Drug-Free Approach to Regulate Undruggable Proto-Oncogene MYC Using Biomimetic Porous Nanoparticles for Cancer Immunotherapy
A proto-oncogene MYC plays a crucial role in controlling immune response, but as of today, it is undruggable. Some MYC inhibitors are under testing; nevertheless, they have low efficacy and severe toxicity. Up to now, the use of a drug-free approach to regulate MYC has been rarely investigated. The present study aims to identify the potential of drug-free photothermal therapy (PTT) in regulating MYC. Herein, biomimetic black porous silicon (BPSi) nanoparticles (NPs) were prepared via a novel self-templated Na-K alloy reduction method and then coated with a cancer cell membrane and polyethylene glycol. These NPs have efficient photothermal conversion, good biocompatibility, and homotypic tumor targeting. The results indicated that BPSi-based PTT could efficiently regulate MYC by tuning temperatures. However, only PTT at 50 °C could successfully inhibit MYC, while PTT at 46 °C upregulated MYC. Mechanism studies revealed that MYC inhibition was achieved via the downregulation of 'MYC Targets V1', and MAPK and JAK-STAT signaling pathways were involved. Finally, tumor-targeted PTT activated robust cancer immunotherapy by MYC inhibition and efficiently prevented tumor growth without significant toxicity in vivo. The present study highlights the potential of a drug-free approach to regulate MYC for more potent cancer immunotherapy.
Authors
- Minna Unelma Kaikkonen (ORCID: https://orcid.org/0000-0001-6294-0979)
- Mari Taipale (ORCID: https://orcid.org/0000-0001-6805-4599)
- Haijun Yu (ORCID: https://orcid.org/0000-0002-3398-0880)
- Minna Sivonen
- Wujun Xu (ORCID: https://orcid.org/0000-0002-3177-4709)
- Vesa‐Pekka Lehto (ORCID: https://orcid.org/0000-0001-8153-1070)
- Henri Leinonen (ORCID: https://orcid.org/0000-0002-0388-832X)
- Tiit Örd (ORCID: https://orcid.org/0000-0002-3098-1749)
- Henri Hakkarainen (ORCID: https://orcid.org/0000-0002-8461-4565)
- Konstantin Tamarov (ORCID: https://orcid.org/0000-0003-0087-4878)
- Emilia Happonen (ORCID: https://orcid.org/0000-0002-1271-2457)
- Ahmed B. Montaser (ORCID: https://orcid.org/0000-0003-4511-467X)
- Juha Klefström (ORCID: https://orcid.org/0000-0001-7124-8431)
- Jenni Küblbeck (ORCID: https://orcid.org/0000-0002-6439-4403)
- Ruixian Liu (ORCID: https://orcid.org/0000-0002-3065-6743)
- Yijing Dang (ORCID: https://orcid.org/0000-0001-5580-3888)
- Jiajia Wang (ORCID: https://orcid.org/0000-0002-0897-8033)
- Zhiai Xu (ORCID: https://orcid.org/0000-0002-4391-2507)
- Silja Saarela
- Milla-Iida Laari
- Mohammed Zakir
- Yiannis Constantinou
Institutions
- University of Helsinki (FI)
- University of Eastern Finland (FI)
- University of California, San Francisco (US)
- Chinese Academy of Sciences (CN)
- National Medical Products Administration (CN)
- Helsinki University Hospital (FI)
- University of California System (US)
- Finnish Cancer Registry (FI)
- Finland University (FI)
- Translational Research in Oncology (FR)
- Shanghai Institute of Materia Medica (CN)
- Institute for Molecular Science (JP)
- Cancer Society of Finland (FI)
- East China Normal University (CN)
Publication Details
- Journal
- ACS Applied Materials & Interfaces
- Published
- 2025-08-11
- DOI
- https://doi.org/10.1021/acsami.5c05042
- Citations
- 1
- Primary Topic
- Nanoplatforms for cancer theranostics
- Type
- article
- Field-Weighted Citation Impact
- 0.67
Funders
- National Natural Science Foundation of China
- Academy of Finland
- Suomen Kulttuurirahasto
- Syöpäsäätiö