Biodegradable and Inherently Fluorescent pH-Responsive Nanoparticles for Cancer Drug Delivery.
Pharm Res
; 39(11): 2729-2743, 2022 Nov.
Article
em En
| MEDLINE
| ID: mdl-35764754
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nanopartículas
/
Neoplasias
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article