Tumor Presence Induces Global Immune Changes and Enhances Nanoparticle Clearance

Abstract

Long-circulating nanoparticles are essential for increasing tumor accumulation to provide therapeutic efficacy. While it is known that tumor presence can alter the immune system, very few studies have explored this impact on nanoparticle circulation. In this report, we demonstrate how the presence of a tumor can change the local and global immune system, which dramatically increases particle clearance. We found that tumor presence significantly increased clearance of PRINT hydrogel nanoparticles from the circulation, resulting in increased accumulation in the liver and spleen, due to an increase in M2-like macrophages. Our findings highlight the need to better understand interactions between immune status and nanoparticle clearance, and suggest that further consideration of immune function is required for success in preclinical and clinical nanoparticle studies.

Lipophilic siRNA targets albumin in situ and promotes bioavailability, tumor penetration, and carrier-free gene silencing

“…enhance understanding of nanoparticle performance in animal models (24)(25)(26)(27), strategies to normalize tumor vasculature (28), systematic investigations into ideal nanoparticle characteristics (24,29), and a focus on smaller (20-30-nm-sized) nanocarriers (24,30,31). Despite the promise of these approaches, the diversity of human cancers necessitates equivalently diverse delivery approaches (23,32) and opportunity for improvement remains, particularly in the area of enhancing uniformity of tumor distribution.…”

A Non-Cytotoxic Resin for Micro-Stereolithography for Cell Cultures of HUVECs

“…On this account, it was vital to identify, which components are potentially released from the 3D-printed parts during application and contribute to the observed cytotoxicity. While TPO-acting as a photo-absorber-was present in all our resins, previous studies on the usage of TPO or its derivative (ethyl 2,4,6-trimethylbenzoylphenylphosphinate) to establish artificial extracellular environments showed that TPO can be safely used and should not influence cell viability, even when used at concentrations as high as 2% w/w compared to concentrations ranging from 0.1% to 0.25% in our resins [26,27]. Uncured resin, as another source for the observed cytotoxicity, should have been consumed in the post-curing process, where 3D-printed objects were exposed to UV-light to achieve complete conversion, and in the sterilization process, which also involved UV-light.…”

Functionalized Nanoparticles Efficiently Enhancing the Targeted Delivery, Tumor Penetration, and Anticancer Activity of 7‐Ethyl‐10‐Hydroxycamptothecin

“…However, the obtained data were controversial and even conflictive, which is understandable as the biological behavior of nanodelivery systems can be affected by a number of parameters such as chemical structure, shape, potential, and size of the nanoparticles . On the other hand, the varied biological models used in different studies may also interfere with the in vitro and in vivo research findings …”