Blood circulation of soft nanomaterials is governed by dynamic remodeling of protein opsonins at nano-biointerface

Abbina, Srinivas; Takeuchi, Lily E.; Anilkumar, Parambath; Yu, Kai; Rogalski, Jason C.; Shenoi, Rajesh A.; Constantinescu, Iren; Kizhakkedathu, Jayachandran N.

doi:10.1038/s41467-020-16772-x

Cited by 68 publications

(53 citation statements)

References 35 publications

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“…Coagulation and complement proteins that were adsorbed initially on the surface of SMPN-1 were released during the circulation and accumulation of lipoproteins and acute phase reactants happened over 48 h on the surface. In contrast, short-circulating SMPN-9 had high abundance of complement proteins and acute phase reactants at 48 h. Adapted with permission from Abbina et al (2020) . (C) PC influenced the biodistribution of G-rich and poly-T SNAs.…”

Section: Impacts Of In Vivo Pc On Biobehaviors Of mentioning

confidence: 99%

“…The fluctuating PEG segments reduce protein binding affinity with ENPs, rather than the total amount of adsorbed proteins, which could prolong circulation time. Except for PEG, soft single molecule polymer nanomaterials (SMPNs) which were prepared with macroinitiator, hyperbranched polyglycerol (HPG), was also presented to enhance circulation time in blood ( Figure 1B ; Abbina et al, 2020 ). PC composition of ENPs at the biointerface is highly dynamic and remodeled while in circulation.…”

Section: Impacts Of In Vivo Pc On Biobehaviors Of mentioning

confidence: 99%

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In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

Bai

Wang

et al. 2021

Front. Bioeng. Biotechnol.

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Understanding the basic interactions between engineered nanoparticles (ENPs) and biological systems is essential for evaluating ENPs’ safety and developing better nanomedicine. Profound interactions between ENPs and biomolecules such as proteins are inevitable to occur when ENPs are administered or exposed to biological systems, for example, through intravenous injection, oral, or respiration. As a key component of these interactions, protein corona (PC) is immediately formed surrounding the outlayer of ENPs. PC formation is crucial because it gives ENPs a new biological identity by altering not only the physiochemical properties, but also the biobehaviors of ENPs. In the past two decades, most investigations about PC formation were carried out with in vitro systems which could not represent the true events occurring within in vivo systems. Most recently, studies of in vivo PC formation were reported, and it was found that the protein compositions and structures were very different from those formed in vitro. Herein, we provide an in-time review of the recent investigations of this in vivo PC formation of ENPs. In this review, commonly used characterization methods and compositions of in vivo PC are summarized firstly. Next, we highlight the impacts of the in vivo PC formation on absorption, blood circulation, biodistribution, metabolism, and toxicity of administered ENPs. We also introduce the applications of modulating in vivo PC formation in nanomedicine. We further discuss the challenges and future perspectives.

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Section: Impacts Of In Vivo Pc On Biobehaviors Of mentioning

confidence: 99%

Section: Impacts Of In Vivo Pc On Biobehaviors Of mentioning

confidence: 99%

In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

Bai

Wang

et al. 2021

Front. Bioeng. Biotechnol.

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“…This could perhaps be attributed to the long duration of protein corona formation in vitro , which likened to a long circulation time in the blood. Consequently, the long circulation time has been shown previously to eliminate the presence of opsonin on the surface due to continuous remodeling of proteins occurring . However, further studies need to be conducted to demonstrate if these serum-coated NRs remain stealthy and to determine the optimal length of circulation in the blood to retain its stealth properties.…”

Section: Resultsmentioning

confidence: 99%

“…Consequently, the long circulation time has been shown previously to eliminate the presence of opsonin on the surface due to continuous remodeling of proteins occurring. 75 However, further studies need to be conducted to demonstrate if these serum-coated NRs remain stealthy and to determine the optimal length of circulation in the blood to retain its stealth properties. Low levels of SC5b-9 concentration were also found in human sera containing NR-Cit (369.4 ± 48.4 ng/mL SC5b-9), thus suggesting the ability of NR-Cit to avoid interacting with complement proteins, although they presented greater interaction with the RBCs to induce their aggregation.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Stealthiness and Hematocompatibility of Gold Nanoparticles with Pre-Formed Protein Corona

2021

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Studies have established that a serum protein corona pre-formed around gold nanorods (NRs) could be exploited for loading photosensitizers and chemotherapeutics to result in efficient cell kill in vitro with an extremely low dose. In this study, we further demonstrated that pre-forming a serum protein corona (PC) around citrate-capped NRs (NR-Cit) to form NR-PC conferred them stealth property and high hematocompatibility similar to the common strategy of PEGylating NRs, which would otherwise not be able to evade the immune system. Specifically, the NR-PC caused minimal complement activation with significantly lower formation of the terminal complement complex SC5b-9 measured in human serum containing NR-PC, and this resulted in low uptake by phagocytic U937 monocytes of 5.9% of the initial gold dose compared to 55.8% of NR-Cit. In addition, NR-PC exhibited very low hemolytic activity of less than 0.2% hemolysis with no observable effect on RBC morphology as opposed to 0.6% for NR-Cit at the same concentration of 1 nM NRs. Furthermore, we showed that the high hematocompatibility and stealth property of NR-PC were maintained even after the loading of small molecules, photosensitizer Chlorine e6 (Ce6), into the protein corona, thus further establishing the potential clinical relevance of exploiting the inevitably formed serum protein corona on nanoparticles as an effective delivery vector for small molecular therapeutics.

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“…For instance, potential toxicity and immune rejection of nanomaterials remain to be further studied. In addition, in the process of transport in blood, various proteins may be adsorbed on the nanomaterials, forming “protein corona,” to affect their stability and targeting ability [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Responsive Dual-Targeting Exosome as a Drug Carrier for Combination Cancer Immunotherapy

et al. 2021

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Recently, combination immunotherapy, which incorporates the activation of the immune system and inhibition of immune escape, has been proved to be a new powerful strategy for more efficient tumor suppression compared to monotherapy. However, the major challenge is how to integrate multiple immune drugs together and efficiently convey these drugs to tumor sites. Although a variety of nanomaterials have been exploited as carriers for targeting tumor issues and the delivery of multiple drugs, their potential toxicity, immune rejection, and stability are still controversial for clinical application. Here, we proposed endogenic exosomes as drug carriers to deliver two antibodies acting as tumor-targeting molecules and block checkpoint inhibitors with specific response to the tumor microenvironment and costimulatory molecules for further improvement of therapeutic effect. The versatile exosomes exhibit excellent biocompatibility and provide a combination immunotherapy platform with synergistic advantages of activation of immune response and inhibition of immune escape.

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Blood circulation of soft nanomaterials is governed by dynamic remodeling of protein opsonins at nano-biointerface

Cited by 68 publications

References 35 publications

In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

In vivo Protein Corona Formation: Characterizations, Effects on Engineered Nanoparticles’ Biobehaviors, and Applications

Stealthiness and Hematocompatibility of Gold Nanoparticles with Pre-Formed Protein Corona

Responsive Dual-Targeting Exosome as a Drug Carrier for Combination Cancer Immunotherapy

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