Extracellular matrix physical properties govern the diffusion of nanoparticles in tumor microenvironment

Abstract

Nanoparticles (NPs) are confronted with limited and disappointing delivery efficiency in tumors clinically. The tumor extracellular matrix (ECM), whose physical traits have recently been recognized as new hallmarks of cancer, forms a main steric obstacle for NP diffusion, yet the role of tumor ECM physical traits in NP diffusion remains largely unexplored. Here, we characterized the physical properties of clinical gastric tumor samples and observed limited distribution of NPs in decellularized tumor tissues. We also performed molecular dynamics simulations and in vitro hydrogel experiments through single-particle tracking to investigate the diffusion mechanism of NPs and understand the influence of tumor ECM physical properties on NP diffusion both individually and collectively. Furthermore, we developed an estimation matrix model with evaluation scores of NP diffusion efficiency through comprehensive analyses of the data. Thus, beyond finding that loose and soft ECM with aligned structure contribute to efficient diffusion, we now have a systemic model to predict NP diffusion efficiency based on ECM physical traits and provide critical guidance for personalized tumor diagnosis and treatment.

Real-time imaging of nanobubble ultrasound contrast agent flow, extravasation, and diffusion through an extracellular matrix using a microfluidic model

“…This has been shown in other studies on nanoparticle delivery efficiency through an ECM. 72 Due to this microfluidic device's tunable properties, adaptations of this setup could be used to study barriers to extravasation and diffusion such as stiffer matrices ( e.g. , different materials for the matrix or cross-linking) or a permeabilizable endothelium.…”

Generation of multicellular tumor spheroids via 3D cell culture utilizing a hydrogel comprising chitosan and allylthiourea

“…Furthermore, the appearance of a new peak corresponding to the stretching of CQN between 1610-1620 cm À1 provided evidence of the formation of a hydrogel through dynamic imine bond formation. 46 The structure of chitosan was confirmed with 13 C CP-TOSS solid-state NMR, with the chemical shift values at 30 ppm (-CH 3 ), 64 ppm C2 (-CH-NH 2 ), 66 ppm C6 (-CH 2 OH), 82 ppm C5, C3 (-CHOH,-CH-O-), 89 ppm C4 (-CH-O-), 111 ppm C1 (-CH-O-), and 181 ppm (-COCH 3 ), respectively. 47 The 13 C peaks of allylthiourea are obtained at 46 ppm C9 (-CH 2 ), 117 ppm C10 (QCH-), 135 ppm C11(QCH 2 ) and 179 ppm C8 (CQS).…”

“…[10][11][12] The effectiveness of nanoparticle drugs in personalized tumor diagnosis and therapy is influenced by the physical characteristics of the extracellular matrix (ECM), as revealed by in vitro hydrogel experiments and molecular dynamics simulations employing single particle tracking. 13 In addition to the previously mentioned traits, tumor microenvironments can also display diversity in their physical attributes. These include variations in stiffness, density, and composition in different parts of the tumor.…”

Promising Nanomedicines of Shikonin for Cancer Therapy

“…In addition, decorating nanomedicines with tumor penetrating peptides, camouflaging with cell membrane and modulating tumor extracellular matrix can improve the tumor targeting and penetration ability. [149][150][151] (2) Drug resistance. Drug resistance is one of the leading causes of cancer chemotherapy failure.…”