Dynamic intracellular exchange of nanomaterials’ protein corona perturbs proteostasis and remodels cell metabolism

Cai, Rong; Ren, Jiayu; Guo, Mengyu; Wei, Taotao; Liu, Ying; Xie, Chunyu; Zhang, Peng; Guo, Zhiling; Chetwynd, Andrew J.; Ke, Pu Chun; Lynch, Iseult; Chen, Chunying

doi:10.1073/pnas.2200363119

Cited by 75 publications

(56 citation statements)

References 59 publications

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“…The composition of the corona confers biological identity to NMs and probably directs further interactions with proteins, cells, tissues, etc. 3 , 4 . The formation and evolution of protein corona are thermodynamic and kinetics processes, during which dynamic exchange of corona components is based on different abundance and diffusion rates of proteins, and varying affinities of different proteins binding to the NMs.…”

Section: Introductionmentioning

confidence: 99%

In situ analysis of nanoparticle soft corona and dynamic evolution

et al. 2022

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How soft corona, the protein corona’s outer layer, contributes to biological identity of nanomaterials is largely because capturing protein composition of the soft corona in situ remains challenging. We herein develop an in situ Fishing method that can monitor the dynamic formation of protein corona on ultra-small chiral Cu2S nanoparticles (NPs) allowing us to directly separate and identify the corona protein composition. Our method detects spatiotemporal processes in the evolution of hard and soft coronas on chiral NPs, revealing subtle differences in NP − protein interactions even within several minutes. This study highlights the importance of in situ and dynamic analysis of soft/hard corona, provides insights into the role of soft corona in mediating biological responses of NPs, and offers a universal strategy to characterize soft corona to guide the rational design of biomedical nanomaterials.

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Section: Introductionmentioning

confidence: 99%

In situ analysis of nanoparticle soft corona and dynamic evolution

et al. 2022

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“…The formation of protein crowns will reshape the metabolic behavior of nanocarriers in vivo, causing non-specific phagocytosis while triggering a series of side effects including autoimmune response, apoptosis or necrosis and inflammation. In recent years, Chen et al 47 identified the protein corona effect also restricted the delivery efficiency of nanomedicine and affected drug release in animals, which might also contribute to the poor therapeutic effect.…”

Section: Discussionmentioning

confidence: 99%

Multifunctional Nanosnowflakes for T1-T2 Double-Contrast Enhanced MRI and PAI Guided Oxygen Self-Supplementing Effective Anti-Tumor Therapy

Lv¹,

Kan²,

Luo³

et al. 2022

IJN

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Introduction: Accurate tumor diagnosis is essential to achieve the ideal therapeutic effect. However, it is difficult to accurately diagnose cancer using a single imaging method because of the technical limitations. Multimodal imaging plays an increasingly important role in tumor treatment. Photodynamic therapy (PDT) has received widespread attention in tumor treatment due to its high specificity and controllable photocytotoxicity. Nevertheless, PDT is susceptible to tumor microenvironment (TME) hypoxia, which greatly reduces the therapeutic effect of tumor treatment. Methods: In this study, a novel multifunctional nano-snowflake probe (USPIO@MnO 2 @Ce6, UMC) for oxygen-enhanced photodynamic therapy was developed. We have fabricated the honeycomb-like MnO 2 to co-load chlorin e6 (Ce6, a photosensitizer) and ultrasmall superparamagnetic iron oxide (USPIO, T1-T2 double contrast agent). Under the high H 2 O 2 level of tumor cells, UMC efficiently degraded and triggered the exposure of photosensitizers to the generated oxygen, accelerating the production of reactive oxygen species (ROS) during PDT. Moreover, the resulting USPIO and Mn 2+ allow for MR T1-T2 imaging and transformable PAI for multimodal imaging-guided tumor therapy.Results: TEM and UV-vis spectroscopy results showed that nano-snowflake probe (UMC) was successfully synthesized, and the degradation of UMC was due to the pH/ H 2 O 2 responsive properties. In vitro results indicated good uptake of UMC in 4T-1 cells, with maximal accumulation at 4 h. In vitro and in vivo experimental results showed their imaging capability for both T1-T2 MR and PA imaging, providing the potential for multimodal imaging-guided tumor therapy. Compared to the free Ce6, UMC exhibited enhanced treatment efficiency due to the production of O 2 with the assistance of 660 nm laser irradiation. In vivo experiments confirmed that UMC achieved oxygenated PDT under MR/PA imaging guidance in tumor-bearing mice and significantly inhibited tumor growth in tumor-bearing mice, exhibiting good biocompatibility and minimal side effects. Conclusion:The multimodal imaging contrast agent (UMC) not only can be used for MR and PA imaging but also has oxygenenhanced PDT capabilities. These results suggest that UMC may have a good potential for further clinical application in the future.

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“…In an environmental context, pristine nanomaterials transform and obtain a corona of biomolecules, such as proteins, which shields the identity of a nanoparticle, possibly affecting the long circulation and targeting efficiency. 39 Although the orientation and conformation of bound proteins are thought to be strong indicators of cellular uptake, the nature of proteins, characterization of corona composition, and geometry of the nanomaterial will also play key roles in nano−bio interactions.…”

Section: Protein Corona: Passive Adsorption and Endogeneous Regulationmentioning

confidence: 99%

Engineering Nano–Bio Interfaces from Nanomaterials to Nanomedicines

et al. 2022

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The nano−bio interface refers to the physical interface between the biological system and nanoscale surface topography, functioning as the barrier between two phases where critical reactions occur. In the last two decades, advances in nanofabrication techniques have heralded a new research area utilizing precisely engineered surfaces and structures to control cell cycles, pathways of metabolism, immune responses, and so forth. At the cellular level, engineered nanomaterials (ENMs) with typical surfaces and structures have been shown to actively affect biological responses, such as stimulating macrophage polarization, monitoring reduction−oxidation equilibrium, and manipulating protease activities via tunable nano−bio interactions. In this Account, we outline our recent progress in surface engineering and structural engineering to improve nano−bio interactions and the performance of nanomedicine. To regulate nanomaterial−molecule and nanomaterial−membrane interactions, we summarize the classical types of nano−bio interaction, extract the essential parameters in nanomaterial surface engineering and structural engineering, and propose effective techniques of surface engineering and structural engineering. We start with identifying the types of dominant interactions between nanomedicines and vital biomolecules: nanonucleic acids, nanoproteins, and nanomembranes. The surface engineering strategies of nano−bio interface tailoring are then arranged into four perspectives: the protein corona (the two modes of protein corona formation and their impacts on altering the affinity profiles of nanomaterials to biological systems), thermoresponsive polymers in superficial modification (passive activation by in situ gelation and active regulation by photothermal conversion), stimulus-induced bonding groups (mediation of nanoparticle aggregation to balance the penetration depth and longterm retention), and inherent surface properties (surface roughness for maximized nano−bio adhesion, surface charge for electrostatic attraction and biological barrier penetration of nanoparticles, and skeleton oxidation to boost nano−bio hydrogen bonding). Structural engineering of nanomaterials occurs by remote manipulation through electron-transfer facilitation (doping, heterojunction, defects, and vacancies) of the nano−bio interaction, following multifaceted solutions that combine multiple surface engineering plans. The scopes and limitation section discusses the prospective problems that can occur when nanomaterials/ nanomedicines interact in biological contexts. Because both clinical and laboratory studies have shown the influence of surface topological features on biological responses, the feedback of biological systems to different topographical features of nanomaterials/ nanomedicines is essential for us to comprehend the nano−bio interface at the relevant nanometer length scale. For on-demand nano−bio interactions, the discovery provides insight into the rational design of nanomaterials/nanomedicines.

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Dynamic intracellular exchange of nanomaterials’ protein corona perturbs proteostasis and remodels cell metabolism

Cited by 75 publications

References 59 publications

In situ analysis of nanoparticle soft corona and dynamic evolution

In situ analysis of nanoparticle soft corona and dynamic evolution

Multifunctional Nanosnowflakes for T1-T2 Double-Contrast Enhanced MRI and PAI Guided Oxygen Self-Supplementing Effective Anti-Tumor Therapy

Engineering Nano–Bio Interfaces from Nanomaterials to Nanomedicines

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