Theranostic size-reducible and no donor conjugated gold nanocluster fabricated hyaluronic acid nanoparticle with optimal size for combinational treatment of breast cancer and lung metastasis
Abstract
The size of nanoparticles plays a key role in utilizing enhanced permeability and retention (EPR) effect of tumor, where large-sized nanoparticles possess good retention but poor penetration, while small-sized nanoparticles are on the contrary. Although size-reducible nanoparticles have been designed to partially overcome this dilemma, the initial size and complicated tumor microenvironment remain restricting the tumor distribution of nanoparticles. Herein, we employed tumor-specific CD44 targeted, hyaluronidase-degradable hyaluronic acid (HA) and small-sized, renal-clearable, red emission, cationic bovine serum albumin-protected gold nanocluster (AuNC@CBSA) to successfully construct size-reducible nanoplatform (AuNC@CBSA@HA). By changing the ratio of HA and AuNC@CBSA, different initial sizes of AuNC@CBSA@HA were prepared and their tumor targeting efficiencies, pharmacokinetic profiles were evaluated. Then 200 nm of AuNC@CBSA@HA with optimal EPR effect was screened out to further load paclitaxel (PTX) and indocyanine green (ICG) for chemo- photothermal therapy and nitric oxide (NO) for modulating tumor microenvironment and enhancing drug delivery. The AuNC@CBSA-PTX-ICG@HA-NO 3 showed size-reducible ability under triggering by hyaluronidase and high accumulation in breast cancer with homogenous intra-tumor distribution, suppressed 95.3% of in-situ tumor growth and inhibited 88.4% of lung metastasis growth. In conclusion, we provide a strategy that fully satisfied the concerns in drug delivery to tumor for improved antitumor effect.
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HA-based nanodrugs could be assembled more at the tumor by EPR effect through binding to CD44.
“HA (hyaluronic acid)-based nanodrugs could be assembled more at the tumor by EPR effect through binding to CD44 [52].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [52]
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- Authors
- Liu, R., Xiao, W., Hu, C., Xie, R., & Gao, H.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- Gao, Huile
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 278
- Pages
- 127-139
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2796274297
- Cited by
- 250
- References
- 43
- Citations by year
- 2026: 11 · 2025: 23 · 2024: 22 · 2023: 26 · 2022: 36 · 2021: 32 · 2020: 36 · 2019: 45 · 2018: 19
- FWCI
- 13.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31571016)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Materials Science › Materials Chemistry › Nanocluster Synthesis and Applications
- Keywords
- gold nanoclusters, hyaluronic acid nanoparticles, enhanced permeability and retention effect, CD44 targeting, renal clearance, paclitaxel, indocyanine green, chemo-photothermal therapy, nitric oxide, tumor microenvironment modulation, breast cancer, lung metastasis, theranostics, nanoparticle size optimization
- MeSH terms
- Theranostic Nanomedicine, Animals, Antineoplastic Agents, Phytogenic, Breast Neoplasms, Female, Gold, Hyaluronic Acid, Indocyanine Green, Lung Neoplasms, Mice, Inbred BALB C, Mice, Nude, Nitric Oxide, Particle Size, Serum Albumin, Bovine, Drug Delivery Systems, Paclitaxel, Hyaluronan Receptors, Nitric Oxide Donors, Mice, Nanoparticles, Tumor Microenvironment
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