Crystalline Nanoparticles of Water-Soluble Covalent Basket Cages (CBCs) for Encapsulation of Anticancer Drugs

Vageesha W. Liyana Gunawardana, Carson Ward, Han Wang, Joseph H. Holbrook, Emily R. Sekera, Honggang Cui, Amanda B. Hummon, Jovica D. Badjić

Research output: Contribution to journalArticlepeer-review

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=8637 g/mol) with a spacious nonpolar interior for accommodating multiple guests. While 24 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=250 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 (HCT 116, human colon carcinoma), the IC50 value of CBC-11 was above 100 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.

Original languageEnglish (US)
Article numbere202306722
JournalAngewandte Chemie - International Edition
Volume62
Issue number33
DOIs
StatePublished - Aug 14 2023
Externally publishedYes

Keywords

  • Anticancer Drugs
  • Covalent Organic Cages
  • Drug Delivery
  • Host-Guest Chemistry
  • Sequestration

ASJC Scopus subject areas

  • General Chemistry
  • Catalysis

Fingerprint

Dive into the research topics of 'Crystalline Nanoparticles of Water-Soluble Covalent Basket Cages (CBCs) for Encapsulation of Anticancer Drugs'. Together they form a unique fingerprint.

Cite this