CCR2-Targeting Copper Nanocluster for Pancreatic Cancer Therapy
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Solution Overview
Problem
Current cancer therapies, including chemotherapy and immunotherapy, are ineffective in treating pancreatic ductal adenocarcinoma (PDAC) due to the immunosuppressive tumor microenvironment created by CCR2+ stromal cells, which hinder the delivery and efficacy of treatments.
Innovation Solution
A CCR2-targeting composition comprising a CCR2 binding peptide, a chemotherapeutic agent, and a biodegradable copper nanocluster (CuNC) is developed, allowing specific delivery to CCR2+ cells within the tumor microenvironment, where the chemotherapeutic agent is released to kill immunosuppressive cells, thereby enhancing treatment efficacy and converting the microenvironment to an immunoresponsive state.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapy and immunotherapy are used to treat PDAC, then treatment is administered, but the treatment is ineffective due to the immunosuppressive tumor microenvironment created by CCR2+ stromal cells
Solution Approach 1:
The patent extracts and targets the harmful CCR2+ stromal cells from the tumor microenvironment using a CCR2-targeting composition. The composition specifically binds to CCR2 receptors on these immunosuppressive cells, allowing selective removal of the harmful factor while preserving the beneficial tumor microenvironment for immunotherapy efficacy.
Solution Approach 2:
The CCR2-targeting composition acts as an intermediary agent between the immunosuppressive CCR2+ cells and the therapeutic effect. This composition mediates the interaction by delivering chemotherapeutic agents or immunotherapeutic agents specifically to CCR2+ cells, converting the harmful immunosuppressive environment into a beneficial immunoresponsive state.
2Measurement precision
If CCR2-targeting composition is developed to specifically deliver chemotherapeutic agent to CCR2+ cells, then treatment specificity is improved, but device complexity increases
Solution Approach 1:
The CCR2-targeting composition is segmented into distinct functional components: a CCR2-binding peptide for target recognition, a chemotherapeutic agent moiety for cytotoxic effect, and optionally a nanoparticle carrier for delivery enhancement. This segmentation allows each component to be optimized independently while maintaining overall specificity.
Solution Approach 2:
The CCR2-targeting composition is designed with multi-functionality to reduce complexity. The same composition can deliver both chemotherapeutic agents and immunotherapeutic agents, and can be administered via multiple routes (IV, IP, IM, SC, IN, IT). This universal design achieves high delivery specificity without proportionally increasing complexity.
3Productivity
If the CCR2-targeting composition is used to eliminate CCR2+ myeloid cells, then tumor growth is inhibited, but the composition must be carefully designed to avoid off-target effects
Solution Approach 1:
The CCR2-targeting composition exhibits local quality by concentrating its therapeutic effect specifically at the tumor site where CCR2+ cells are present. The CCR2-binding peptide ensures the composition localizes to the tumor microenvironment rather than distributing systemically, thereby inhibiting tumor growth while minimizing off-target effects on healthy tissues.
Data Source
AI summary
The present disclosure reports a C-C chemokine type 2 receptor (CCR2) targeting mediated nanoimmunotherapy to treat cancer, such as pancreatic ductal adenocarcinoma (PDAC). Also disclosed herein is the use of a biodegradable copper nanocluster (CuNC) for enhanced loading of chemotherapeutic drug, such as Gemcitabine (Gem).