Chemo-photodynamic combined gene therapy and dual-modal cancer imaging achieved by pH-responsive alginate/chitosan multilayer-modified magnetic mesoporous silica nanocomposites

Abstract

Multifunctional theranostics have offered some interesting new opportunities for cancer therapy and diagnosis in the last decade. Herein, magnetic mesoporous silica nanoparticles (M-MSNs) were designed and synthesized, then the photosensitizer chlorin e6 (Ce6) and antitumor drug doxorubicin (Dox) were adsorbed onto the M-MSNs. Biocompatible alginate/chitosan polyelectrolyte multilayers (PEM) were assembled on the M-MSNs to achieve a pH-responsive drug delivery system and adsorb P-gp shRNA for reversing the multidrug resistance. The obtained M-MSN(Dox/Ce6)/PEM/P-gp shRNA nanocomposites were characterized using TEM, SEM, X-ray diffraction, BET, FTIR and electrophoresis. The nanocomposites with average diameter of 280 nm exhibited a pH-responsive drug release profile, and more singlet oxygen generation in cancer cells after laser illumination. CCK-8 assay and calcein-AM/PI co-staining showed that the multifunctional nanocomplexes significantly increased cell apoptosis in vitro. With tumor-bearing Balb/c mice employed as the animal model, combined photodynamic therapy and chemotherapy was carried out, also achieving synergistic anti-tumor effects in vivo. The cores of bifunctional FeO-Au nanoparticles in the multifunctional nanocomposites enabled dual-modal MR and CT imaging, which illustrated strong tumor uptake of these nanocomposites after intravenous injection into tumor-bearing mice. This work highlights the great potential of magnetic mesoporous silica nanocomposites as a multifunctional delivery platform, which is promising for imaging-guided cancer combination therapy with high efficacy.

A Magnetofluorescent Carbon Dot Assembly as an Acidic H2O2‐Driven Oxygenerator to Regulate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy

“…Currently, to overcome the tumor hypoxia and enhance the PDT efficiency, three primary approaches have been instigated: (1) the integration of different modal therapies such as photothermal therapy,[8d,10a,11] chemotherapy, radiotherapy, and gene therapy with PDT for a synergistic treatment; (2) the exploration of oxygen carriers such as perfluorocarbon nanodroplets and oxygenated hemoglobin (HbO 2 ) for transporting oxygen into a tumor; and (3) the construction of smart nanoplatforms for the in situ generation of oxygen inside the solid tumors based on the features of the tumor microenvironment such as acidic pH (6.5–6.9) and high‐H 2 O 2 content (0.5 nmol/10 4 cells h −1 ) . Among them, thanks to the acidic H 2 O 2 ‐responsive properties, MnO 2 nanostructures can not only be reduced into Mn(II) by acidic H 2 O 2 as an efficient T 1 contrast agent for magnetic resonance (MR) imaging but also generate an amount of oxygen within the solid tumor for significant enhancement of the PDT efficacy .…”

Targeted and stimuli–responsive mesoporous silica nanoparticles for drug delivery and theranostic use

“…In addition, the molecular probes or the contrast agents useful for magnetic resonance imaging, computed tomography scan, optimal imaging, and radionuclide imaging should be added to these nanoparticles for the characterization of cellular and subcellular processes (Cole & Holland, ). Theranostic nanomedicines with intrinsic optical and photochemical features as well as having the potential to deliver drug have attracted a great interest of cancer researchers (An et al, ; Lee, Lee, Kim, Kim, & Hyeon, ; Yang et al, ). Table elaborates two examples of MPSNPs having theranostic features.…”

Chitosan‐based multifunctional nanomedicines and theranostics for targeted therapy of cancer

“…Chitosan has been used in the combination with MNPs for the targeted delivery of magnetic diagnostic/therapeutic modalities . This strategy was shown to allow a targeted delivery through an external force since the CS‐grafted drug‐loaded MNPs can be concentrated in the desired site where a constant, externally applied magnetic field is used …”

“…These NPs are considered to be superior to the currently commonly used contrast agents such as gadolinium‐based compounds in part due to their lower toxicity and increase in the proton relaxation resulting in lower detection limit . Therefore, SPIONs can be used as theranostic agents, allowing for simultaneous diagnosis and therapy . Lee et al.…”

“…172,173 This strategy was shown to allow a targeted delivery through an external force since the CS-grafted drug-loaded MNPs can be concentrated in the desired site where a constant, externally applied magnetic field is used. 174,175 One of the most effective strategies for the cancer therapy seems to be the noninvasive MRI using SPIONs as the contrast agent. These NPs are considered to be superior to the currently commonly used contrast agents such as gadolinium-based compounds in part due to their lower toxicity and increase in the proton relaxation resulting in lower detection limit.…”