Delivery of Cationic Platinum Prodrugs via Reduction Sensitive Polymer for Improved Chemotherapy.
Small
; 17(45): e2101804, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34554644
ABSTRACT
A cationic monofunctional platinum anticancer drug, phenanthriplatin (PhenPt(II)), exhibits promising anticancer effect on various cancer cell lines. Unlike the conventional platinum(II) drugs, PhenPt(II) is more likely to bind the N7 adenosine base of DNA in situ, and consequently resulting in a unique cellular response profile and unusual potency. However, since this drug is positively charged, it can easily bind to plasma protein that leads to rapid systematic clearance and deleterious toxicities, which greatly limits its in vivo application. Herein, a lipophilic phenanthriplatin (PhenPt(IV)) prodrug is synthesized. To further reduce its toxicity, a negatively charged polymer P1 with reduction responsiveness is assembled with PhenPt(IV) to form PhenPt(IV) NPs. In comparison to cisplatin, PhenPt(IV) NPs exhibit up to 30 times greater in vitro potency against various cancer cell lines. Additionally, in vivo, no obvious side effect is found on PhenPt(IV) NPs. Significant enhancement in tumor accumulation and improvement of drug efficacy in 4T1 tumor model are demonstrated. Taken together, this study provides a promising strategy for the clinical translation of phenanthriplatin.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Profármacos
/
Antineoplásicos
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
Small
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2021
Tipo del documento:
Article