Kadambari, Kadambari (2025) Development of Dual Acid/Light-Responsive Imine-based Polymeric Nanocarriers for Drug Delivery. PhD thesis, Concordia University.
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Abstract
Development of Dual Acid/Light-Responsive Imine-based Polymeric Nanocarriers for Drug Delivery
Kadambari Kadambari, Ph.D.
Concordia University, 2025
Stimuli-responsive degradable amphiphilic block copolymers (SRD-ABPs) have been extensively explored as promising building blocks in the construction of smart nanoassemblies exhibiting controlled/enhanced release of encapsulated molecules including therapeutics. A recent advance involves the development of dual SRD-ABPs designed with cleavable linkages responsive to two stimuli, typically acidic pH and light. Herein, we report a new approach to achieve dual acidic pH/light responses with a single labile linkage employing conjugated benzoic imine chemistry. As a proof-of-concept, a well-defined poly(ethylene glycol)-based SRD-ABP containing conjugated benzoic imine pendants in the hydrophobic block was synthesized by reversible deactivation radical polymerization and post-polymerization modification. The synthesized copolymer self-assembled in aqueous solution to form colloidally stable nanoassemblies, consisting of acid/light-degradable hydrophobic cores surrounded with hydrophilic coronas. Upon exposure to acidic pH and UV/visible light, the nanoassemblies degraded through change in hydrophobic/hydrophilic balance of micelle cores.
Extending this strategy, conjugated aromatic imine bonds are unique in their ability to respond to both acidic pH through acid-catalyzed hydrolysis and to visible light through photo-induced E/Z isomerization, thus enabling dual responsiveness with a single chemical group. We report a robust strategy to fabricate core-crosslinked nanogels bearing extended conjugate aromatic imine linkages, exhibiting controlled degradation in response to dual acidic pH and visible light. The strategy involves pre-crosslinking a poly(ethylene glycol)-based block copolymer bearing reactive imidazole pendants with a diol crosslinker bearing extended conjugate aromatic imine, followed by dispersion of the crosslinked polymer in aqueous solution. The fabricated nanogels are non-cytotoxic, colloidally stable, and capable of encapsulating curcumin. They exhibit controlled/enhanced release of curcumin in acidic pH and
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under visible light irradiation, with synergistic release under dual stimuli. Furthermore, curcumin-loaded nanogels reduce cell viability in a controlled manner, unlike the free drug.
We further report aqueous nanocolloids based on step-growth conjugated poly(benzoic imine)s (M-PCs) bearing aromatic imine bonds on the backbones with absorption in the visible range (λ = 420 nm). These nanocolloids, fabricated with polymeric stabilizers, display excellent colloidal stability in physiological environments. They undergo disintegration upon degradation of the M-PC backbone under acidic pH and visible light irradiation. These results demonstrate the potential of extended aromatic imine-based nanoplatforms for dual acid/visible light-responsive therapeutic delivery with controlled/enhanced release of encapsulated drugs.
| Divisions: | Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry |
|---|---|
| Item Type: | Thesis (PhD) |
| Authors: | Kadambari, Kadambari |
| Institution: | Concordia University |
| Degree Name: | Ph. D. |
| Program: | Chemistry |
| Date: | 16 May 2025 |
| Thesis Supervisor(s): | Oh, Jung Kwon |
| ID Code: | 995722 |
| Deposited By: | Kadambari Kadambari |
| Deposited On: | 04 Nov 2025 15:22 |
| Last Modified: | 04 Nov 2025 15:22 |
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