A Selective-Tumor-Penetrating Strategy via Unidirectional Direct Transfer for Intravesical Therapy of Bladder Cancer
A selective tumor-penetrating strategy generally exploits tumor-targeted ligands to modify drugs so that the conjugate preferentially enters tumors and subsequently undergoes transcellular transport to penetrate tumors. However, this process shields ligands from their corresponding targets on the cell surface, possibly inducing an off-target effect during drug penetration at the tumor-normal interface. Herein, we first describe a selective tumor-penetrating drug (R11-phalloidin conjugates) for intravesical therapy of bladder cancer. The intravesical conjugates rapidly translocated across the mucus layer, specifically bound to tumors, and infiltrated throughout the tumor via direct intercellular transfer. Notably, direct transfer from normal cells to tumor cells was unidirectional because the pathways required for direct transfer, termed F-actin-rich tunneling nanotubes, were more unidirectionally extended from normal cells to tumor cells. Moreover, the intravesical conjugates displayed strong anticancer activity and well-tolerated biosafety in murine orthotopic bladder tumor models. Our study demonstrated the potential of a selective tumor-penetrating conjugate for effective intravesical anticancer therapy.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
|---|---|
| Enthalten in: |
Journal of medicinal chemistry - 67(2024), 6 vom: 28. März, Seite 4904-4915 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Qin, Xiaowen [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Completed 29.03.2024 Date Revised 29.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1021/acs.jmedchem.4c00060 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369886542 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369886542 | ||
| 003 | DE-627 | ||
| 005 | 20240330001330.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240319s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1021/acs.jmedchem.4c00060 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1355.xml |
| 035 | |a (DE-627)NLM369886542 | ||
| 035 | |a (NLM)38499004 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Qin, Xiaowen |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A Selective-Tumor-Penetrating Strategy via Unidirectional Direct Transfer for Intravesical Therapy of Bladder Cancer |
| 264 | 1 | |c 2024 | |
| 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 29.03.2024 | ||
| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A selective tumor-penetrating strategy generally exploits tumor-targeted ligands to modify drugs so that the conjugate preferentially enters tumors and subsequently undergoes transcellular transport to penetrate tumors. However, this process shields ligands from their corresponding targets on the cell surface, possibly inducing an off-target effect during drug penetration at the tumor-normal interface. Herein, we first describe a selective tumor-penetrating drug (R11-phalloidin conjugates) for intravesical therapy of bladder cancer. The intravesical conjugates rapidly translocated across the mucus layer, specifically bound to tumors, and infiltrated throughout the tumor via direct intercellular transfer. Notably, direct transfer from normal cells to tumor cells was unidirectional because the pathways required for direct transfer, termed F-actin-rich tunneling nanotubes, were more unidirectionally extended from normal cells to tumor cells. Moreover, the intravesical conjugates displayed strong anticancer activity and well-tolerated biosafety in murine orthotopic bladder tumor models. Our study demonstrated the potential of a selective tumor-penetrating conjugate for effective intravesical anticancer therapy | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Wang, Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Wentao |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Haibao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhenghong |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Mou, Yixuan |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Cenchao |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yiyang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chenkai |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xuanyi |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Youqing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Pu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dahong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of medicinal chemistry |d 1963 |g 67(2024), 6 vom: 28. März, Seite 4904-4915 |w (DE-627)NLM000006602 |x 1520-4804 |7 nnns |
| 773 | 1 | 8 | |g volume:67 |g year:2024 |g number:6 |g day:28 |g month:03 |g pages:4904-4915 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1021/acs.jmedchem.4c00060 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 67 |j 2024 |e 6 |b 28 |c 03 |h 4904-4915 | ||