Folic Acid and Poly(ethylene glycol) Decorated Paclitaxel Nanocrystals Exhibit Enhanced Stability and Breast Cancer-Targeting Capability
Abstract
In part because of their high drug loading, nanocrystals (NCs) have seen extensive use in drug delivery, particularly for insoluble or poorly soluble drugs. It remains a challenge, however, to prepare stable nanocrystals with tumor-targeting capability. Here, we designed a novel preparation of stable paclitaxel (PTX) nanocrystals with efficient active tumor-targeting properties. PTX NC was prepared using a bottom-up method and modified with both poly(ethylene glycol) (PEG) and folic acid (FA) derivatives using film hydration. The resulting PTX NC@lipid–PEG–FA had a rodlike shape, with hydrodynamic diameters and drug loading values of 201.90 ± 2.92 nm and 31.07 ± 3.41%, respectively. The size of the PTX NC@lipid–PEG–FA was unchanged after 168 h in the presence of plasma, whereas nonmodified paclitaxel nanocrystals (PTX NC) exceeded 600 nm within 12 h under the same conditions. Cellular uptake and cellular growth inhibition experiments in 4T1 breast cancer cells showed the superiority of PTX NC@lipid–PEG–FA over PTX NC or PEGylated paclitaxel nanocrystals without FA modification (PTX NC@lipid–PEG). A pharmacokinetic evaluation in rats revealed that PTX NC@lipid–PEG–FA significantly prolonged the circulation of PTX in the bloodstream, in comparison with PTX NC or Taxol. Tissue distribution and in vivo antitumor studies in 4T1 orthotopic breast cancer-bearing nude mice showed that PTX NC@lipid–PEG–FA significantly increased the intratumor accumulation of PTX and efficiently inhibited tumor growth, in comparison with PTX NC@lipid–PEG, PTX NC, or Taxol. In summary, PTX NC@lipid–PEG–FA showed good potential for breast cancer-targeted delivery for insoluble therapeutics.
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Folate receptor is overexpressed on the surface of a variety of cancers including breast, kidney, colorectal, brain, and ovarian cancers.
“The folate receptor (FR) is overexpressed on the surface of a variety of cancers, including breast, kidney, colorectal, brain, and ovarian cancers.263–265”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [265]
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- Authors
- Zhao, J., Du, J., Wang, J., An, N., Zhou, K., Hu, X., Dong, Z., & Liu, Y.
- Affiliations
- Shanghai University of Traditional Chinese Medicine (CN)
- Fudan University (CN)
- Corresponding author
- Dong, Zhiying
- Liu, Yu
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2021-03-17
- Volume
- 13
- Issue
- 12
- Pages
- 14577-14586
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W3137867853
- Cited by
- 69
- References
- 28
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 9 · 2023: 15 · 2022: 12 · 2021: 2
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81573361)
- State Key Laboratory for Advanced Pharmaceutical Formulation with High Technology
- Shanghai Nature Science Foundation (18ZR1439600)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- folic acid, polyethylene glycol, anticancer drug delivery, breast cancer, nanocrystal stability, film hydration, PEGylation, lipids, 4T1 cells, pharmacokinetics, poorly water-soluble drugs
- MeSH terms
- Animals, Antineoplastic Agents, Phytogenic, Breast Neoplasms, Drug Carriers, Female, Folic Acid, Humans, Mice, Nude, Polyethylene Glycols, Drug Delivery Systems, Paclitaxel, Mice, Rats, Nanoparticles
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