Biodegradable PD-L1 Polymer Conjugates for Tumor Delivery
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Solution Overview
Problem
Existing cancer treatments face challenges such as rapid drug elimination from tumors, poor response to immunotherapy due to low T cell infiltration, and accumulation of non-degradable polymer conjugates in organs, which impair biocompatibility and hinder effective chemotherapy and immunotherapy.
Innovation Solution
Development of biodegradable drug delivery conjugates with a single first cleavable peptide linker connecting two polymeric segments, covalently bonded to PD-L1 inhibitors, which enhance tumor targeting, induce immunogenic cell death, and promote PD-L1 degradation, thereby recruiting T cells and enhancing immunotherapy efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If nondegradable polymer components are used in drug delivery conjugates, then circulation time is prolonged and tumor accumulation is enhanced, but long-term accumulation in organs occurs impairing biocompatibility
Solution Approach 1:
The patent changes the chemical structure of polymer components from nondegradable to biodegradable forms, allowing the polymer to break down into smaller molecules that can be cleared by renal filtration, thus preventing long-term accumulation while maintaining circulation benefits
Solution Approach 2:
The polymer conjugate is designed with cleavable peptide linkers that segment the large polymer-drug complex into smaller components (polymer fragments and drug molecules) that can be independently cleared from the body, preventing accumulation
2Reliability
If small molecule drugs are used, then rapid clearance by glomerular filtration occurs, but tumor accumulation is insufficient
Solution Approach 1:
The patent creates composite polymer-drug conjugates where a hydrophilic polymer backbone is attached to hydrophobic anticancer drug molecules, combining the benefits of enhanced circulation and tumor accumulation with controlled clearance mechanisms
3Reliability
If PD-L1 inhibitors are used alone, then T cell activation is blocked, but tumors lacking T cell infiltration respond poorly to immunotherapy
Solution Approach 1:
The patent merges chemotherapy (using anticancer agents like epirubicin) with immunotherapy (using PD-L1 inhibitors) into a single conjugate system, where the chemotherapeutic component induces immunogenic cell death that releases tumor antigens, making previously cold tumors hot and responsive to PD-L1 blockade
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 conjugates effectively deliver anti-cancer agents to tumors, prolonging their presence, inducing immune responses, and rendering previously unresponsive tumors susceptible to immunotherapy, while minimizing long-term tissue accumulation and improving biocompatibility.
Implementation Method 1
the polymer and linker degradation products are small molecules that can be cleared by renal filtration
Implementation Method 2
High molecular weight polymer conjugates tend to circulate for long periods of time and accumulate efficiently in tumor tissue due to the enhanced permeability and retention (EPR) effect
Implementation Method 3
PD-L1 binds to a receptor, programmed cell death protein 1 (PD-1) that is found on activated T cells
Data Source
AI summary
Described herein are biodegradable drug delivery conjugates and anti-cancer conjugates for effectively delivering anti-cancer agents to a subject. The conjugates include a single first cleavable peptide linker covalently connected to two polymeric segments, wherein at least one PD-L1 inhibitor is covalently bonded to each polymeric segment (referred to herein as “a PD-L1 inhibitor polymer conjugate”). Also described herein is the use of the PD-L1 inhibitor polymer conjugates in combination with anticancer agents to treat or prevent cancer.