Functional Nanoparticles for Tumor Penetration of Therapeutics

Theranostic nanoparticles recently received great interest for uniting unique functions to amplify therapeutic efficacy and reduce side effects. Despite the enhanced permeability and retention (EPR) effect, which amplifies the accumulation of nanoparticles at the site of a tumor, tumor heterogeneity caused by the dense extracellular matrix of growing cancer cells and the interstitial fluid pressure from abnormal angiogenesis in the tumor inhibit drug/particle penetration, leading to inhomogeneous and limited treatments. Therefore, nanoparticles for penetrated delivery should be designed with different strategies to enhance efficacy. Many strategies were developed to overcome the obstacles in cancer therapy, and they can be divided into three main parts: size changeability, ligand functionalization, and modulation of the tumor microenvironment. This review summarizes the results of ameliorated tumor penetration approaches and amplified therapeutic efficacy in nanomedicines. As the references reveal, further study needs to be conducted with comprehensive strategies with broad applicability and potential translational development.

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Effect of Tumor Heterogeneity on Interstitial Pressure and Fluid Flow

Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tissue Engineering; Cerebral Aneurysms; Computational Biofluid Dynamics; Device Design, Human Dynamics, and Rehabilitation; Drug Delivery and Disease Treatment; Engineered Cellular Environments ◽

10.1115/sbc2013-14089 ◽

2013 ◽

Cited By ~ 1

Author(s):

Matthew Pyrz ◽

James Baish

Keyword(s):

Fluid Flow ◽

Solid Tumors ◽

Normal Tissue ◽

Tumor Heterogeneity ◽

Interstitial Fluid ◽

Fluid Pressure ◽

Lymphatic Vessels ◽

Fluid Loss ◽

Interstitial Pressure ◽

Tumor Blood Vessels

Delivery of drugs to solid tumors is often impeded by the elevation of the interstitial fluid pressure at the tumor core and the loss of plasma from the tumor to the surrounding normal tissue. Interstitial pressure in tumors is abnormally high because tumor blood vessels are highly permeable relative to their normal counterparts and tumors lack functional lymphatic vessels that can absorb the excess fluid loss [1]. As a result, there is a net outward flow of plasma-like fluid through the interstitial spaces of the tumor toward the exterior of the tumor where functional lymphatics may be found (Fig. 1).

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Control of interstitial fluid pressure: Role of [beta ]-integrins

Seminars in Nephrology ◽

10.1053/snep.2001.21646 ◽

2001 ◽

Vol 21 (3) ◽

pp. 222-230 ◽

Cited By ~ 42

Author(s):

Rolf K. Reed ◽

Ansgar Berg ◽

Eli-Anne B. Gjerde ◽

Kristofer Rubin

Keyword(s):

Interstitial Fluid ◽

Fluid Pressure ◽

Interstitial Fluid Pressure

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Dynamics of Interstitial Fluid Pressure in Extracellular Matrix Hydrogels in Microfluidic Devices

Journal of Biomechanical Engineering ◽

10.1115/1.4031020 ◽

2015 ◽

Vol 137 (9) ◽

Cited By ~ 5

Author(s):

Joe Tien ◽

Le Li ◽

Ozgur Ozsun ◽

Kamil L. Ekinci

Keyword(s):

Extracellular Matrix ◽

Pressure Distribution ◽

Interstitial Fluid ◽

Scaling Laws ◽

Fluid Pressure ◽

Interstitial Fluid Pressure ◽

External Loading ◽

Interstitial Pressure ◽

Time Resolved ◽

Long Time

In order to understand how interstitial fluid pressure and flow affect cell behavior, many studies use microfluidic approaches to apply externally controlled pressures to the boundary of a cell-containing gel. It is generally assumed that the resulting interstitial pressure distribution quickly reaches a steady-state, but this assumption has not been rigorously tested. Here, we demonstrate experimentally and computationally that the interstitial fluid pressure within an extracellular matrix gel in a microfluidic device can, in some cases, react with a long time delay to external loading. Remarkably, the source of this delay is the slight (∼100 nm in the cases examined here) distension of the walls of the device under pressure. Finite-element models show that the dynamics of interstitial pressure can be described as an instantaneous jump, followed by axial and transverse diffusion, until the steady pressure distribution is reached. The dynamics follow scaling laws that enable estimation of a gel's poroelastic constants from time-resolved measurements of interstitial fluid pressure.

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pH-responsive size-shrinkable mesoporous silica-based nanocarrier for improved tumor penetration and therapeutic efficacy

Nanoscale ◽

10.1039/d1nr07513f ◽

2022 ◽

Author(s):

Yongju He ◽

Xingyu Fan ◽

Xiaozan Wu ◽

Taishun Hu ◽

Fangfang Zhou ◽

...

Keyword(s):

Tumor Microenvironment ◽

Mesoporous Silica ◽

Therapeutic Efficacy ◽

Anticancer Therapy ◽

Major Obstacle ◽

Drug Penetration ◽

Ph Responsive ◽

Tumor Penetration ◽

Promising Strategy

Poor tumor penetration is a major obstacle to nanomedicine for achieving effective anticancer therapy. Tumor microenvironment-induced nanomedicine size shrinkage is a promising strategy to overcome the drug penetration barrier across...

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