Prussian Blue Nanoparticles for Immune Checkpoint Resistant Cancer
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Solution Overview
Problem
Current photothermal therapy for immune checkpoint resistant cancers is ineffective in preventing cancer relapse due to limitations in the design of photothermal therapy agents and rapid clearance of immune adjuvants, leading to incomplete tumor eradication and treatment resistance.
Innovation Solution
Combining photothermal therapy using uncoated or functionalized Prussian blue nanoparticles (PBNPs) with CD137 agonists to enhance immune response, where PBNPs are biofunctionalized with a biocompatible coating and biomolecules like CD137 agonists to prolong bioavailability and induce immunogenic cell death.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If photothermal therapy is used to ablate tumor, then most of the tumor is destroyed, but the tumor is not completely eradicated and relapse occurs
Solution Approach 1:
The patent combines photothermal therapy (PTT) with immune adjuvant therapy into a single integrated treatment approach. PBNPs are functionalized with immune adjuvants (anti-PD-1, anti-CTLA-4, or anti-LAG-3 antibodies), allowing simultaneous photothermal ablation and immune system activation. This merging addresses the incompleteness of PTT alone by adding an immune-mediated elimination mechanism that targets residual tumor cells, thereby preventing relapse while maintaining effective tumor destruction.
Solution Approach 2:
The patent creates composite nanomaterials consisting of Prussian blue nanoparticle cores functionalized with immune adjuvant molecules. These composite structures integrate the photothermal conversion capability of PBNPs with the immunomodulatory functions of checkpoint inhibitors. The composite design enables dual functionality: photothermal heating for direct tumor cell ablation and immune adjuvant release for systemic anti-tumor immunity, achieving complete tumor eradication and relapse prevention.
2Reliability
If immune adjuvants are administered directly into bloodstream or injected into tissue, then immune response is activated, but they are rapidly cleared before eliciting full response
Solution Approach 1:
The patent applies preliminary action by pre-functionalizing PBNPs with immune adjuvants before administration. The adjuvants are already attached to the nanoparticle carrier, which protects them from premature clearance. Upon photothermal activation, the adjuvants are released at the tumor site in a controlled manner, ensuring sustained presence and full immune response activation. This preliminary loading strategy prevents rapid clearance and maximizes therapeutic efficacy.
Solution Approach 2:
The PBNP serves as an intermediary carrier that mediates between the immune adjuvant and the biological system. The nanoparticle protects the adjuvant from rapid clearance by the reticuloendothelial system while delivering it to the tumor microenvironment. This intermediary approach extends the bioavailability time of the adjuvant and ensures sustained immune response activation, overcoming the limitation of direct administration.
3Reliability
If current photothermal therapy agents are used, then tumor ablation is achieved, but they do not engage immunogenic cell death or utilize immune adjuvants
Solution Approach 1:
The patent implements multi-functionality by designing PBNPs that simultaneously perform photothermal tumor ablation and immune system activation. The functionalized nanoparticles serve multiple roles: photothermal agents for heat generation, drug carriers for immune adjuvant delivery, and immunomodulators for checkpoint inhibition. This universal design overcomes the limitation of conventional single-function PTT agents and enables comprehensive cancer treatment through combined thermal and immunological mechanisms.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This combination significantly improves treatment efficacy by prolonging bioavailability, engaging immunogenic cell death, and achieving a robust abscopal effect, effectively preventing cancer recurrence and metastasis in immune checkpoint inhibitor-resistant cancers.
Implementation Method 1
photothermal therapy using either uncoated or functionalized Prussian blue nanoparticles (PBNPs)
Data Source
AI summary
Embodiments of the instant disclosure relate to novel methods and compositions for treating tumors resistant to immune checkpoint inhibitors. In certain embodiments, compositions herein can have at least one nanoparticle formed of Prussian blue materials and, optionally, one or more CD137 agonists. In other embodiments, methods of treating tumors herein can include administering an effective amount of at least photothermal therapy agent in combination with at least one CD137 agonist separately or in a combination therapy/combination composition.