Depolymerized Crosslinked Hyaluronan Suppresses Cancer Growth
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
High molecular weight hyaluronan promotes cancer cell growth, while small fragments increase angiogenesis and tumor cell migration, necessitating a solution to suppress cancer cell growth effectively.
Innovation Solution
Depolymerized and crosslinked hyaluronan, prepared by sonicating high molecular weight hyaluronan under specific conditions, is used to suppress cancer cell growth by contacting cancer cells, with at least 90% of the depolymerized hyaluronan having a molecular weight ranging from 100-500 kDa and containing inter-chain covalent crosslinks at a level of 25% or higher.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If high molecular weight hyaluronan is used, then anti-angiogenic and anti-inflammatory effects are achieved, but it promotes cancer cell growth
Solution Approach 1:
The patent applies segmentation by depolymerizing high molecular weight hyaluronan into smaller fragments with molecular weights of 100-500 kDa through sonication. This segmentation transforms the harmful high molecular weight HA that promotes cancer growth into beneficial low molecular weight fragments that suppress cancer cell growth while retaining anti-angiogenic properties.
Solution Approach 2:
The patent changes the molecular weight parameter of hyaluronan from millions of daltons (high molecular weight) to 100-500 kDa (depolymerized). This parameter change fundamentally alters the biological activity, converting HA from a cancer-promoting substance to a cancer-suppressing agent that binds to Hyal-2 receptor.
2Reliability
If hyaluronan is depolymerized to suppress cancer cell growth, then anti-cancer effect is achieved, but manufacturing precision control becomes challenging
Solution Approach 1:
The patent employs periodic action through controlled sonication treatment with specific parameters (20-80 kHz frequency, 3-6 hours duration, 50-80°C temperature). This periodic mechanical energy input progressively depolymerizes hyaluronan to achieve the target molecular weight range of 100-500 kDa, providing reproducible manufacturing control.
Solution Approach 2:
The patent implements feedback control by monitoring molecular weight during sonication and adjusting treatment parameters accordingly. By measuring the molecular weight of depolymerized HA and comparing it to the target range (100-500 kDa), the sonication process can be optimized to achieve consistent product quality with at least 90% of molecules in the desired range.
3Reliability
If depolymerized hyaluronan is used to suppress cancer cell growth, then anti-cancer efficacy is improved, but the mechanism of action remains unclear
Solution Approach 1:
The patent identifies Hyal-2 as the intermediary mediator between depolymerized hyaluronan and cancer cells. The 100-500 kDa HA fragments bind to Hyal-2 receptor on cell surfaces, triggering anti-cancer signaling pathways. This intermediary mechanism explains how depolymerized HA suppresses cancer cell growth, angiogenesis, and metastasis while providing potential therapeutic targets.
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 depolymerized and crosslinked hyaluronan significantly suppresses cancer cell growth in mouse models, demonstrating potential as an anti-cancer agent for treating various types of cancers, including breast cancer, melanoma, and glioblastoma, by potentially binding to Hyal-2, a cell membrane anchor protein.
Implementation Method 1
High molecular weight HA molecules can be degraded via enzymatic, chemical, or physical methods to produce depolymerized HA products
Implementation Method 2
High molecular weight HA molecules can be degraded via enzymatic, chemical, or physical methods to produce depolymerized HA products
Implementation Method 3
The sonication can be carried out at about 20-80 kHz (e.g., 50-60 kHz) for about 3-6 hours. Alternatively or in addition, it can be carried out under a temperature ranging from about 50 - 80 °C (e.g., 65 to 70 °C)
Data Source
AI summary
Uses of depolymerized hyaluronan (e.g., prepared by sonicating high molecular weight hyaluronan such as naturally-occurring hyaluronan) or anti-Hyal-2 antibody in cancer treatment. Also described herein are methods for preparing depolymerized and crosslinked hyaluronan by sonication and the hyaluronan composition thus obtained.