The entry of nanoparticles into solid tumours

c-Src controls stability of sprouting blood vessels in the developing retina independently of cell-cell adhesion through focal adhesion assembly

“…Although albumin transport across the endothelium requires Cav1 and caveolae, animals lacking Cav1 display increased albumin leakage in the retinal vasculature (Gu et al, 2014). Additionally, recent studies have shown no role for Cav1 and caveolae in transport across the endothelium in tumors (Sindhwani et al, 2020). Conclusively discerning the effects of c-Src deletion on endothelial transcytosis and the blood-retinal barrier cannot be achieved using confocal microscopy; instead, electron microscopy must be employed.…”

Organ-restricted vascular delivery of nanoparticles for lung cancer therapy

“…We also show that the ORVD technique promotes their extravasation from the deranged tumor vasculature into the core of solid tumors possibly via the recently demonstrated transcytosis pathway. [16] Encouragingly, we observed specific cellular uptake of nanoparticles within the core of solid lung tumors while nanoparticles were retained within the capillaries in regions with healthy tissue. This observation is fully in line with the recent work showing preferential activation of transcytotic transport of particles across the tumor vasculature.…”

“…Additionally, recent evidence suggests that previous reports may have overestimated the contribution of the EPR to directing nanoparticles to tumors and that additional active cellular processes, such as transcytosis, also promote extravasation of nanoparticles into tumors. [16] Many of these experiments have demonstrated proof-of-concept nanoparticle delivery in immunocompromised animals thereby underestimating deposition to immunological active off-target organs upon systemic administration, which remains a major challenge.…”

“…[15] However, these approaches are infrequent due to high levels of pulmonary toxicity resulting from chemotherapeutics accumulating not only in tumors but also in healthy lung tissue. [14] Nanotherapy is particularly well suited for overcoming pulmonary toxicity associated with healthy tissue since with the help of the EPR effect and the recently described transcytotic pathway upregulated in endothelial cells lining the tumor vasculature [16] , nanoparticles could be successfully and selectively delivered to tumorous regions. Here, we provide proof-of-concept evidence for effective delivery of both active and passive targeting nanoparticles with pHresponsiveness into the interior of solid, dense lung tumors using a novel organ-restricted vascular delivery (ORVD) strategy.…”

Engineering Intelligent Nanosystems for Enhanced Medical Imaging

“…[19] However, a recent study suggests that the mechanism by which nanoparticles are accumulated in solid tumors is strongly driven by active transepithelial transport, rather than by passive entry through interendothelial gaps. [20] To further increase accumulation at the target site, nanoparticles can be functionalized with targeting moieties with affinity to specific epitopes of the tissue, a strategy referred to as active targeting. [21] Such moieties may include antibodies, [22][23][24] aptamers, [25][26][27] ligands, [28][29][30] or a combination of those, [31][32][33][34] with high affinity for epitopes that are exclusively (or to a larger extent) present in the target tissue.…”