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<p>Engineered nanoparticles represent a cutting-edge advancement in biomedical science. They provide highly adaptable platforms for precise diagnostics, targeted drug delivery, and real-time imaging applications. However, their nanoscale dimensions and physicochemical heterogeneity introduce unique bio–nano-interactions that diverge significantly from bulk material behavior, necessitating rigorous toxicological scrutiny. The unpredictable nature of NP–biological interfaces, particularly at the cellular and molecular levels, poses critical challenges in assessing biocompatibility and long-term safety. This review critically synthesizes current advances in the toxicological profiling of NPs, focusing on mechanistic insights into their cellular and systemic interactions. It also explores engineering strategies aimed at mitigating adverse effects without compromising functional performance in biomedical contexts. We examine a multidisciplinary corpus of studies utilizing high-content screening, omics-driven toxicogenomics, real-time cell analysis systems, and physiologically relevant 3D tissue models. Emphasis is placed on correlating NP parameters core composition, size, shape anisotropy, surface charge, functional ligands, and corona formation with cellular responses, such as endocytotic trafficking, intracellular ROS generation, lysosomal destabilization, epigenetic modifications, and immunogenicity. Toxicological outcomes are shown to be highly dependent on NP physicochemical properties and biological milieu. Surface engineering with zwitterionic, PEGylated, or cell membrane-mimetic coatings significantly reduces opsonization, prolongs circulation time, and attenuates inflammatory cascades. Machine learning-based models are helping scientists better predict the toxicity of nanoparticles before testing them in the lab. By combining tools like QSAR modeling, nanoinformatics, and systems toxicology, researchers are improving how they evaluate the safety of nanoparticles. Future research should prioritize predictive, mechanism-based frameworks, and adaptive design principles. The convergence of nanotechnology and precision toxicology will be significant in advancing the translational potential of nanoparticles while ensuring biosafety. </p>

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A Comprehensive Review of Toxicological Evaluations of NPs and Their Optimization for Biomedical Applications

  • 期刊论文

  • 发表日期：

    2025年8月22日

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  • Hussan ibne Shoukani,
  • Khudija tul Kubra,
  • Sobia Nisa,
  • Abdullah,
  • Sabahat Qumar,
  • Sabayyel Hassan,
  • Nimra Nasir,
  • Muhammad Raheel Awan

摘要

Engineered nanoparticles represent a cutting-edge advancement in biomedical science. They provide highly adaptable platforms for precise diagnostics, targeted drug delivery, and real-time imaging applications. However, their nanoscale dimensions and physicochemical heterogeneity introduce unique bio–nano-interactions that diverge significantly from bulk material behavior, necessitating rigorous toxicological scrutiny. The unpredictable nature of NP–biological interfaces, particularly at the cellular and molecular levels, poses critical challenges in assessing biocompatibility and long-term safety. This review critically synthesizes current advances in the toxicological profiling of NPs, focusing on mechanistic insights into their cellular and systemic interactions. It also explores engineering strategies aimed at mitigating adverse effects without compromising functional performance in biomedical contexts. We examine a multidisciplinary corpus of studies utilizing high-content screening, omics-driven toxicogenomics, real-time cell analysis systems, and physiologically relevant 3D tissue models. Emphasis is placed on correlating NP parameters core composition, size, shape anisotropy, surface charge, functional ligands, and corona formation with cellular responses, such as endocytotic trafficking, intracellular ROS generation, lysosomal destabilization, epigenetic modifications, and immunogenicity. Toxicological outcomes are shown to be highly dependent on NP physicochemical properties and biological milieu. Surface engineering with zwitterionic, PEGylated, or cell membrane-mimetic coatings significantly reduces opsonization, prolongs circulation time, and attenuates inflammatory cascades. Machine learning-based models are helping scientists better predict the toxicity of nanoparticles before testing them in the lab. By combining tools like QSAR modeling, nanoinformatics, and systems toxicology, researchers are improving how they evaluate the safety of nanoparticles. Future research should prioritize predictive, mechanism-based frameworks, and adaptive design principles. The convergence of nanotechnology and precision toxicology will be significant in advancing the translational potential of nanoparticles while ensuring biosafety.