Biodegradable and Inherently Fluorescent pH-Responsive Nanoparticles for Cancer Drug Delivery
Document Type
Article
Date of Original Version
1-1-2022
Abstract
Purpose: The development of two novel pH-only and pH- and thermo-responsive theranostic nanoparticle (NP) formulations to deliver an anticancer drug and track the accumulation and therapeutic efficacy of the formulations through inherent fluorescence. Methods: A pH-responsive formulation was synthesized from biodegradable photoluminescent polymer (BPLP) and sodium bicarbonate (SBC) via an emulsion technique, while a thermoresponsive BPLP copolymer (TFP) and SBC were used to synthesize a dual-stimuli responsive formulation via free radical co-polymerization. Cisplatin was employed as a model drug and encapsulated during synthesis. Size, surface charge, morphology, pH-dependent fluorescence, lower critical solution temperature (LCST; TFP NPs only), cytocompatibility and in vitro uptake, drug release kinetics and anticancer efficacy were assessed. Results: While all BPLP-SBC and TFP-SBC combinations produced spherical nanoparticles of a size between 200-300 nm, optimal polymer-SBC ratios were selected for further study. Of these, the optimal BPLP-SBC formulation was found to be cytocompatible against primary Type-1 alveolar epithelial cells (AT1) up to 100 μg/mL, and demonstrated sustained drug release over 14 days, dose-dependent uptake, and marked pH-dependent A549 cancer cell killing (72 vs. 24% cell viability, at pH 7.4 vs. 6.0). The optimal TFP-SBC formulation showed excellent cytocompatibility against AT1 cells up to 500 μg/mL, sustained release characteristics, dose-dependent uptake, pH-dependent (78% at pH 7.4 vs. 64% at pH 6.0 at 37°C) and marked temperature-dependent A549 cancer cell killing (64% at 37°C vs. 37% viability at pH 6.0, 41°C). Conclusions: In all, both formulations hold promise as inherently fluorescent, stimuli-responsive theranostic platforms for passively targeted anti-cancer therapy. Graphical Abstract: [Figure not available: see fulltext.].
Publication Title, e.g., Journal
Pharmaceutical Research
Citation/Publisher Attribution
Perera, Kalindu, Dat X. Nguyen, Dingbowen Wang, Aneetta E. Kuriakose, Jian Yang, Kytai T. Nguyen, and Jyothi U. Menon. "Biodegradable and Inherently Fluorescent pH-Responsive Nanoparticles for Cancer Drug Delivery." Pharmaceutical Research (2022). doi: 10.1007/s11095-022-03317-8.