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A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication

A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication

Published on: September 20, 2016

Bioactive Artificial Cells as Autonomous Metabolic Actuators Enable Bidirectional Communication with Tumor Cells.

Lifan Hu¹, Wenwu Peng^1,2, Jiyao Yu¹

¹Max Planck Institute for Polymer Research, Ackermannweg 10, Mainz 55128, Germany.

Journal of the American Chemical Society

|December 12, 2025

Summary

Engineered artificial cells (ACs) with dual enzymes selectively convert tumor lactate into toxic acetaldehyde. This synthetic metabolic biointerface reprograms tumor microenvironments, suppressing cancer cell viability.

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A Mimic of the Tumor Microenvironment: A Simple Method for Generating Enriched Cell Populations and Investigating Intercellular Communication

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Tissue Engineering of a Human 3D in vitro Tumor Test System

Tissue Engineering of a Human 3D in vitro Tumor Test System

Published on: August 6, 2013

Area of Science:

Synthetic biology
Biotechnology
Cancer research

Background:

Artificial cells (ACs) offer a platform for metabolic reprogramming but struggle with autonomous metabolite exchange and tissue integration.
Glycolytic tumors accumulate lactate, a byproduct linked to immunosuppression and metastasis.
Lactate degradation can produce pyruvate, potentially fueling tumor growth.

Purpose of the Study:

To develop proteinosome-based ACs for bidirectional communication with glycolytic tumor cells.
To engineer ACs that selectively metabolize lactate without promoting tumor growth.
To establish synthetic metabolic biointerfaces as programmable actuators in cancer tissues.

Main Methods:

Coencapsulation of lactate oxidase (LOx) and pyruvate decarboxylase (PDC) into proteinosome-based ACs.
Engineering dual-processor ACs to convert lactate to acetaldehyde and suppress pyruvate accumulation.
Integration of ACs into 3D tumor spheroids to assess functionality and metabolite exchange.

Main Results:

ACs demonstrated sustained catalytic activity and maintained reactive oxygen species homeostasis.
Engineered ACs achieved autonomous, bidirectional metabolite exchange, preferentially with cancer cells.
The ACs dynamically altered tumor microenvironment metabolites and suppressed cancer cell viability.

Conclusions:

Dual-processor ACs effectively convert lactate into cytotoxic acetaldehyde, mitigating tumor-promoting byproducts.
Synthetic metabolic biointerfaces can be programmed to reshape pathological signaling in cancer.
This approach offers a novel strategy for cancer therapy by targeting tumor metabolism.