LDL mediated delivery of Paclitaxel and MRI imaging probes for personalized medicine applications

Abstract

Background The combination of imaging and therapeutic agents in the same smart nanoparticle is a promising option to perform a minimally invasive imaging guided therapy. In this study, Low density lipoproteins (LDL), one of the most attractive biodegradable and biocompatible nanoparticles, were used for the simultaneous delivery of Paclitaxel (PTX), a hydrophobic antitumour drug and an amphiphilic contrast agent, Gd-AAZTA-C17, in B16-F10 melanoma cell line. These cells overexpress LDL receptors, as assessed by flow cytometry analysis. Results PTX and Gd-AAZTA-C17 loaded LDLs (LDL-PTX-Gd) have been prepared, characterized and their stability was assessed under 72 h incubation at 37 °C and compared to LDL loaded with Gd-AAZTA-C17 (LDL-Gd) and LDL-PTX. The cytotoxic effect of LDL-PTX-Gd was evaluated by MTT assay. The anti-tumour drug loaded into LDLs showed a significantly higher toxicity on B16-F10 cells with respect to the commercially available formulation Paclitaxel kabi (PTX Kabi) used in clinical applications. Tumour cells uptake was initially assessed by ICP-MS and MRI on B16-F10 cell line. By the analysis of the image signal intensity, it was possible to extrapolate the amount of internalized PTX indirectly by the decrease of relaxation times caused by Gd, proportional to its concentration. Finally, the treatment with PTX loaded LDL on B16-F10 tumour bearing mice resulted in a marked reduction of tumour growth compared to the administration of PTX Kabi alone. Conclusions LDLs are selectively taken-up by tumour cells and can be successfully exploited for the selective delivery of Paclitaxel and imaging agents. For the first time the anon invasive “in vivo” determination of the amount of PTX accumulated in the tumour was possible, thanks to the use of theranostic agents of natural origin. Graphic abstract

Boosting Checkpoint Immunotherapy with Biomimetic Nanodrug Delivery Systems

“…used LDL to deliver both paclitaxel (PTX) and the amphiphilic contrast agent Gd‐AAZTA‐C17 ( Figure A). [ 81 ] Magnetic resonance imaging monitoring showed the best tumor inhibition in LDL‐PTX‐treated mice (Figure 4B). This study made it possible for the accumulated concentration of PTX to be detected precisely in tumors via a noninvasive method in vivo.…”

“…Reproduced with permission. [ 81 ] Copyright 2021, The Authors. Schematic illustration of C) preparation process and D) principle of self‐assembly nanoreactor to break down through cascade reaction.…”

Low-density lipoprotein: a versatile nanoscale platform for targeted delivery

“…Several LDL-based MRI probes have been reported in recent years after the optimization of the targeting system. 92–96…”

“…Several LDL-based MRI probes have been reported in recent years aer the optimization of the targeting system. [92][93][94][95][96] 4.1.3 Loading uorescent dyes. Near-infrared uorescence (NIRF) imaging has been proven to be a non-invasive and effective real-time imaging method.…”