Cyclotriphosphazene-Based Star Copolymers as Structurally Tunable Nanocarriers with Programmable Biodegradability
- Resource Type
- Authors
- Lucie Woldřichová; Michal Pechar; Geoffrey M. Lynn; Lenka Malinová; Richard Laga; Ladislav Androvič; Klaudia Jozefjaková; Dana Kaňková
- Source
- Macromolecules. 54:3139-3157
- Subject
- chemistry.chemical_classification
Polymers and Plastics
Chemistry
Organic Chemistry
02 engineering and technology
Polymer
010402 general chemistry
021001 nanoscience & nanotechnology
01 natural sciences
Combinatorial chemistry
0104 chemical sciences
Nanomaterials
Inorganic Chemistry
chemistry.chemical_compound
Drug delivery
PEG ratio
Materials Chemistry
Copolymer
Methacrylamide
Nanocarriers
0210 nano-technology
Ethylene glycol
- Language
- ISSN
- 1520-5835
0024-9297
Myriad nanocarriers have been developed to improve the therapeutic index of low-molecular-weight drugs for cancer treatment, but many have suboptimal size and/or are too stable for optimal penetration into tumors and their subsequent excretion from the body. To address this challenge, we developed a series of novel nanocarriers based on star polymers consisting of hydrophilic poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) or poly(ethylene glycol) (PEG) polymer arms attached to hexavalent cyclotriphosphazene (CTP)-derived cores through either stable or stimuli-responsive linkers. The star polymers were assembled using either “grafting from” or “grafting onto” approaches and characterized by quantitative arm substitution at the core. The resulting star polymers were precisely defined water-soluble nanomaterials with a suitable hydrodynamic size (∼10–25 nm) for tumor uptake; those with stimuli-responsive linkers exhibited programmable pH- or cathepsin-mediated degradability. Finally, low-molecular-weight drugs—an anthracycline-based cancerostatic and an imidazoquinoline-based immunostimulant—were linked to exemplary CTP-based star polymers to demonstrate their suitability for drug delivery.