Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Kingston, Rhode Island, 02881, USA.
Bioengineering Department, The University of Texas at Arlington, Arlington, Texas, 76019, USA.
Pharm Res. 2022 Nov;39(11):2729-2743. doi: 10.1007/s11095-022-03317-8. Epub 2022 Jun 28.
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.
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.
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).
In all, both formulations hold promise as inherently fluorescent, stimuli-responsive theranostic platforms for passively targeted anti-cancer therapy.
开发两种新型的仅 pH 和 pH-及温度响应的治疗性纳米粒子（NP）制剂，以递送一种抗癌药物，并通过固有荧光跟踪制剂的积累和治疗效果。
通过乳液技术，从可生物降解的光致发光聚合物（BPLP）和碳酸氢钠（SBC）合成 pH 响应制剂，而使用热响应 BPLP 共聚物（TFP）和 SBC 通过自由基共聚合成双重刺激响应制剂。顺铂被用作模型药物并在合成过程中被包封。评估了粒径、表面电荷、形态、pH 依赖性荧光、低临界溶液温度（TFP NPs 仅）、细胞相容性和体外摄取、药物释放动力学和抗癌功效。
虽然所有 BPLP-SBC 和 TFP-SBC 组合都产生了大小在 200-300nm 之间的球形纳米粒子，但选择了最佳的聚合物-SBC 比例进行进一步研究。在这些组合中，发现最佳的 BPLP-SBC 制剂对原代 1 型肺泡上皮细胞（AT1）的细胞相容性高达 100μg/mL，并在 14 天内持续释放药物，呈剂量依赖性摄取，并显著依赖 pH 杀死 A549 癌细胞（pH7.4 时为 72%，pH6.0 时为 24%）。最佳的 TFP-SBC 制剂对 AT1 细胞表现出极好的细胞相容性，高达 500μg/mL，具有持续释放特性、剂量依赖性摄取、pH 依赖性（pH7.4 时为 78%，pH6.0 时为 64%，在 37°C 时）和显著的温度依赖性 A549 癌细胞杀伤（在 37°C 时为 64%，在 pH6.0 时为 41°C 时为 37%）。
总的来说，这两种制剂都有希望成为被动靶向抗癌治疗的固有荧光、刺激响应治疗平台。
