通过光散射和机器学习解决药物递送系统中纳米载体的异质混合物问题。
Toward Resolving Heterogeneous Mixtures of Nanocarriers in Drug Delivery Systems through Light Scattering and Machine Learning.
作者信息
Mancoo Allan, Silva Mariana, Lopes Claudia, Loureiro Maria, Pinto Vanessa, Ramalho João F C B, Carvalho Patricia, Gouveia Carlos A J, Rocha Sara, Bordeira Sandro M P, Sampaio Paula M, Turpin Alex, Gersen Henkjan, Mumtaz Mehak
机构信息
iLoF-Intelligent Lab on Fiber, Rua de Godim 389, 4300 Porto, Portugal.
Departamento de Bioquímica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal.
出版信息
ACS Nano. 2025 Jan 21;19(2):2388-2404. doi: 10.1021/acsnano.4c12963. Epub 2025 Jan 8.
Nanocarriers (NCs) have emerged as a revolutionary approach in targeted drug delivery, promising to enhance drug efficacy and reduce toxicity through precise targeting and controlled release mechanisms. Despite their potential, the clinical adoption of NCs is hindered by challenges in their physicochemical characterization, essential for ensuring drug safety, efficacy, and quality control. Traditional characterization methods, such as dynamic light scattering and nanoparticle tracking analysis, offer limited insights, primarily focusing on particle size and concentration, while techniques like high-performance liquid chromatography and mass spectrometry are hampered by extensive sample preparation, high costs, and potential sample degradation. Addressing these limitations, this work presents a cost-effective methodology leveraging light scattering and optical forces, combined with machine learning algorithms, to characterize polydisperse nanoparticle mixtures, including lipid-based NCs. We prove that our approach provides quantification of the relative concentration of complex nanoparticle suspensions by detecting changes in refractive index and polydispersity without extensive sample preparation or destruction, offering a high-throughput solution for NC characterization in drug delivery systems. Experimental validation demonstrates the method's efficacy in characterizing commercially available synthetic nanoparticles and Doxoves, a liposomal formulation of Doxorubicin used in cancer treatment, marking a significant advancement toward reliable, noninvasive characterization techniques that can accelerate the clinical translation of nanocarrier-based therapeutics.
纳米载体(NCs)已成为靶向给药领域的一种革命性方法,有望通过精确靶向和控释机制提高药物疗效并降低毒性。尽管具有潜力,但NCs在临床应用中受到其物理化学表征方面挑战的阻碍,而物理化学表征对于确保药物安全性、疗效和质量控制至关重要。传统的表征方法,如动态光散射和纳米颗粒跟踪分析,提供的见解有限,主要侧重于粒径和浓度,而高效液相色谱和质谱等技术则受到样品前处理繁琐、成本高以及潜在样品降解的困扰。为了解决这些局限性,本研究提出了一种经济高效的方法,利用光散射和光镊技术,并结合机器学习算法,来表征包括脂质基NCs在内的多分散纳米颗粒混合物。我们证明,我们的方法通过检测折射率和多分散性的变化,无需进行大量样品前处理或破坏,即可对复杂纳米颗粒悬浮液的相对浓度进行定量,为药物递送系统中的NC表征提供了一种高通量解决方案。实验验证表明,该方法在表征市售合成纳米颗粒和Doxoves(一种用于癌症治疗的阿霉素脂质体制剂)方面具有有效性,这标志着朝着可靠、无创的表征技术迈出了重要一步,这种技术可以加速基于纳米载体的治疗药物的临床转化。