One of the unmet challenges in nanotechnology is to understand and establish the relationship between physicochemical properties of nanoparticles (NPs) and its biological interactions (bio-nano interactions). However, we are still far from assessing the biofate of NPs in a clear and unquestionable manner. Recent developments in the area of bio-nano interface and the understanding of protein corona (PC) has brought new insight in predicting biological interactions of NPs. PC refers to the spontaneous formation of an adsorbed layer of biomolecules on the surface of NPs in a biological environment. PC formation involves the spatiotemporal interplay of an intricate network of biological, environmental and particle characteristics. NPs with its PC can be viewed as a biological entity, which interacts with cells and barriers in a biological system. Recent studies on the bio-nano interface have revealed biological signatures that participate in cellular and physiological bioprocesses and control the biofate and toxicity of NPs. The ability of in-vitro derived parameters to forecast in-vivo consequences by developing a mathematical model forms the basis of in-vitro in-vivo correlation (IVIVC). Understanding the effect of bio-nano interactions on the biological consequences of NPs at the cellular and physiological level can have a direct impact on the translation of future nanomedicines and can lead to the ultimate goal of developing a mathematical IVIVC model. The review summarizes the emerging paradigms in the field of bio-nano-interface which clearly suggests an urgent need to revisit existing protocols in nanotechnology for defining the physicochemical correlates of bio-nano interactions.

纳米技术中尚未解决的挑战之一是了解并建立纳米颗粒（NPs）的物理化学性质与其生物学相互作用（生物-纳米相互作用）之间的关系。但是，我们离以清晰明确的方式评估NP的生物命运还很遥远。生物-​​纳米界面领域的最新发展以及对蛋白质电晕（PC）的理解为预测NP的生物相互作用带来了新的见识。PC是指在生物环境中NPs表面上自然形成的生物分子吸附层。PC的形成涉及生物，环境和颗粒特征的复杂网络的时空相互作用。具有其PC的NP可被视为生物实体，它与生物系统中的细胞和屏障相互作用。关于生物-纳米界面的最新研究已经揭示了参与细胞和生理生物过程并控制NP的生物命运和毒性的生物特征。体外衍生参数通过建立数学模型来预测体内后果的能力构成了体外体内相关性（IVIVC）的基础。在细胞和生理水平上了解生物-纳米相互作用对NP的生物学后果的影响可能对未来纳米药物的翻译产生直接影响，并可能导致开发数学IVIVC模型的最终目标。该综述总结了生物-纳米界面领域中正在出现的范式，这明确表明迫切需要重新审视纳米技术中用于定义生物-纳米相互作用的理化相关性的现有协议。