Copper sulfide nanoparticle-based localized drug delivery system as an effective cancer synergistic treatment and theranostic platform
Abstract
Localized cancer treatment with combination therapy has attracted increasing attention for effective inhibition of tumor growth. In this work, we introduced diffusion molecular retention (DMR) tumor targeting effect, a new strategy that employed transferrin (Tf) modified hollow mesoporous CuS nanoparticles (HMCuS NPs) to undergo extensive diffuse through the interstitium and tumor retention after a peritumoral (PT) injection. Herein, HMCuS NPs with strong near-infrared (NIR) absorption and photothermal conversion efficiency could serve as not only a drug carrier but also a powerful contrast agent for photoacoustic imaging to guide chemo-phototherapy. The iron-dependent artesunate (AS), which possessed profound cytotoxicity against tumor cell, was used as model drug. As a result, this AS loaded Tf-HMCuS NPs (AS/Tf-HMCuS NPs) system could specially target to tumor cells and synchronously deliver AS as well as irons into tumor to achieve enhanced antitumor activity. It was found that AS/Tf-HMCuS NPs was taken up by MCF-7 cells via Tf-mediated endocytosis, and could effectively convert NIR light into heat for photothermal therapy as well as generated high levels of reactive oxygen species (ROS) for photodynamic therapy. In addition, in vivo antitumor efficacy studies showed that tumor-bearing mice treated with AS/Tf-HMCuS NPs through peritumoral (PT) injection under NIR laser irradiation displayed the strongest inhibition rate of about 74.8%, even with the reduced frequency of administration. Furthermore, to demonstrate DMR, the optical imaging, photoacoustic tomography and immunofluorescence after PT injection were adopted to track the behavior of AS/Tf-HMCuS NPs in vivo. The results exhibited that Tf-HMCuS NPs prolonged the local accumulation and retention together with slow vascular uptake and extensive interstitial diffusion, which was consistent with the biodistribution studies of AS/Tf-HMCuS NPs. Therefore, the approach of localized delivery through DMR combined with multi-mechanism therapy may be a promising method for cancer treatment.Statement of significance In recent years, localized cancer treatment using different biomaterials has attracted increasing attention for effective inhibition of tumor growth. However, it is still challenging for this kind of system to achieve a high drug loading, overcome biological barriers from the site of injection to the site of action, and combine synergetic therapy with diagnosis without adversely affecting the formation process. This study provides a localized diffusion molecular retention (DMR) tumor targeting drug delivery system based on hollow mesoporous copper sulfide nanoparticles (HMCuS NPs) entrapment of anticancer drug for the first time, which can achieve high drug loading, improve local drug accumulation and retention, accomplish synergistic combination of chemo-phototherapy, and finally enhance antitumor effect. In addition, HMCuS NPs also possesses the property suitable for photoacoustic imaging, which could offer us a theranostic platform.
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Tf-modified copper sulfide nanoparticles loaded with artesunate specifically target tumor cells, are absorbed by breast cancer cells via Tf-mediated endocytosis, deliver AS and iron, and enhance anti-tumor activity.
“Hou et al. anchored Tf on the surface of copper sulfide nanoparticles as a targeting molecule, loaded with artesunate. The system can specifically target tumor cells and be absorbed by breast cancer cells through tf-mediated endocytosis, while delivering As and iron ions to the tumor, thereby enhancing anti-tumor activity.271”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [271]
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- Authors
- Hou, L., Shan, X., Hao, L., Feng, Q., & Zhang, Z.
- Affiliations
- Zhengzhou University (CN)
- Corresponding author
- Zhang, Zhenzhong
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 54
- Pages
- 307-320
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W2594517351
- Cited by
- 128
- References
- 40
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 10 · 2023: 17 · 2022: 19 · 2021: 22 · 2020: 20 · 2019: 10 · 2018: 12 · 2017: 2
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81273451)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Keywords
- copper sulfide nanoparticles, transferrin targeting, peritumoral injection, photothermal therapy, photodynamic therapy, artesunate, reactive oxygen species, photoacoustic imaging, theranostics, chemo-phototherapy, tumor targeting, MCF-7 cells, combination cancer therapy, tissue distribution
- MeSH terms
- Theranostic Nanomedicine, Animals, Antineoplastic Agents, Contrast Media, Copper, Female, Humans, Neoplasms, Experimental, Sulfides, Drug Delivery Systems, Xenograft Model Antitumor Assays, Mice, Nanoparticles, MCF-7 Cells
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