Application of Polymersomes Engineered to Target P32 Protein for Detection of Small Breast Tumors in Mice

Abstract

Triple negative breast cancer (TNBC) is the deadliest form of breast cancer and its successful treatment critically depends on early diagnosis and therapy. The multi-compartment protein p32 is overexpressed and present at cell surfaces in TNBC, specifically in the malignant cells and endothelial cells, and in macrophages localized in hypoxic areas of the tumor. Herein we used polyethylene glycol-polycaprolactone polymersomes that were affinity targeted with the p32-binding tumor penetrating peptide LinTT1 (AKRGARSTA) for imaging of TNBC lesions. A tyrosine residue was added to the peptide to allow for Small triple negative brast tumors can be detected with LinTT1-conjugated polymersomes. Radiolabeled LinTT1-polymersomes were intravenously injected into mice bearing small triple negative breast tumor. LinTT1 peptide binds to p32 protein expressed in the surface of tumor cells and activated macrophage/myeloid cells. LinTT1 is cleaved by urokinase type plasminogen activator (uPA) in tumor, and the processed peptide binds to NRP-1, triggering the penetration of polymersomes into the tumor tissue.

Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology Studies

“…Table 3 compiles syringe retention data of more than 40 types of nanoparticles (core material and functionalization) of medical interest that were radiolabeled and tested in vivo at CIC biomaGUNE at concentrations relevant for medical applications (Conde-Vancells et al, 2008; Locatelli et al, 2012; Pérez-Campaña et al, 2012; Pérez-Campaña et al, 2013; Frigell et al, 2014; Locatelli et al, 2014; Pérez-Campaña, 2014; Ruggiero et al, 2015; Gil, 2016; Ruggiero et al, 2016; Pulagam et al, 2017; Simón-Gracia et al, 2018). The syringes used in these experiments were of the type brand A/3 and brand A/1 which were among those tested at the JRC (see Table 1 ).…”

“…The activity measurements of the full and the empty syringe reported in the present work were performed immediately before and after unloading the syringe. Therefore, even some release of 124 I from polymersomes during several hours (Simón-Gracia et al, 2018), a maximum 10% release of the radiolabel after 72 h from exosomes (Royo et al, 2019) or of < 5% of 68 Ga from biodegradable polymeric nanoparticles in 8 h (Locatelli et al, 2012) will not compromise the results. Moreover, if we assume that the label will be released in ionic form it will be eliminated from the syringe during unloading with the liquid phase.…”

“…Information concerning the synthesis, functionalization, and characterization of the more than 40 types of nanoparticles can be found in the literature cited in Table 3 (Conde-Vancells et al, 2008; Locatelli et al, 2012; Pérez-Campaña et al, 2012; Pérez-Campaña et al, 2013; Frigell et al, 2014; Locatelli et al, 2014; Pérez-Campaña, 2014; Ruggiero et al, 2015; Gil, 2016; Ruggiero et al, 2016; Pulagam et al, 2017; Simón-Gracia et al, 2018; Royo et al, 2019). Here we have to limit ourselves to details which have not yet been published and are complementary to the cited literature.…”

Design of Target Detection and Tracking System for Sports Video

“…(1) On the edge contour, move the horizontal line up one line from the bottom of the image, because the human foot is at the lowest position and symmetrical, so when the horizontal line intersects the contour line for the first time, there must be two. The coordinate of the horizontal line is H1, which is represented by the combination point of the right foot [30]. (2) The joint points of knee, hip, neck and chest were extracted according to the length ratio limitation.…”

Peritoneal Carcinomatosis Targeting with Tumor Homing Peptides

“…In recent years, several other tumor-penetrating peptides have been identified and validated for precision tumor delivery [26,32]. Cyclic CKRGARSTC peptide (codenamed "TT1") was identified by phage biopanning on p32 purified protein [63] and validated as an affinity ligand in different tumor models and administration routes, including in PC models and IP administration [64][65][66]. Both cyclic TT1 and its linear lower-affinity variant, linear TT1 ("LinTT1", sequence: AKRGARSTA), bind to p32 protein (also known as gC1qR or hyaluronic acid binding protein 1, HABP1), an intracellular protein aberrantly expressed on the surface of activated tumor cells, vascular/lymphatic endothelial cells, and macrophages/myeloid cells in hypoxic areas of the tumor [67].…”