Crystalline Nanoparticles of Water-Soluble Covalent Basket Cages (CBCs) for Encapsulation of Anticancer Drugs.
Angew Chem Int Ed Engl
; 62(33): e202306722, 2023 08 14.
Article
de En
| MEDLINE
| ID: mdl-37332078
ABSTRACT
We herein describe the preparation, assembly, recognition characteristics, and biocompatibility of novel covalent basket cage CBC-11, composed of four molecular baskets linked to four trivalent aromatic amines through amide groups. The cage is tetrahedral in shape and similar in size to small proteins (Mw =8637â
g/mol) with a spacious nonpolar interior for accommodating multiple guests. While 24â
carboxylates at the outer surface of CBC-11 render it soluble in aqueous phosphate buffer (PBS) at pH=7.0, the amphiphilic nature prompts its assembly into nanoparticles (d=250â
nm, DLS). Cryo-TEM examination of nanoparticles revealed their crystalline nature with wafer-like shapes and hexagonally arranged cages. Nanoparticulate CBC-11 traps anticancer drugs irinotecan and doxorubicin, with each cage binding up to four drug molecules in a non-cooperative manner. The inclusion complexation resulted in nanoparticles growing in size and precipitating. In media containing mammalian cells (HCTâ
116, human colon carcinoma), the IC50 value of CBC-11 was above 100â
µM. While this work presents the first example of a large covalent organic cage operating in water at the physiological pH and forming crystalline nanoparticles, it also demonstrates its biocompatibility and potential to act as a polyvalent binder of drugs for their sequestration or delivery.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Nanoparticules
/
Antinéoplasiques
Limites:
Animals
/
Humans
Langue:
En
Journal:
Angew Chem Int Ed Engl
Année:
2023
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique