pH-Triggered Dynamic Carrier-Free Nanodrugs Self-Assembled from Dasatinib and Chlorambucil with a Potential for Precise Tumoral Targeting Theranostic
Purpose Dynamic carrier-free theranostic nanodrugs are in great demand, owing to their extraordinary high drug loading, enhanced targeting therapy, and panoramic tracking of the drug behaviors. Herein, this work highlights a successful development of pH-triggered dynamic carrier-free nanodrugs for precise tumoral targeting theragnostic, which are established through self-assembly between dasatinib (DAS) and chlorambucil (CLB). Methods The study has proved the structure, change in particle size and zeta potential, fluorescence transition, cellular uptake, cytotoxicity as well as biosafety of the carrier-free nanodrugs. The nanodrugs are characterized by Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, X-ray diffraction, Dynamic light scattering, and Microplate reader. Cellular uptake and cytotoxicity assay are conducted for free drugs and their nanodrugs using tumor cell lines including A549, HepG2, K562, and THP1. ICR mice are applied to evaluate the biosafety of nanodrugs. Results The introduction of CLB into DAS nanoparticles can successfully redshift the emission wavelength from 420 to 810 nm. Moreover, the nanodrugs exhibit a dynamic fluorescence intensity conversion via tumoral intracellular gradual quenching of Aggregation-induced emission (AIE). This characteristic is beneficial to the precise monitoring of tumoral intracellular drug behaviors. Furthermore, the nanodrugs show a small-to-large size transition from 175 nm to more than 500 nm in 12 h and surficial charge reversal from −2.3 mV to more than 0.2 mV by protonation at tumoral pHs. These superior properties facilitate the improved cellular uptake and synergistic cytotoxicity on various types of tumor cells. Conclusion The study shows that nanodrugs made of DAS and CLB that can self-assemble without carriers under different pH levels may be ready for testing in tumor targeting, and might someday be helpful for diagnosis and treatment in the future..
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
|---|---|
| Enthalten in: |
Journal of pharmaceutical innovation - 18(2023), 4 vom: 30. Nov., Seite 2419-2428 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Yuanpeng [VerfasserIn] |
|---|
| Links: |
Volltext [lizenzpflichtig] |
|---|
| Themen: |
Aggregation-induced emission |
|---|
| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
|---|
| doi: |
10.1007/s12247-023-09801-x |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
SPR054308429 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | SPR054308429 | ||
| 003 | DE-627 | ||
| 005 | 20240109064654.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240109s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s12247-023-09801-x |2 doi | |
| 035 | |a (DE-627)SPR054308429 | ||
| 035 | |a (SPR)s12247-023-09801-x-e | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Yuanpeng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a pH-Triggered Dynamic Carrier-Free Nanodrugs Self-Assembled from Dasatinib and Chlorambucil with a Potential for Precise Tumoral Targeting Theranostic |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. | ||
| 520 | |a Purpose Dynamic carrier-free theranostic nanodrugs are in great demand, owing to their extraordinary high drug loading, enhanced targeting therapy, and panoramic tracking of the drug behaviors. Herein, this work highlights a successful development of pH-triggered dynamic carrier-free nanodrugs for precise tumoral targeting theragnostic, which are established through self-assembly between dasatinib (DAS) and chlorambucil (CLB). Methods The study has proved the structure, change in particle size and zeta potential, fluorescence transition, cellular uptake, cytotoxicity as well as biosafety of the carrier-free nanodrugs. The nanodrugs are characterized by Fourier transform infrared spectroscopy, 1H nuclear magnetic resonance, X-ray diffraction, Dynamic light scattering, and Microplate reader. Cellular uptake and cytotoxicity assay are conducted for free drugs and their nanodrugs using tumor cell lines including A549, HepG2, K562, and THP1. ICR mice are applied to evaluate the biosafety of nanodrugs. Results The introduction of CLB into DAS nanoparticles can successfully redshift the emission wavelength from 420 to 810 nm. Moreover, the nanodrugs exhibit a dynamic fluorescence intensity conversion via tumoral intracellular gradual quenching of Aggregation-induced emission (AIE). This characteristic is beneficial to the precise monitoring of tumoral intracellular drug behaviors. Furthermore, the nanodrugs show a small-to-large size transition from 175 nm to more than 500 nm in 12 h and surficial charge reversal from −2.3 mV to more than 0.2 mV by protonation at tumoral pHs. These superior properties facilitate the improved cellular uptake and synergistic cytotoxicity on various types of tumor cells. Conclusion The study shows that nanodrugs made of DAS and CLB that can self-assemble without carriers under different pH levels may be ready for testing in tumor targeting, and might someday be helpful for diagnosis and treatment in the future. | ||
| 650 | 4 | |a Aggregation-induced emission |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Carrier-free nanodrugs |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Dynamic changes |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Targeted theranostic |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Zhang, Chensong |4 aut | |
| 700 | 1 | |a Zhou, Shaobo |4 aut | |
| 700 | 1 | |a Chu, Liang |4 aut | |
| 700 | 1 | |a Fang, Wei |0 (orcid)0009-0007-0809-3044 |4 aut | |
| 700 | 1 | |a Ma, Jiachi |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of pharmaceutical innovation |d New York, NY : Springer, 2006 |g 18(2023), 4 vom: 30. Nov., Seite 2419-2428 |w (DE-627)SPR024593338 |w (DE-600)2428208-X |x 1939-8042 |7 nnns |
| 773 | 1 | 8 | |g volume:18 |g year:2023 |g number:4 |g day:30 |g month:11 |g pages:2419-2428 |
| 856 | 4 | 0 | |u https://dx.doi.org/10.1007/s12247-023-09801-x |z lizenzpflichtig |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_SPRINGER | ||
| 951 | |a AR | ||
| 952 | |d 18 |j 2023 |e 4 |b 30 |c 11 |h 2419-2428 | ||