A tumor microenvironment responsive nanosystem for chemodynamic/chemical synergistic theranostics of colorectal cancer

Abstract

Rationale: The synergism of new modalities alongside chemodynamic therapy into common chemotherapy has shown promising potential in clinical applications. This paper reports a tumor microenvironment-responsive nanosystem for chemodynamic/chemical synergistic therapy and magnetic resonance imaging (MRI). Methods: The biodegradable nanosystem is synthesized using a surface-modified chain transfer agent for surface-initiated living radical polymerization of the chemotherapeutic drug. Results: In this nanosystem, named CAMNSN@PSN38, the cycling time and solubility of the chemotherapeutic drug are improved. The nanoparticles delivered to tumor tissues gradually release the chemotherapeutic drug and Mn 2+ through glutathione (GSH)-triggered biodegradation in the tumor microenvironment. SN38, the released chemotherapeutic drug, not only shows excellent chemical therapy effects but also improves the generation of H 2 O 2 . Furthermore, with the Fenton-like agent Mn 2+ , the generation of reactive oxygen species (ROS) is improved markedly. Finally, CAMNSN@PSN38 shows excellent inhibition of tumor growth in three colorectal cancer tumor models, with an improved accumulation of ROS and controlled release of SN38. Conclusions: The CAMNSN@PSN38-mediated chemodynamic/chemical synergistic therapy provides a promising paradigm for the treatment and MRI-guided therapy of colorectal cancer.

Novel Strategy for Optimized Nanocatalytic Tumor Therapy: From an Updated View

“…As such, the in-depth studies of the molecular mechanism of NCT combating tumor cells should also be highlighted, which would promote the development of NCT on pharmacological research, targeted therapy, and further clinical application. 3) Third, the process of Catalytic reaction Nanozyme Fe, Cu, Mn, Ce, MOF-based nanocomposites [11] Surface modification [24] Morphological (2D) nanozyme [26] SACs [29] TME modulating Co-loaded catalysts to promote sequential catalytic reactions [32b,34] Self-amplified H 2 O 2 level [35,36] Improving the GSH/pH condition [37,40] Construction of multifunctional nanosystems Synergistic therapy NCTþchemotherapy [13] NCTþstimuli-responsive therapy [45][46][47][48] NCT þ PDT/ PTT [44] NCTþgene-editing therapy [50] NCTþimmumotherapy [53,57] Targeted therapy / Vehicle mediated [41] Surface ligand mediated [43] Theranostic applications / Fluorescence imaging-guided NCT [59] PA-guided NCT [61] Multimodal imaging-monitored NCT [60] a)…”

“…[ 10 ] Since the initial application of Fe 3 O 4 NPs for NCT in 2016, the investigation and progress of NCT could be summarized in following steps in recent years: 1) exploration of a variety of biocompatible high‐performance nanocatalysts for NCT, such as transition metal ions (Co 2+ , Cu 2+ , and Mn 2+ ) [ 11 ] and metal–organic frameworks (MOFs) [ 12 ] which share parallel catalytic properties of Fe 3 O 4 and 2) modulating TME conditions to maximize the catalytic reaction and generate elevated ROS for the improvement of NCT effects. [ 13 ] 3) At current stage, besides the investigations on the above two aspects, increasing studies have focused on improving the therapeutic efficiency of NCT by formulating multifunctional nanozyme‐based systems to satisfy the demand for versatile applications, including targeted delivery of catalytic nanosystems [ 14 ] and synergistic therapy combining latest immune, [ 15 ] gene editing, [ 16 ] and molecular medicine. [ 17 ] Moreover, accurate theranostic nanoplatforms were successfully constructed to achieve real‐time detection of the antitumor effect of NCT [ 18 ] ( Scheme ).…”

Colorectal cancer therapy mediated by nanomedicines

“…Moreover, the release of SN38 increased from 13% to 54% after adding 10 mM GSH for 48 h, and the release of Mn 2+ increased from 28% to 70%. 38 In addition, GSH can also break the phenolic ester bond in SN38 monomers, which is another mechanism to accelerate the release of SN38. 62…”

Hemoglobin Nanocrystals for Drugs Free, Synergistic Theranostics of Colon Tumor

“…In the presence of H 2 O 2 , Fe 2+ is known to be released and oxidized to Fe 3+ via the Fenton reaction that also produces hydroxyl radicals (•OH), which can rapidly oxidize the surrounding biomolecules and destruct tumors in the process of chemodynamic therapy (CDT). [ 20,21 ] Given the high‐level H 2 O 2 in TME, [ 22 ] hemoglobin can serve as a natural Fenton agent for selective tumor treatment. [ 23 ] At the same time, the Fe 3+ produced in Fenton reaction can, in turn, react with hydrogen sulfide (H 2 S) producing iron sulfide, [ 24,25 ] which has been demonstrated to act as magnetic resonance imaging (MRI) contrast and photothermal agents.…”