Embolization Particles with Metal Oxide Nanoparticles for Deep Tumor Treatment
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Solution Overview
Problem
Current cancer treatment methods, such as radiotherapy and photodynamic therapy, face limitations in penetrating deep tissues and are ineffective against hypoxic tumor cells, while embolization techniques struggle to simultaneously occlude blood vessels and deliver radiotherapeutic agents effectively.
Innovation Solution
Development of multimodal embolization particles coated with metal oxide nanoparticles doped with rare earth elements, specifically titanium dioxide, zinc oxide, or cerium dioxide, which can be excited by X-ray or proton beam radiation to generate reactive oxygen species (ROS) under both normoxic and hypoxic conditions, allowing for simultaneous embolization and radiotherapeutic treatment of tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Illumination intensity
If photodynamic therapy is used to treat cancer, then superficial cancers can be treated with photosensitizing agents and light exposure, but the treatment cannot penetrate deep into the body and is limited to superficial cancers
Solution Approach 1:
The patent combines embolization particles with metal oxide nanoparticles into a single multimodal particle system. The embolization component occludes blood vessels while the metal oxide nanoparticles generate ROS under X-ray or proton beam radiation, integrating two therapeutic functions into one particle that can treat deep-seated tumors effectively
Solution Approach 2:
The patent replaces the light-based activation mechanism of photodynamic therapy with X-ray or proton beam radiation activation. This substitution enables deeper tissue penetration since ionizing radiation can reach deep tumors, and the metal oxide nanoparticles convert this radiation energy into ROS for therapeutic effect
2Reliability
If radiotherapy is used to treat radioresistant cancers such as renal cell cancer, then high doses of radiation are required to destroy the cancer, but these high doses increase the risk of causing cancer and are too high to be safe in clinical practice
Solution Approach 1:
The patent creates localized ROS generation at the tumor site through metal oxide nanoparticles that are selectively delivered via embolization. The ROS are generated only where the nanoparticles accumulate in the tumor vasculature and are activated by targeted X-ray or proton beam radiation, concentrating the therapeutic effect locally while minimizing exposure to healthy tissues
Solution Approach 2:
The metal oxide nanoparticles act as intermediaries that convert X-ray or proton beam radiation energy into reactive oxygen species. This intermediary mechanism allows the use of lower doses of ionizing radiation compared to conventional radiotherapy, as the nanoparticles amplify the biological effect through ROS generation, thereby reducing the harmful effects of high-dose radiation
3Reliability
If conventional embolization particles are used to occlude blood vessels, then blood flow to the tumor is restricted, but the particles cannot simultaneously generate radiotherapeutic effects under hypoxic conditions
Solution Approach 1:
The patent merges embolization particles with metal oxide nanoparticles to create a single multimodal particle that performs both embolization and radiotherapeutic functions. The embolization component occludes tumor blood vessels while the metal oxide nanoparticles provide ROS generation capability under X-ray or proton beam radiation, including under hypoxic conditions where conventional radiotherapy fails
Solution Approach 2:
The multimodal embolization particle with metal oxide nanoparticles serves multiple functions: it embolizes tumor vasculature to restrict blood flow, delivers metal oxide nanoparticles to the tumor site, and generates ROS under X-ray or proton beam radiation even under hypoxic conditions. This multi-functionality overcomes the limitations of conventional single-function embolization particles
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
The embolization particles effectively occlude tumor vasculature and generate ROS to treat cancer cells under hypoxic conditions, enhancing the efficacy of radiotherapy and improving treatment outcomes by combining embolization with radiotherapeutic effects.
Implementation Method 1
nanoparticles which comprise a metal oxide doped with one or more rare earth elements, wherein the metal oxide is titanium dioxide, zinc oxide or cerium dioxide... can be excited by X-ray or proton beam radiation to generate reactive oxygen species (ROS)
Implementation Method 2
The agent is absorbed by cells all over the body, but it generally accumulates in the tumour due to abnormalities or defects in the tumour vasculature. It is also rapidly absorbed by cancer cells, which tend to grow and divide much more quickly than healthy cells and hence have a higher metabolic activity.
Implementation Method 3
The photosensitizing agent that has accumulated in the tumour is excited by exposure to this light and reacts with nearby oxygen or water molecules in the tissue to produce reactive oxygen species (ROS), such as singlet oxygen... a superoxide radical... or a hydroxyl radical
Implementation Method 4
It is believed that the titanium dioxide particles produce hydroxyl radicals that oxidize the membrane lipids of the cells to produce peroxidants, which then set up a series of peroxidant chain reactions. The oxidatively stressed malignant cells progress to a necrotic state that results in their destruction.
Data Source
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AI summary
The present invention relates to an embolization particle comprising a microparticle coated with a plurality of nanoparticles, which nanoparticles comprise a metal oxide doped with one or more rare earth elements, wherein the metal oxide is titanium dioxide, zinc oxide or cerium dioxide. An embolization particle of the invention for use in the treatment of cancer in combination with X-ray radiation or proton beam radiation, or use in embolization, is also described. The invention also relates to a process for producing an embolization particle comprising a microparticle coated with a plurality of nanoparticles, which nanoparticles comprise a metal oxide doped with one or more rare earth elements, wherein the metal oxide is titanium dioxide, zinc oxide or cerium dioxide, which process comprises: (i) providing a microparticle; (ii) contacting the microparticle with a plurality of the nanoparticles; and (iii) heating the microparticle and the nanoparticles to form the embolization particle.