Engineered Adipocytes for Targeted Anti-Cancer Prodrug Delivery
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current cancer therapies face challenges in effectively targeting the adipocyte microenvironment, which supports tumor growth by providing energy to cancer cells through lipolysis, and in achieving sustained release of anti-cancer therapeutics within the tumor tissue.
Innovation Solution
Engineered adipocytes are developed to encapsulate anti-cancer prodrugs, such as doxorubicin prodrug, conjugated with fatty acids like rumenic acid, using environmentally responsive linkers, and equipped with fatty-acid binding protein 4 (FABP4) for targeted delivery and sustained release within the tumor microenvironment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer therapies are used, then anti-cancer agents can be delivered to tumor tissue, but the therapies cannot effectively target the adipocyte microenvironment or achieve sustained release within the tumor
Solution Approach 1:
The engineered adipocytes utilize the tumor microenvironment's own lipolytic activity and fatty acid metabolism pathways to trigger therapeutic release. The system self-activates through endogenous enzymes and metabolic processes, eliminating the need for external triggers or complex control mechanisms while achieving targeted delivery to the adipocyte microenvironment
Solution Approach 2:
The patent employs environmentally responsive linkers that change their chemical state in response to specific parameters in the tumor microenvironment, such as pH changes, enzymatic activity, or redox conditions. This allows the delivery system to remain stable during circulation but automatically activate and release the therapeutic payload when encountering the unique biochemical parameters of the tumor adipocyte microenvironment
2Reliability
If anti-cancer agents are delivered systemically, then broad coverage is achieved, but side effects increase and sustained release at the tumor site is not achieved
Solution Approach 1:
The engineered adipocytes act as intermediary carriers that transport the therapeutic payload from the bloodstream to the tumor adipocyte microenvironment. These living cells serve as a bridge between systemic administration and localized delivery, protecting the therapeutic during circulation and releasing it only at the target site through interactions with tumor-associated macrophages and lipolytic enzymes
Solution Approach 2:
The patent extracts and utilizes specific components of the tumor microenvironment, such as lipolytic enzymes and fatty acid metabolism pathways, to trigger therapeutic release. By harnessing these endogenous tumor-specific processes, the system achieves localized sustained release without requiring systemic administration, thereby minimizing exposure of healthy tissues to 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 engineered adipocytes effectively inhibit cancer cell growth, suppress tumor-promoting adipokines, and enhance immune cell infiltration, leading to significant tumor growth inhibition and reduced recurrence, while minimizing side effects through targeted and sustained delivery of anti-cancer agents.
Implementation Method 1
the prodrug can be conjugated to the conjugated fatty acid via an environmentally reactive linker (such as, for example, a pH sensitive, enzymatic, and/or reactive oxygen species responsive linker)
Implementation Method 2
the prodrug can be conjugated to the conjugated fatty acid via an environmentally reactive linker (such as, for example, a pH sensitive, enzymatic, and/or reactive oxygen species responsive linker)
Implementation Method 3
adipocytes further comprising a lipid transport protein (such as, for example) fatty-acid binding protein 4 (FABP4)
Data Source
Figure 1A~1K
Figure 2A~2L
Figure 3A~3F
AI summary
Disclosed are compositions and methods related to the use of adipocytes for sustained release of anti-cancer therapeutics and treatment of cancer.