Metal-Free Organo-Theranostic Nanosystem with High Nitroxide Stability and Loading for Image-Guided Targeted Tumor Therapy

Abstract

The desire for all-organic-composed nanoparticles (NPs) of considerable biocompatibility to simultaneously diagnose and treat cancer is undeniably interminable. Heretofore, metal-based agents dominate the landscape of available magnetic resonance imaging (MRI) contrast agents and photothermal therapeutic agents, but with associated metal-specific downsides. Here, an all-organic metal-free nanoprobe, whose appreciable biocompatibility is synergistically contributed by its tetra-organo-components, is developed as a viable alternative to metal-based probes for MRI-guided tumor-targeted photothermal therapy (PTT). This rationally entails a glycol chitosan (GC)-linked polypyrrole (PP) nanoscaffold that provides abundant primary and secondary amino groups for amidation with the carboxyl groups in a nitroxide radical (TEMPO) and folic acid (FA), to obtain GC-PP@TEMPO-FA NPs. Advantageously, the appreciably benign GC-PP@TEMPO-FA features high nitroxide loading (r 1 = 1.58 mM–1 s–1) and in vivo nitroxide-reduction resistance, prolonged nitroxide-systemic circulation times, appreciable water dispersibility, potential photodynamic therapeutic and electron paramagnetic resonance imaging capabilities, considerable biocompatibility, and ultimately achieves a 17 h commensurate MRI contrast enhancement. Moreover, its GC component conveys a plethora of PP to tumor sites, where FA-mediated tumor targeting enables substantial NP accumulation with consequential near-complete tumor regression within 16 days in an MRI-guided PTT. The present work therefore promotes the engineering of organic-based metal-free biocompatible NPs in synergism, in furtherance of tumor-targeted image-guided therapy.

Nanocarrier-Based Drug Delivery for Melanoma Therapeutics

“…Nanotechnology also provides strategies for targeted delivery of drugs, genes, and proteins to tumors, thereby reducing their nonspecific accumulation in peripheral tissues [53][54][55]. Currently, the major medical nanomaterials include organic (e.g., liposome, polymeric nanoparticles, and dendrimer) and inorganic (e.g., magnetic nanoparticles, carbon nanoparticles, gold nanoparticles, and silica nanoparticles) nanomaterials [56][57][58], which are used in the diagnosis and treatment of various cancers. Liposomes are amphoteric lipid bilayers with a hydrophilic core and a hydrophobic outer shell [59].…”

Theranostics for MRI‐guided therapy: Recent developments

“…75 More recently, a metal-free nanosystem was designed for MRI-guided tumor-targeted PTT, as shown in Figure 6. 76 This consisted of a glycol chitosan-polypyrrole (GC-PP) scaffold modified with a nitroxide radical (TEMPO) and folic acid (FA). The GC-PP@TEMPO-FA nanoparticles demonstrated a high loading of nitroxide radicals with excellent stability and prolonged circulation time, and the paramagnetic property of the TEMPO protons can reduce water proton longitudinal relaxation times, providing T 1 contrast ability.…”

“…Reproduced with permission. 76 Copyright 2021, American Chemical Society Magnetic targeting has been used to deliver PTT agents and improve photostability, biodistribution, and pharmacokinetics. For example, indocyanine green (ICG) is a clinically approved photothermal agent for fluorescentguided surgery but suffers from poor photostability and low bioavailability.…”

A nitroxides-based macromolecular MRI contrast agent with an extraordinary longitudinal relaxivity for tumor imaging via clinical T1WI SE sequence

“…Nitroxides are unalloyed organic compounds containing single spin electrons [ 13 , 14 ]. Due to their paramagnetism, nitroxides can affect the longitudinal relaxation time (T1) of water protons, thus creating relaxivity, which shares the same mechanism as most commonly used Gd 3+ -based CAs [ 15 – 19 ]. Among nitroxides, 2,2,5,5-tetramethyl-1-pyrrolidinyl- N -oxyl (PROXYL) and 2,2,6,6-tetramethylpiperidinyl-1-oxyl (TEMPO) are mostly studied because of their relatively high stability [ 20 – 23 ].…”