# Autonomous metal-organic framework nanorobots for active mitochondria-targeted cancer therapy

**Authors:** Xiqi Peng, Songsong Tang, Daitian Tang, Dewang Zhou, Yangyang Li, Qiwei Chen, Fangchen Wan, Heather Lukas, Hong Han, Xueji Zhang, Wei Gao, Song Wu

PMC · DOI: 10.1126/sciadv.adh1736 · 2023-06-09

## TL;DR

Researchers developed autonomous nanorobots that deliver drugs directly to mitochondria in cancer cells, improving treatment effectiveness and reducing side effects.

## Contribution

The nanorobots use a metal-organic framework to enable active, mitochondria-targeted drug delivery within tumor cells.

## Key findings

- The nanorobots induce mitochondria-mediated apoptosis and dysregulation in cancer cells.
- They show improved in vitro anticancer effects and suppression of cancer cell metastasis.
- In vivo tests confirmed their efficacy in subcutaneous and orthotopic breast tumor models.

## Abstract

Nanorobotic manipulation to access subcellular organelles remains unmet due to the challenge in achieving intracellular controlled propulsion. Intracellular organelles, such as mitochondria, are an emerging therapeutic target with selective targeting and curative efficacy. We report an autonomous nanorobot capable of active mitochondria-targeted drug delivery, prepared by facilely encapsulating mitochondriotropic doxorubicin-triphenylphosphonium (DOX-TPP) inside zeolitic imidazolate framework-67 (ZIF-67) nanoparticles. The catalytic ZIF-67 body can decompose bioavailable hydrogen peroxide overexpressed inside tumor cells to generate effective intracellular mitochondriotropic movement in the presence of TPP cation. This nanorobot-enhanced targeted drug delivery induces mitochondria-mediated apoptosis and mitochondrial dysregulation to improve the in vitro anticancer effect and suppression of cancer cell metastasis, further verified by in vivo evaluations in the subcutaneous tumor model and orthotopic breast tumor model. This nanorobot unlocks a fresh field of nanorobot operation with intracellular organelle access, thereby introducing the next generation of robotic medical devices with organelle-level resolution for precision therapy.

Autonomous MOF-based nanorobots enable active and targeted drug delivery to intracellular organelles for cancer therapy.

## Linked entities

- **Chemicals:** doxorubicin (PubChem CID 31703), hydrogen peroxide (PubChem CID 784)
- **Diseases:** cancer (MONDO:0004992), breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, HLA-DRA (major histocompatibility complex, class II, DR alpha) [NCBI Gene 3122] {aka HLA-DRA1}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, DNTT (DNA nucleotidylexotransferase) [NCBI Gene 1791] {aka TDT}, Dntt (deoxynucleotidyltransferase, terminal) [NCBI Gene 21673] {aka Tdt}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, Casp9 (caspase 9) [NCBI Gene 12371] {aka APAF-3, CASP-9, Caspase-9, ICE-LAP6, Mch6}, CAT (catalase) [NCBI Gene 847]
- **Diseases:** Cancer (MESH:D009369), Mitochondrial dysfunction (MESH:D028361), necrosis (MESH:D009336), breast cancer (MESH:D001943), metastatic (MESH:D000092182), weight loss (MESH:D015431), inflammation (MESH:D007249), atherosclerosis (MESH:D050197), liver (MESH:D017093), bladder cancer (MESH:D001749), liver metastases (MESH:D009362), Cytotoxicity (MESH:D064420), neurodegeneration (MESH:D019636), pathological disorders (MESH:D005598), mitochondrial dysregulation (MESH:D021081)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Mutations:** F200X
- **Cell lines:** BIU-87/ADR — Unidentified organism (Unknown organism), Undefined cell line type (CVCL_6881), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), 4T1 breast cancer — Homo sapiens (Human), Transformed cell line (CVCL_WC49), ZIF-67 — Mus musculus (Mouse), Hybridoma (CVCL_B7D2), BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), 4T1 breast tumor — Homo sapiens (Human), Breast carcinoma, Cancer cell line (CVCL_5G43), T24 bladder tumor — Mus musculus (Mouse), Mouse bladder transitional cell carcinoma, Cancer cell line (CVCL_4660), 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), T24 — Homo sapiens (Human), Bladder carcinoma, Cancer cell line (CVCL_0554), T24 bladder cancer — Homo sapiens (Human), Bladder carcinoma, Cancer cell line (CVCL_VL60), SV- HUC-1 — Homo sapiens (Human), Transformed cell line (CVCL_3798), UIO-66 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_9722)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC10256165/full.md

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Source: https://tomesphere.com/paper/PMC10256165