CD206-Targeted Dextran Compositions for M2-to-M1 Macrophage Repolarization
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Solution Overview
Problem
Cancer treatment is hindered by the immunosuppressive M2-like tumor-associated macrophages (TAMs) that suppress T-cells and promote tumor angiogenesis and metastases, necessitating a method to repolarize these macrophages to the more proinflammatory M1-like phenotype for enhanced therapeutic efficacy with reduced toxicity.
Innovation Solution
Compositions comprising a dextran backbone conjugated with CD206 targeting moieties and therapeutic agents like doxorubicin or Cu(II) ions are administered to repolarize M2-like TAMs to M1-like TAMs, potentially synergized with other therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If M2-like TAMs are present in tumors, then immunosuppression and promotion of tumor angiogenesis and metastases occur, but if M1-like TAMs are induced, then proinflammatory response and enhanced therapeutic efficacy are achieved
Solution Approach 1:
The patent changes the phenotypic state of macrophages from M2-like to M1-like through targeted delivery of therapeutic agents. This parameter change in macrophage activation state transforms their function from immunosuppressive to proinflammatory, thereby enhancing therapeutic efficacy while reducing harmful immunosuppression in the tumor microenvironment
Solution Approach 2:
The patent uses CD206-targeted delivery vehicles as intermediaries to deliver therapeutic agents specifically to macrophages. The CD206 targeting moiety acts as a mediator that recognizes and binds to CD206 receptors on macrophage surfaces, enabling selective delivery of therapeutics to repolarize M2-like TAMs to M1-like phenotype without affecting other cells
2Reliability
If conventional chemotherapy agents are administered, then tumor cell growth is inhibited, but toxicity to healthy tissues increases
Solution Approach 1:
The patent employs CD206-targeted delivery vehicles as intermediaries to bridge the gap between therapeutic agents and macrophages. The targeting moiety specifically recognizes CD206 receptors on macrophage surfaces, directing the therapeutic payload exclusively to macrophages while sparing healthy tissues, thereby maintaining treatment efficacy and reducing toxicity
Solution Approach 2:
The patent achieves local quality by concentrating the therapeutic effect specifically in macrophages within the tumor microenvironment. The CD206-targeted delivery system ensures that the therapeutic agent is delivered only to macrophages that express CD206, creating a localized therapeutic action that spares other healthy cells from exposure to the toxic effects of the therapeutic agent
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 method effectively repolarizes M2-like TAMs to M1-like TAMs, enhancing cancer treatment efficacy and reducing toxicity, and can be synergistically effective with other treatments.
Implementation Method 1
a dextran backbone and one or more CD206 targeting moieties conjugated thereto
Data Source
AI summary
Disclosed are methods and compositions for repolarizing a macrophage from M2 to M1 comprising administering to a subject in need thereof an effective dose of a compound comprising a dextran backbone and one or more CD206 targeting moieties conjugated thereto. In certain aspects, the compound further comprises a therapeutic agent selected from: paclitaxel, gemcitabine, lapatinib, and doxorubicin. In further aspect, the therapeutic agent comprises a chelator and at least one metal ion. In certain implementations, the at least one metal ion comprises at least one Cu(II) ions.