. Here, we developed bioengineered ferritin nanoparticles as drug delivery carriers that enable the targeted delivery of a small-molecule immunomodulator to achieve enhanced immunotherapeutic efficacy in an orthotopic glioma-bearing mouse model. We fused different glioma-targeting moieties on self-assembled ferritin nanoparticles via genetic engineering, and RGE fusion protein nanoparticles (RGE-HFn NPs) were identified as the best candidate. Furthermore, RGE-HFn NPs encapsulating a stimulator of interferon genes (STING) agonist (SR717@RGE-HFn NPs) maintained stable self-assembled structure and targeting properties even after traversing the BBB. In the glioma-bearing mouse model, SR717@RGE-HFn NPs elicited a potent local innate immune response in the tumor microenvironment, resulting in significant tumor growth inhibition and prolonged survival. Overall, this biomimetic brain delivery platform offers new opportunities to overcome the BBB and provides a promising approach for brain drug delivery and immunotherapy in patients with glioma.

| S-EPMC8965725 | biostudies-literature

Biodegradable Nanoparticles Induce cGAS/STING-dependent Reprogramming of Myeloid Cells to Promote Tumor Immunotherapy

Project description:Spleens were collected from C57BL/6 mice that were treated with (1) saline, (2) a single dose of nanoparticles, (3) 3 doses of nanoparticles administered daily, or (4) 3 doses of nanoparticles administered every 3 days. Single-cell RNA-sequencing was conducted using the 10X Genomics platform and analyzed with Seurat.

2023-03-09 | E-MTAB-11584 | biostudies-arrayexpress

Optimized Fabrication of Dendritic Mesoporous Silica Nanoparticles as Efficient Delivery System for Cancer Immunotherapy.

Project description:In the past decade, cancer immunotherapy has revolutionized the field of oncology. Major immunotherapy approaches such as immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, cytokines, and immunomodulators have shown great promise in preclinical and clinical settings. Among them, immunomodulatory agents including cancer vaccines are particularly appealing; however, they face limitations, notably the absence of efficient and precise targeted delivery of immune-modulatory agents to specific immune cells and the potential for off-target toxicity. Nanomaterials can play a pivotal role in addressing targeting and other challenges in cancer immunotherapy. Dendritic mesoporous silica nanoparticles (DMSNs) can enhance the efficacy of cancer vaccines by enhancing the effective loading of immune modulatory agents owing to their tunable pore sizes. In this work, an emulsion-based method is optimized to customize the pore size of DMSNs and loaded DMSNs with ovalbumin (OVA) and cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (CpG-OVA-DMSNs). The immunotherapeutic effect of DMSNs is achieved through controlled chemical release of OVA and CpG in antigen-presenting cells (APCs). The results demonstrated that CpG-OVA-DMSNs efficiently activated the immune response in APCs and reduced tumor growth in the murine B16-OVA tumor model.

| S-EPMC11636195 | biostudies-literature

Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles

Project description:Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles

| PRJNA1035764 | ENA

Controlled Nutrient Delivery to Pancreatic Islets Using Polydopamine-Coated Mesoporous Silica Nanoparticles.

Project description:In the present study, we created a nanoscale platform that can deliver nutrients to pancreatic islets in a controlled manner. Our platform consists of a mesoporous silica nanoparticle (MSNP), which can be loaded with glutamine (G: an essential amino acid required for islet survival and function). To control the release of G, MSNPs were coated with a polydopamine (PD) layer. With the optimal parameters (0.5 mg/mL and 0.5 h), MSNPs were coated with a layer of PD, which resulted in a delay of G release from MSNPs over 14 d (57.4 ± 4.7% release). Following syngeneic renal subcapsule islet transplantation in diabetic mice, PDG-MSNPs improved the engraftment of islets (i.e., enhanced revascularization and reduced inflammation) as well as their function, resulting in re-establishment of glycemic control. Collectively, our data show that PDG-MSNPs can support transplanted islets by providing them with a controlled and sustained supply of nutrients.

| S-EPMC8121116 | biostudies-literature

Particle-Size-Dependent Delivery of Antitumoral miRNA Using Targeted Mesoporous Silica Nanoparticles.

Project description:Multifunctional core-shell mesoporous silica nanoparticles (MSN) were tailored in size ranging from 60 to 160 nm as delivery agents for antitumoral microRNA (miRNA). The positively charged particle core with a pore diameter of about 5 nm and a stellate pore morphology allowed for an internal, protective adsorption of the fragile miRNA cargo. A negatively charged particle surface enabled the association of a deliberately designed block copolymer with the MSN shell by charge-matching, simultaneously acting as a capping as well as endosomal release agent. Furthermore, the copolymer was functionalized with the peptide ligand GE11 targeting the epidermal growth factor receptor, EGFR. These multifunctional nanoparticles showed an enhanced uptake into EGFR-overexpressing T24 bladder cancer cells through receptor-mediated cellular internalization. A luciferase gene knock-down of up to 65% and additional antitumoral effects such as a decreased cell migration as well as changes in cell cycle were observed. We demonstrate that nanoparticles with a diameter of 160 nm show the fastest cellular internalization after a very short incubation time of 45 min and produce the highest level of gene knock-down.

| S-EPMC7355705 | biostudies-literature

Tumor-targeted delivery of a STING agonist improvescancer immunotherapy.

Project description:The cGAS-STING pathway is essential for immune defense against microbial pathogens and malignant cells; as such, STING is an attractive target for cancer immunotherapy. However, systemic administration of STING agonists poses safety issues while intratumoral injection is limited by tumor accessibility. Here, we generated antibody-drug conjugates (ADCs) by conjugating a STING agonist through a cleavable linker to antibodies targeting tumor cells. Systemic administration of these ADCs was well tolerated and exhibited potent antitumor efficacy in syngeneic mouse tumor models. The STING ADC further synergized with an anti-PD-L1 antibody to achieve superior antitumor efficacy. The STING ADC promoted multiple aspects of innate and adaptive antitumor immune responses, including activation of dendritic cells, T cells, natural killer cells and natural killer T cells, as well as promotion of M2 to M1 polarization of tumor-associated macrophages. These results provided the proof of concept for clinical development of the STING ADCs.

| S-EPMC9894229 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data