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A commensal bacterial platform for intracellular drug delivery in TNBC

Cancer is a global health challenge, affecting people in every corner of the world.

Global Burden of Breast Cancer

Cancer is a major global health challenge, and Breast Cancer—the most prevalent malignancy in women—presents complex biology and remains a central focus of research and treatment.

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Women
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Estimated Woman Lifetime Breast Cancer Risk
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Est. 2050 Breast Cancer Cases
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Est. 2050 Breast Cancer Death
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Advanced Stage Triple-Negative Breast Cancer (TNBC) Mortality Rate
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Clinical Challenges of Triple-Negative Breast Cancer (TNBC)

Triple-negative breast cancer lacks Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2), leaving no benefit from hormone or HER2-targeted therapies, and is often diagnosed late with poor prognosis.

Inspiration: Intracellular Microbiota in Triple-Negative Breast Cancer

Recent studies have shown that triple-negative breast cancer cells contain a certain number of bacteria, with the genus Staphylococcus exhibiting the highest relative abundance.

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Project Framework

We plan to develop a symbiotic bacterial platform capable of delivering drugs into triple-negative breast cancer cells, with the aim of providing new therapeutic options for patients in the future.

D1 Diagram

Staphylococcus species distribution in breast tumors

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Engineering Strategy: Enhanced Bacterial Invasion

We engineered Staphylococcus xylosus and Staphylococcus epidermidis to express the invasion protein FnBP, FnBPs bind to Fn, inducing a conformational change that exposes integrin-binding sites. Fn then interacts with \(α_{5}\)\(β_{1}\) integrin, which activates downstream signaling pathways, drives cytoskeletal rearrangement, and promotes bacterial invasion.

FnBPs bind to FnI, inducing exposure of integrin-binding sites on Fn
Bacterial Adhesion Step1
The Fn–FnBP complex engages α5β1 integrin, triggering bacterial internalization by the host cell
Bacterial Adhesion Step2
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TroGen achieved >99% TNBC cell invasion rate within 6 hours, with significant selectivity.
0%+ TroGen revealed an unprecedented invasiveness of a commensal strain, invading >50% TNBC cells with significant selectivity.

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