ArticleJournal for immunotherapy of cancer2021
Mesoporous silica nanoparticles inflame tumors to overcome anti-PD-1 resistance through TLR4-NFκB axis.
Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Tumor-Intrinsic ARHGEF3 Enhances Antitumor Immunity by Promoting T-Cell Infiltration and Limiting Myeloid Cell-Mediated Immunosuppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Heterogeneity of macrophages in PD-1/PD-L1 inhibitor therapy: a single-cell perspective.Cellular & molecular biology letters · 2026Review
- Size-Dependent Immunomodulatory Effects of FeMolecules (Basel, Switzerland) · 2026Article
- Iron Oxide Nanoparticles Induce Macrophage Secretion of ATP and HMGB1 to Enhance Irradiation-Led Immunogenic Cell Death.Bioconjugate chemistry · 2025Article
- Nanoparticulated Anti-Programmed Cell Death-1 Antibody Improves Localized Immune Checkpoint Blockade Therapy.Biomaterials research · 2025Article
- Mesoporous silica nanoparticles--based functional platforms for breast cancer therapy: technological advancements.Frontiers in chemistry · 2025Review
- Targeting tumor-draining lymph node to overcome resistance to cancer immunotherapy: an update.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Utilizing Nanoparticles to Overcome Anti-PD-1/PD-L1 Immunotherapy Resistance in Non-Small Cell Lung cancer: A Potential Strategy.International journal of nanomedicine · 2025Review
- Engineered nanoparticles for precise targeted drug delivery and enhanced therapeutic efficacy in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2024Review
- Adjuvant Novel Nanocarrier-Based Targeted Therapy for Lung Cancer.Molecules (Basel, Switzerland) · 2024Review
- Leukemic cell-secreted interleukin-9 suppresses cytotoxic T cell-mediated killing in chronic lymphocytic leukemia.Cell death & disease · 2024Article
- Leveraging mesoporous silica nanomaterial for optimal immunotherapeutics against cancer.In vitro models · 2023Review
- Thiolated Mesoporous Silica Nanoparticles as an Immunoadjuvant to Enhance Efficacy of Intravesical Chemotherapy for Bladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Recent applications of immunomodulatory biomaterials for disease immunotherapy.Exploration (Beijing, China) · 2022Review
- Immunotherapeutic Implications of Toll-like Receptors Activation in Tumor Microenvironment.Pharmaceutics · 2022Review
- Mechanisms of tumor resistance to immune checkpoint blockade and combination strategies to overcome resistance.Frontiers in immunology · 2022Review
- Differential Expression of theFrontiers in cell and developmental biology · 2021Article
- Emerging Nano-Based Strategies Against Drug Resistance in Tumor Chemotherapy.Frontiers in bioengineering and biotechnology · 2021Review
- Self-Therapeutic Nanomaterials: Applications in Biology and Medicine.Materials today (Kidlington, England)Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe clinical benefits of antiprogrammed cell death protein 1 (PD-1) therapy are compromised by resistance in immunologically cold tumors. Convergence of immunotherapy and bioengineering is potential to overcome the resistance. Mesoporous silica nanoparticles (MSNs) are considered the most promising inorganic biological nanomaterials for clinical transformation, however, the fundamental influence of MSNs on immunotherapy is unclear. In this study, we aimed to investigate the role of MSNs in tumor resensitization and explore the feasibility of MSNs combined with anti-PD-1 in cancer therapy.
methodsIntrinsic and acquired resistant tumors, as well as spontaneous and secondary tumor recurrence models, were used to evaluate the influence of MSNs and the synergistical effect with anti-PD-1 therapy. The roles of CD8
resultsBoth granular and rod-shaped MSNs efficiently overcame tumor resistance with dependence on diameter and aspect ratio. Only once injection of MSNs in prior to anti-PD-1 markedly improved the treatment efficacy, protective immunity, and prognosis. MSNs per se boosted infiltration of CTLs as the early event (days 2-3); and synergistically with anti-PD-1 therapy, MSNs rapidly established a T cell-inflamed microenvironment with abundant high-activated (interferon-γ/tumor necrosis factor-α/Perforin/GranzymeB) and low-exhausted (PD-1/lymphocyte-activation gene 3 (LAG-3)/T-cell immunoglobulin and mucin-domain containing-3 (TIM-3)) CTLs. Chemokines Ccl5/Cxcl9/Cxcl10, which were produced predominantly by macrophages, promoted MSNs-induced CTLs infiltration. MSNs led to high Ccl5/Cxcl9/Cxcl10 production in vitro and in mice through regulating TLR4-NFκB axis. Blocking TLR4-NFκB axis in macrophages or CTLs infiltration abrogated MSNs-induced resensitization to anti-PD-1 therapy.
conclusionsMSNs efficiently and rapidly inflame immunologically cold tumors and resensitize them to anti-PD-1 therapy through TLR4-NFκB-Ccl5/Cxcl9/Cxcl10 axis. MSNs-based theranostic agents can serve as sensitizers for patients with resistant tumors to improve immunotherapy.
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