Gadolinium(III)-Chelated Silica Nanospheres Integrating Chemotherapy and Photothermal Therapy for Cancer Treatment and Magnetic Resonance Imaging

Abstract

The combination of therapy and diagnosis has been emerging as a promising strategy for cancer treatment. To realize chemotherapy, photothermal therapy, and magnetic resonance imaging (MRI) in one system, we have synthesized a new magnetic nanoparticle (Gd@SiO2-DOX/ICG-PDC) integrating doxorubicin (DOX), indocyanine green (ICG), and gadolinium(III)-chelated silica nanospheres (Gd@SiO2) with a poly(diallyldimethylammonium chloride) (PDC) coating. PDC coating serves as a polymer layer to protect from quick release of drugs from the nanocarriers and increase cellular uptake. The DOX release from Gd@SiO2-DOX/ICG-PDC depends on pH and temperature. The process will be accelerated in the acidic condition than in a neutral pH 7.4. Meanwhile, upon laser irradiation, the photothermal effects promote DOX release and improve the therapeutic efficacy compared to either DOX-loaded Gd@SiO2 or ICG-loaded Gd@SiO2. Moreover, MRI results show that the Gd@SiO2-PDC nanoparticles are safe T1-type MRI contrast agents for imaging. The Gd@SiO2-PDC nanoparticles loaded with DOX and ICG can thus act as a promising theranostic platform for multimodal cancer treatment.

Nanoformulations for combination or cascade anticancer therapy

“…With the ability of photosensitizer, ICG allows the combination of PTT with PDT. ICG has been encapsulated into, or coated onto inorganic particles, polymeric micelles for multiple purposes [232]. Metals such as gold (Au) or silver (Ag) can also generate heat through the so-called “surface plasmon” phenomenon.…”

Advanced Functional Nanomaterials for Theranostics

“…Due to toxicity of the free metal, Gd-based MRI contrast agents are commonly chelated with acyclic or macrocyclic chelating ligands (Figure 6). [111–113] Gd can be incorporated into other materials like silica nanoparticles [114, 115] , liposomes [116] , hydrogels [117] , dendrimers [118, 119] or can be directly linked with biomolecules. [120–123] …”

Magnetic Resonance Imaging and Spectroscopy in Cancer Theranostic Imaging

“…27 Photothermal agents convert light energy into heat, causing a rise of local temperature that consequently kills the cells in the area. Cao et al ., developed a new magnetic nanoparticle that combines, within one system, chemotherapy, photothermal therapy and MRI for detection.…”

“…The particle combined gadolinium-chelated silica nanospheres, DOX, and ICG in a poly diallyldimethylammonium chloride coating (PDC). 27 This coating was used to avoid quick release of the drug from the particle. FDA-approved ICG absorbs NIR light (700-1000 nm) to generate heat and damage cells.…”

“…In vitro , an accelerated release of DOX was demonstrated under acidic conditions, accompanied by a photothermal effect induced by laser irradiation that not only increased the release of DOX but also improved the therapeutic efficacy. 27 Future in vivo studies with this nanoparticle are required to confirm the promising potential of this strategy.…”