Why nanoparticles prefer liver macrophage cell uptake in vivo

Ngo, Wayne; Ahmed, Sara; Blackadar, Colin; Bussin, Bram; Ji, Qin; Mladjenovic, Stefan M.; Sepahi, Zahra; Chan, Warren C. W.

doi:10.1016/j.addr.2022.114238

Cited by 108 publications

(56 citation statements)

References 152 publications

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“…5A). After 24 h circulation, the liver showed the highest fluorescence intensity, since liver is the major organ to trap, metabolize, and eliminate nanoparticles [58]. Importantly, compared with free Ce6, CH/ DF showed notably bright fluorescence at tumor site.…”

Section: Targeting Delivery Of Ch/df For Synergistic Anti-tumor Thera...mentioning

confidence: 98%

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

et al. 2022

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Photodynamic therapy (PDT) has emerged as a promising tumor treatment method via light-triggered generation of reactive oxygen species (ROS) to kill tumor cells. However, the efficacy of PDT is usually restricted by several biological limitations, including hypoxia, excess glutathione (GSH) neutralization, as well as tumor resistance. To tackle these issues, herein we developed a new kind of DNA nanozyme to realize enhanced PDT and synergistic tumor ferroptosis. The DNA nanozyme was constructed via rolling circle amplification, which contained repeat AS1411 G quadruplex (G4) units to form multiple G4/hemin DNAzymes with catalase-mimic activity. Both hemin, an iron-containing porphyrin cofactor, and chlorine e6 (Ce6), a photosensitizer, were facilely inserted into G4 structure with high efficiency, achieving in-situ catalytic oxygenation and photodynamic ROS production. Compared to other self-oxygen-supplying tools, such DNA nanozyme is advantageous for high biological stability and compatibility. Moreover, the nanostructure could achieve tumor cells targeting internalization and intranuclear transport of Ce6 by virtue of specific nucleolin binding of AS1411. The nanozyme could catalyze the decomposition of intracellular H 2 O 2 into oxygen for hypoxia relief as evidenced by the suppression of hypoxia-inducible factor-1α (HIF-1α), and moreover, GSH depletion and cell ferroptosis were also achieved for synergistic tumor therapy. Upon intravenous injection, the nanostructure could effectively accumulate into tumor, and impose multi-modal tumor therapy with excellent biocompatibility. Therefore, by integrating the capabilities of O 2 generation and GSH depletion, such DNA nanozyme is a promising nanoplatform for tumor PDT/ferroptosis combination therapy.

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Section: Targeting Delivery Of Ch/df For Synergistic Anti-tumor Thera...mentioning

confidence: 98%

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

et al. 2022

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“…Whereas the negatively charged PS NCs are cleared rapidly, as is observed for other negatively charged NCs. [17][18][19] These findings provide design insight for nanoformulations and further clarity into key parameters impacting nano-bio interactions.…”

Section: Experimental Designmentioning

confidence: 85%

“…The development of a negative charge in vivo would be expected to drive uptake by macrophages in the liver and spleen, which typically produces the rapid clearance that we observed for PS-iFNP-NCs. 18,19…”

Section: Formulation Effects On Ifnp-nc Surface Properties and Stabilitymentioning

confidence: 99%

Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics

Markwalter¹,

Wang²,

Sharaf³

et al. 2022

Precision Nanomedicine

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Nanocarriers encapsulating nucleic acids or protein therapeutics are important tools for modulating biodistribution and enhancing intracellular delivery of biologics. We have recently developed inverse Flash NanoPrecipitation (iFNP), demonstrating its effectiveness in encapsulating biologics at high loadings and encapsulation efficiency. Here, we present the biodistribution of two iFNP nanocarriers using 64Cu positron emission tomography imaging in a murine adenocarcinoma xenograft model characterized by elevated macrophage content. Two nanocarriers with similar sizes and surfaces were prepared. iFNP produces core-shell-corona nanocarriers where the hydrophobic shell layer in one case was poly(lactic acid) (PLA), and the other nanocarrier shell was poly(styrene) (PS). While the expectation was that the biodistribution and clearance of both nanocarriers would be similar, it was found that the clearance of the PS nanocarrier oc-curred in less than 3 hours while the PLA nanocarrier exhibited sustained circulation times. The mechanism of nanocarrier instability for the PS shell nanocarrier manifests as the development of a negative surface charge due to the exposure of the anionic nanocarrier inner core. The stable PLA-based formulation exhibited circulation times greater than 24 hours and enhanced accumu-lation in the lymphatics and the tumor relative to the unstable formulation. The novel mecha-nism of encapsulation by iFNP motivates the fundamental studies on nanoparticle biodistribu-tion reported here.

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“…The unique organ structure and blood flow characteristics facilitate the aggregation of nanoparticles in reticuloendothelial system (RES) organs and reduce the delivery efficiency of nanoparticles. The liver is the largest organ of RES, which ingests a large proportion of nanoparticles [ 7 ]. At the same time, most nanoparticles are trapped in the mononuclear phagocyte system (MPS) [ 8 , 9 ], of which 85% are Kupffer cells [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Research and Application of Kupffer Cell Thresholds for BSA Nanoparticles

Guo

Tai²,

Liu³

et al. 2023

Molecules

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Over the past decade, the dose of nanoparticles given to solid tumors has remained at a median of 0.7% of the injected dose. Most nanoparticles are trapped in a mononuclear phagocyte system (MPS), of which 85% are Kupffer cells. In our study, threshold doses of bovine serum albumin (BSA) nanoparticles were investigated for the uptake of Kupffer cells in vitro and in vivo. The antitumor effect and safety of albumin-bound paclitaxel (ABP) were improved by using threshold doses of BSA nanoparticles. We found a threshold dose of 20,000 nanoparticles per macrophage uptake in vitro and a saturation dose of 0.3 trillion nanoparticles in tumor-bearing mice. In vivo efficacy and safety evaluations demonstrated that the threshold doses of blank BSA nanoparticles could significantly improve the efficacy and safety of ABP against tumors compared with ABP alone. In this study, the delivery efficiency of ABP was improved by using blank nanoparticles to saturate Kupffer cells, which provided a new approach to studying the Kupffer cell saturation threshold and thus a new scheme for improving the curative effect of ABP.

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Why nanoparticles prefer liver macrophage cell uptake in vivo

Cited by 108 publications

References 152 publications

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

Hemin-incorporating DNA nanozyme enabling catalytic oxygenation and GSH depletion for enhanced photodynamic therapy and synergistic tumor ferroptosis

Polymeric nanocarriers co-encapsulating PET probes and protein therapeutics

Research and Application of Kupffer Cell Thresholds for BSA Nanoparticles

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