Slippery Nanoparticles as a Diffusion Platform for Mucin Producing Gastrointestinal Tumors

Khalili, Marian; Zhou, Hao; Thadi, Anusha; Daniels, Lynsey; Fan, Zhiyuan; Morano, William F.; Ang, Joanne; Goldstein, Eve; Polyak, Boris; Mapow, Beth; Cheng, Hao; Bowne, Wilbur B.

doi:10.1245/s10434-019-07493-7

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…A recent study has designed a hierarchical PEG structure by optimizing the density and conformation of PEG on the surface of nanoparticles and revealed the protein adsorption kinetics. These “slippery nanoparticles” were used to reduce cell uptake and the mucus penetration process, which was consistent with the analysis in this study that the SNP–mucin interaction was shielded by regulating the PEG density and conformation (Figure (f,g)). Interestingly, the density-dependent fate of carboxyl-modified particles in mucus is unexpected.…”

Section: Discussionsupporting

confidence: 86%

Mucus Penetration of Surface-Engineered Nanoparticles in Various pH Microenvironments

Guo

Chen

et al. 2023

ACS Nano

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The penetration behavior of nanoparticles in mucous depends on physicochemical properties of the nanoparticles and the mucus microenvironment, due to particle–mucin interactions and the presence of the mucin mesh space filtration effect. To date, it is still unclear how the surface properties of nanoparticles influence their mucus penetration behaviors in various physiological and pathophysiological conditions. In this study, we have prepared a comprehensive library of amine-, carboxyl-, and PEG-modified silica nanoparticles (SNPs) with controlled surface ligand densities. Using multiple particle tracking, we have studied the mechanism responsible for the mucus penetration behaviors of these SNPs. It was found that PEG- and amine-modified SNPs exhibited pH-independent immobilization under iso-density conditions, while carboxyl-modified SNPs exhibited enhanced movement only in weakly alkaline mucus. Biophysical characterizations demonstrated that amine- and carboxyl-modified SNPs were trapped in mucus due to electrostatic interactions and hydrogen bonding with mucin. In contrast, high-density PEGylated surface formed a brush conformation that shields particle–mucin interactions. We have further investigated the surface property-dependent mucus penetration behavior using a murine airway distribution model. This study provides insights for designing efficient transmucosal nanocarriers for prevention and treatment of pulmonary diseases.

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Section: Discussionsupporting

confidence: 86%

Mucus Penetration of Surface-Engineered Nanoparticles in Various pH Microenvironments

Guo

Chen

et al. 2023

ACS Nano

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“…Khalili et al 1 present some elegant preclinical research focused on overcoming the steric hinderance of extracellular mucus that impairs drug delivery to mucinous tumors, such as pseudomyxoma peritonei (PMP). They demonstrate homogenous distribution of modified nanoparticles through PMP tumor explants ex vivo and in subcutaneous tumor nodules of mucin-secreting colon cancer cells in vivo.…”

mentioning

confidence: 99%

Defining and Refining the Role for Surgery and Intraperitoneal Chemotherapy in the Treatment of Peritoneal Surface Malignancies

et al. 2019

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The drug release of PLGA-based nanoparticles and their application in treatment of gastrointestinal cancers

Sun,

Chen,

Pei

et al. 2024

Heliyon

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Slippery Nanoparticles as a Diffusion Platform for Mucin Producing Gastrointestinal Tumors

Cited by 3 publications

References 27 publications

Mucus Penetration of Surface-Engineered Nanoparticles in Various pH Microenvironments

Mucus Penetration of Surface-Engineered Nanoparticles in Various pH Microenvironments

Defining and Refining the Role for Surgery and Intraperitoneal Chemotherapy in the Treatment of Peritoneal Surface Malignancies

The drug release of PLGA-based nanoparticles and their application in treatment of gastrointestinal cancers

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