Related Experiment Video
Updated: Sep 29, 2025
Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
A pH-/Enzyme-Responsive Nanoparticle Selectively Targets Endosomal Toll-like Receptors to Potentiate Robust Cancer
Heming Xia1, Mengmeng Qin1, Zenghui Wang1
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
Abstract:
Toll-like receptor (TLR) agonists are potent immune-stimulators that hold great potential in vaccine adjuvants as well as cancer immunotherapy. However, TLR agonists in free form are prone to be eliminated quickly by the circulatory system and cause systemic inflammation side effects. It remains a challenge to achieve precise release of TLR7/8 agonist in the native form at the receptor site in the endosomal compartments while keeping stable encapsulation and inactive in nontarget environment. Here, we report a pH-/enzyme-responsive TLR7/8 agonist-conjugated nanovaccine (TNV), which responds intelligently to the acidic environment and cathepsin B in the endosome, precisely releases TLR7/8 agonist to activate its receptor signaling at the endosomal membrane, stimulates DCs maturation, and provokes specific cellular immunity. In vivo experiments demonstrate outstanding prophylactic and therapeutic efficacy of TNV in mouse melanoma and colon cancer. The endosome-targeted responsive nanoparticle strategy provides a potential delivery toolbox of adjuvants to advance the development of tumor nanovaccines.
Insights
This study introduces a novel nanovaccine that precisely delivers Toll-like receptor 7/8 (TLR7/8) agonists to cancer cells. This targeted approach enhances immune response and shows significant efficacy in preclinical cancer models.
Area of Science:
- Immunology
- Nanotechnology
- Oncology
Background:
- Toll-like receptor (TLR) agonists are potent immune stimulators with applications in cancer immunotherapy and vaccine adjuvants.
- Free TLR agonists face rapid clearance and systemic inflammation, posing delivery challenges.
- Achieving targeted, controlled release of TLR7/8 agonists in their native form within endosomes is crucial for efficacy and safety.
Purpose of the Study:
- To develop a pH- and enzyme-responsive nanovaccine for precise delivery of TLR7/8 agonists.
- To ensure stable encapsulation and targeted release within endosomal compartments.
- To evaluate the in vivo efficacy of the nanovaccine in cancer models.
Main Methods:
- Conjugation of a TLR7/8 agonist to a nanoparticle.
- Design of a nanovaccine responsive to endosomal pH and cathepsin B.
- In vivo studies using mouse melanoma and colon cancer models.
Main Results:
- The nanovaccine demonstrated intelligent response to endosomal acidic pH and cathepsin B.
- Precise release of TLR7/8 agonist activated receptor signaling and stimulated dendritic cell (DC) maturation.
- Outstanding prophylactic and therapeutic efficacy was observed in mouse melanoma and colon cancer models.
Conclusions:
- The developed nanovaccine strategy enables precise endosomal delivery of TLR7/8 agonists.
- This approach effectively stimulates specific cellular immunity and exhibits significant anti-cancer effects.
- Endosome-targeted responsive nanoparticles offer a promising delivery platform for cancer nanovaccines.
More Related Videos
Related Concept Videos
01:27Tumor Immunotherapy
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...