A Protein Shield for Next-Generation Photothermal Nanomedicine

In a study Biomedical Analysis, researchers from Guizhou Medical University developed nanoparticles using a biomineralization-inspired strategy and demonstrated that the protein-coated system exhibits excellent colloidal stability, pH-responsive behavior, low biological toxicity, and effective near-infrared (NIR)-induced killing of breast cancer cells. Distinct from complex multi-step modification of traditional CuS nanomaterials, this one-pot 37 ℃ biomineralization route avoids toxic organic reagents, featuring simple operation, high repeatability and prominent industrial scalability.

Photothermal therapy (PTT) is an emerging cancer treatment strategy that uses near-infrared (NIR) light-responsive materials to generate heat and damage tumor cells. Copper sulfide (CuS) nanoparticles are promising photothermal agents due to their strong NIR absorption and efficient photothermal conversion, but their biomedical translation is limited by aggregation, insufficient physiological stability, and biocompatibility concerns.

To address these limitations, the research team introduced bovine serum albumin, a naturally occurring protein with excellent biocompatibility and stability, as a protective coating for CuS nanoparticles. The resulting CuS@BSA nanoparticles were synthesized through a biomineralization process, creating a stable nanostructure in which BSA acts as a natural protective shell, preventing nanoparticle aggregation while improving stability under biologically relevant conditions.

Building a Stable and Responsive Nanoplatform

The researchers scharacterized the physicochemical properties of CuS@BSA nanoparticles using dynamic light scattering, UV-visible spectroscopy and Fourier transform infrared spectroscopy. The nanoparticles displayed a uniform size distribution, with an average hydrated diameter of approximately 78 nm and a narrow polydispersity index, indicating good dispersion and structural uniformity.

Further experiments showed that CuS@BSA nanoparticles maintained stable properties during long-term storage, dilution, and incubation with serum conditions. The protein coating helped prevent nanoparticle aggregation, supporting their potential use in biological environments.

The nanoparticles also demonstrated pH-responsive aggregation behavior. Under acidic conditions similar to the intracellular environment of tumors, CuS@BSA nanoparticles showed increased aggregation due to changes in surface charge. This responsive feature may provide opportunities for designing environment-sensitive photothermal nanomaterials, although further studies are required to evaluate their behavior in vivo.

Turning Near-Infrared Light into Antitumor Activity

The researchers next evaluated the biological safety and antitumor efficacy of CuS@BSA nanoparticles on dual cell models: mouse breast cancer 4T1 cells and normal human umbilical vein endothelial (HUVEC) cells. Without laser irradiation, the nanoparticles kept cell viability above 90% for HUVEC and over 80% for 4T1 — even at the maximum test concentration, verifying extremely low dark toxicity and good biosafety to normal cells. This result indicates that the BSA coating improves the biocompatibility of the nanoplatform.

When exposed to an 808 nm near-infrared laser, however, CuS@BSA nanoparticles generated significant photothermal effects and effectively inhibited 4T1 cancer cell growth. Cell viability assays and live/dead staining experiments demonstrated that the combination of CuS@BSA nanoparticles and NIR irradiation resulted in substantial tumor cell death, while laser irradiation alone or nanoparticles without irradiation caused minimal damage.

These findings indicate that CuS@BSA nanoparticles can function as a light-activated therapeutic platform, remaining relatively safe under normal conditions while producing photothermal effects when externally triggered.

Toward Future Cancer Nanotherapies

This study provides a foundation for developing protein-stabilized copper sulfide nanomaterials for photothermal cancer therapy. By combining the photothermal properties of CuS nanoparticles with the biocompatibility and stabilization advantages of BSA, the developed nanoplatform addresses several limitations associated with conventional inorganic photothermal agents. The researchers acknowledged that further investigations, including animal studies, biodistribution analysis, and comprehensive safety evaluations, are needed to determine the future translational potential of CuS@BSA nanoparticles.

“Our goal was to combine the photothermal capability of copper sulfide nanoparticles with the biological advantages of albumin,” said Dr. Ying Chen, corresponding author of the study. “This design provides a promising platform for exploring safer and more effective nanomaterial-based cancer therapies.”

Contact the author:

Ying Chen, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine & School of Pharmaceutical Sciences, Guizhou Medical University, China, ychen1214@163.com. 

Funder: 

This work was supported by the National Natural Science Foundation of China (Nos. 82304404 and 32560230), the Guizhou Provincial Basic Research Program (Natural Science, Nos. ZK[2023]303 and MS[2025]564), and the Cultivation Project of National Natural Science Foundation of Guizhou Medical University (No. 24NSFCP05).

Conflict of interest: 

The authors declared that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

See the article: 

Shengli Shen, Preparation and Evaluation of Bovine Serum Albumin-Protected Copper Sulfide Nanoparticles, Biomedical Analysis, Volume 3, Issue 3,  2026, Pages 69-77. https://doi.org/10.1016/j.bioana.2026.07.001