A Neutral Single-Molecule Carrier for Delivery of Phosphonate Drugs
Qingling Nie
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Juan Tang
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorYongsheng Li
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorJi Wang
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorProf. Dr. Boyang Li
School of Chemistry and Chemical Engineering College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100 China
Search for more papers by this authorProf. Dr. Hongwei Ma
Analysis & Testing Center, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorProf. Dr. Xiao-Juan Yang
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Wei Zhao
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Dr. Biao Wu
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorQingling Nie
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Juan Tang
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorYongsheng Li
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorJi Wang
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorProf. Dr. Boyang Li
School of Chemistry and Chemical Engineering College of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100 China
Search for more papers by this authorProf. Dr. Hongwei Ma
Analysis & Testing Center, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorProf. Dr. Xiao-Juan Yang
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Wei Zhao
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Prof. Dr. Biao Wu
Key Laboratory of Medicinal Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 102488 China
E-mail: [email protected]; [email protected]; [email protected]
Search for more papers by this authorGraphical Abstract
The first application of a neutral anion receptor as a “single-molecule carrier” for targeted delivery of phosphonate drugs into living cells through anion coordination.
Abstract
Phosphate/phosphonate-based drugs (PDs), as multinegative, hydrophilic molecules, face the greatest difficulty in diffusion across biological membranes, leading to poor bioavailability. Conventional drug delivery strategies to overcome this issue, including utilizing small-molecule prodrugs or nanoparticle carriers, often suffer from case-specific modifications or uncertainties in drug loading. Inspired by the anion coordination chemistry of natural phosphate transporters and artificial anion receptors, here, we present the first use of a neutral anion receptor, i.e., bis(tripodal hexaurea) cage 1, as a “single-molecule carrier” for the delivery of PDs into living cells. Cage 1 features advantages of molecular-level encapsulation, enhanced intracellular accumulation, subcellular targeting, responsive drug release, and broad adaptability. It enhances PD accumulation in tumor cells both in vitro and in vivo, enhancing the cellular uptake of mono-, di-, and tri-phosphate/phosphonate substrates by up to 45-fold via a macropinocytosis-mediated endocytosis pathway. This work demonstrates the potential of neutral anion receptors to serve as single-molecule carriers and offers a promising solution for improving PDs bioavailability, advancing the development of antitumor phosphate/phosphonate-based drugs.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the Supporting Information of this article.
Supporting Information
| Filename | Description |
|---|---|
| anie202509002-sup-0001-SuppMatS1.pdf5.3 MB | Supporting Information S1 |
| anie202509002-sup-0002-SuppMatS2.zip4.5 MB | Supporting Information S2 |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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