EGFR Targeted Redox Sensitive Chitosan Nanoparticles of Cabazitaxel : Dual-Targeted Cancer Therapy, Lung Distribution, and Targeting Studies by Photoacoustic and Optical Imaging
In this research, we have modified tocopheryl polyethylene glycol succinate (TPGS) to a redox-sensitive material, denoted as TPGS-SH, and employed the same to develop dual-receptor-targeted nanoparticles of chitosan loaded with cabazitaxel (CZT). The physicochemical properties and morphological characteristics of all nanoparticle formulations were assessed. Dual-receptor targeting redox-sensitive nanoparticles of CZT (F-CTX-CZT-CS-SH-NPs) were developed by a combination of pre- and postconjugation techniques by incorporating synthesized chitosan-folate (F) and TPGS-SH during nanoparticle synthesis and further postconjugated with cetuximab (CTX) for epidermal growth factor receptor (EGFR) targeting. The in vitro release of the drug was seemingly higher in the redox-sensitive buffer media (GSH, 20 mM) compared to that in physiological buffer. However, the extent of cellular uptake of dual-targeted nanoparticles was significantly higher in A549 cells than other control nanoparticles. The IC50 values of F-CTX-CZT-CS-SH-NPs against A549 cells was 0.26 ± 0.12 μg/mL, indicating a 6.3-fold and 60-fold enhancement in cytotoxicity relative to that of dual-receptor targeted, nonredox sensitive nanoparticles and CZT clinical injection, respectively. Furthermore, F-CTX-CZT-CS-SH-NPs demonstrated improved anticancer activity in the benzo(a)pyrene lung cancer model with a higher survival rate. Due to the synergistic combination of enhanced permeability and retention (EPR) effect of small-sized nanoparticles, the innovative and redox sensitive TPGS-SH moiety and the dual folate and EGFR mediated augmented endocytosis have all together significantly enhanced their biodistribution and targeting exclusively to the lung which is evident from their ultrasound/photoacoustic and in vivo imaging system (IVIS) studies.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
|---|---|
| Enthalten in: |
Biomacromolecules - 24(2023), 11 vom: 13. Nov., Seite 4989-5003 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Vikas [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
3WJQ0SDW1A |
|---|
| Anmerkungen: |
Date Completed 28.11.2023 Date Revised 28.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1021/acs.biomac.3c00658 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM363635521 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM363635521 | ||
| 003 | DE-627 | ||
| 005 | 20231226093755.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1021/acs.biomac.3c00658 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1212.xml |
| 035 | |a (DE-627)NLM363635521 | ||
| 035 | |a (NLM)37871263 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Vikas |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a EGFR Targeted Redox Sensitive Chitosan Nanoparticles of Cabazitaxel |b Dual-Targeted Cancer Therapy, Lung Distribution, and Targeting Studies by Photoacoustic and Optical Imaging |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 28.11.2023 | ||
| 500 | |a Date Revised 28.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a In this research, we have modified tocopheryl polyethylene glycol succinate (TPGS) to a redox-sensitive material, denoted as TPGS-SH, and employed the same to develop dual-receptor-targeted nanoparticles of chitosan loaded with cabazitaxel (CZT). The physicochemical properties and morphological characteristics of all nanoparticle formulations were assessed. Dual-receptor targeting redox-sensitive nanoparticles of CZT (F-CTX-CZT-CS-SH-NPs) were developed by a combination of pre- and postconjugation techniques by incorporating synthesized chitosan-folate (F) and TPGS-SH during nanoparticle synthesis and further postconjugated with cetuximab (CTX) for epidermal growth factor receptor (EGFR) targeting. The in vitro release of the drug was seemingly higher in the redox-sensitive buffer media (GSH, 20 mM) compared to that in physiological buffer. However, the extent of cellular uptake of dual-targeted nanoparticles was significantly higher in A549 cells than other control nanoparticles. The IC50 values of F-CTX-CZT-CS-SH-NPs against A549 cells was 0.26 ± 0.12 μg/mL, indicating a 6.3-fold and 60-fold enhancement in cytotoxicity relative to that of dual-receptor targeted, nonredox sensitive nanoparticles and CZT clinical injection, respectively. Furthermore, F-CTX-CZT-CS-SH-NPs demonstrated improved anticancer activity in the benzo(a)pyrene lung cancer model with a higher survival rate. Due to the synergistic combination of enhanced permeability and retention (EPR) effect of small-sized nanoparticles, the innovative and redox sensitive TPGS-SH moiety and the dual folate and EGFR mediated augmented endocytosis have all together significantly enhanced their biodistribution and targeting exclusively to the lung which is evident from their ultrasound/photoacoustic and in vivo imaging system (IVIS) studies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a alpha-Tocopherol |2 NLM | |
| 650 | 7 | |a H4N855PNZ1 |2 NLM | |
| 650 | 7 | |a cabazitaxel |2 NLM | |
| 650 | 7 | |a 51F690397J |2 NLM | |
| 650 | 7 | |a Chitosan |2 NLM | |
| 650 | 7 | |a 9012-76-4 |2 NLM | |
| 650 | 7 | |a EGFR protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a ErbB Receptors |2 NLM | |
| 650 | 7 | |a EC 2.7.10.1 |2 NLM | |
| 650 | 7 | |a Folic Acid |2 NLM | |
| 650 | 7 | |a 935E97BOY8 |2 NLM | |
| 650 | 7 | |a Polyethylene Glycols |2 NLM | |
| 650 | 7 | |a 3WJQ0SDW1A |2 NLM | |
| 650 | 7 | |a Taxoids |2 NLM | |
| 700 | 1 | |a Mehata, Abhishesh Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Viswanadh, Matte Kasi |e verfasserin |4 aut | |
| 700 | 1 | |a Malik, Ankit Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Setia, Aseem |e verfasserin |4 aut | |
| 700 | 1 | |a Kumari, Pooja |e verfasserin |4 aut | |
| 700 | 1 | |a Mahto, Sanjeev Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Muthu, Madaswamy S |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biomacromolecules |d 2000 |g 24(2023), 11 vom: 13. Nov., Seite 4989-5003 |w (DE-627)NLM116020989 |x 1526-4602 |7 nnns |
| 773 | 1 | 8 | |g volume:24 |g year:2023 |g number:11 |g day:13 |g month:11 |g pages:4989-5003 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1021/acs.biomac.3c00658 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 24 |j 2023 |e 11 |b 13 |c 11 |h 4989-5003 | ||