A Nanoarchitectonic Approach Enables Triple Modal Synergistic Therapies To Enhance Antitumor Effects

Abstract

Improvement of antitumor effects relies on the development of biocompatible nanomaterials and combination of various therapies to produce synergistic effects and avoid resistance. In this work, we developed GBD-Fe, a nanoformulation that effectively integrated chemotherapy (CT), chemodynamic therapy (CDT), and photothermal therapy (PTT). GBD-Fe used gold nanorods as photothermal agents and encapsulated doxorubicin to amplify Fe3+-guided CDT effects by producing H2O2 and reducing the intracellular glutathione levels. In vitro and in vivo experiments were conducted to demonstrate the enhanced accumulation and antitumor effects of this tripronged therapy under magnetic resonance imaging (MRI) guidance. This tripronged approach of CT/CDT/PTT effectively induced tumor cytotoxicity and inhibited tumor growth in tumor-bearing mice and therefore represents a promising strategy to effectively treat tumors.

Application of MOF-based nanotherapeutics in light-mediated cancer diagnosis and therapy

“…CDT, a new tumor nano-catalytic therapy, not only has the advantage of high selectivity and low toxicity compared to PTT and PDT, but also overcomes the disadvantages of PDT which requires external energy for activation when treating deep-seated tumors [129][130][131]. The basic principle of CDT is to use nanotechnology to deliver Fenton or Fenton-like reaction catalysts into tumor tissues, catalyzing the over-expression of H 2 O 2 in tumor cells to produce •OH with strong oxidizing power, causing irreversible oxidative damage to molecules such as liposomes, DNA and proteins in tumor cells, thereby inducing apoptosis and killing tumor cells [132].…”

Manganese-based hollow nanoplatforms for MR imaging-guided cancer therapies

“…The strong surface plasmon resonance (SPR) endows noble metal nanoparticles with prominent optical and photothermal performances, including a high absorption cross-section and superior photothermal conversion efficiency in the NIR biowindow, resulting in extensive application prospects in bioimaging and PTT [ 110 – 112 ]. Based on hollow Au/Ag alloy nanoparticles, Wu et al [ 113 ] fabricated a versatile nanoplatform (Au/Ag-MnO 2 -PEG/Ce6, denoted as AAM-Ce6) with MnO 2 and PEG functionalized as well as Ce6 loaded.…”

Extremely Small Iron Oxide Nanoparticles with pH-Dependent Solubility Transition as T1/T2 Switchable Contrast Agents for MRI

“…Smart polymers that respond to the external stimuli such as pH, redox potential, and enzymes have attracted intense interest in biological applications. − In particular, various pH-responsive polymers have been employed to construct stimulus-responsive nanoplatforms for tumor therapy and imaging. − Among them, polymers with sulfadimethoxine (SDM) groups show a very sharp transition range and remarkably pH-dependent solubility resulting from the ionization of the functional groups in the acid tumor microenvironment (TME), providing a reasonable tactic to design stimulus-responsive CAs. − In addition, a special attention has been paid to the host–guest adamantane/β-CD (Ad/β-CD) complexation in the design of nanostructured materials, due to the strong association constant on account of the great fitness of Ad into β-CD cavity. − In the present work, we designed and prepared polysulfadimethoxine (PSDM)-modified ESIONPs based on the Ad/β-CD complexation as a pH-responsive T 1 /T 2 switchable contrast agent to selectively activate the T 2 MRI signal at the tumor region. Polyethylene glycol (PEG) terminally modified with adamantane (Ad-PEG-NH 2 ) was introduced on the surface of ESIONPs to obtain adamantane-modified ESIONPs (ESIONPs-PEG-Ad).…”