SELP Copolymers for Selective Tumor Embolization
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Solution Overview
Problem
Current embolizing agents for treating hepatocellular carcinoma (HCC) face challenges such as non-selective delivery, collateral damage to healthy liver tissue, and inability to effectively deliver high-molecular-weight chemotherapeutics, leading to limited treatment options and recurrence of tumors due to permanent blockage and off-target effects.
Innovation Solution
Development of silk-elastin-like protein (SELP) copolymers that transition from a liquid to a hydrogel at body temperature, forming a stable occlusion in tumor vasculature while allowing controlled release of chemotherapeutics, and are biodegradable to enable repeated treatments and minimize collateral damage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If permanent blockage is used to embolize tumor vasculature, then embolization durability is improved, but recanalization and tumor regrowth occur leading to limited treatment options
Solution Approach 1:
The patent applies parameter changes by controlling the degradation rate of the biodegradable polymer embolic agent. By adjusting polymer composition, molecular weight, and crosslinking density, the embolization duration can be tuned from temporary to semi-permanent, allowing repeat treatments after degradation while maintaining initial embolization efficacy
Solution Approach 2:
The patent employs biodegradable polymer embolic agents that temporarily block vasculature and then degrade, functioning as disposable embolic materials. This allows the vasculature to recover and be re-treated if necessary, contrasting with permanent non-degradable embolics
2Quantity of substance
If high-molecular-weight chemotherapeutics are delivered, then treatment efficacy is improved, but delivery capability is limited by current embolizing agents
Solution Approach 1:
The patent utilizes porous microsphere structures with controlled pore sizes and distributions that can accommodate high-molecular-weight chemotherapeutics. The porous architecture allows drug loading, retention, and controlled release while maintaining structural integrity for embolization
Solution Approach 2:
The patent creates composite embolic agents combining biodegradable polymer matrices with chemotherapeutic drugs, contrast agents, and functional modifiers. This composite approach enables simultaneous embolization, drug delivery, and imaging capabilities
3Quantity of substance
If non-selective delivery is used for embolization, then embolization coverage is improved, but collateral damage to healthy liver tissue occurs
Solution Approach 1:
The patent applies local quality by incorporating tumor-specific targeting ligands (antibodies, peptides, aptamers) onto the embolic agent surface. These ligands selectively bind to receptors overexpressed on tumor vasculature, directing embolization to tumor tissue while sparing healthy liver parenchyma
4Adaptability or versatility
If off-target effects occur from current embolizing agents, then treatment breadth is improved, but systemic toxicity increases
Solution Approach 1:
The patent uses biodegradable polymer intermediaries that temporarily carry chemotherapeutics through the bloodstream to the tumor site. The polymers protect drugs from premature degradation and off-target release, then degrade at the target site to release drugs locally, reducing systemic exposure and toxicity
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
SELP copolymers provide selective and controlled embolization and drug delivery, reducing collateral damage and enabling repeated treatments, while allowing for sustained drug release and biodegradation, thus improving treatment outcomes for HCC by targeting tumors more precisely and minimizing systemic toxicity.
Implementation Method 1
The SELP solution is an injectable liquid at room temperature and forms a hydrogel in the tumor vasculature at body temperature
Implementation Method 2
The copolymers may also have matrix metalloprotease cleavage sites engineered into the protein copolymer using recombinant techniques to enable controlled breakdown of the embolic material
Implementation Method 3
The hydrogel may be configured to release chemotherapeutic drug into the tumor at a defined rate
Data Source
AI summary
A chemoembolic agent is disclosed that includes an injectable, recombinantly synthesized silk-elastin like protein copolymer and one or more chemotherapeutic agents. Upon injection, the chemoembolic agent blocks the tumor vasculature, including the capillary bed, and may optionally release chemotherapeutic agents. The chemoembolic agent may be used to treat cancer, including hepatocellular carcinoma.