Injectable magnetic montmorillonite colloidal gel for the postoperative treatment of hepatocellular carcinoma

Abstract

Bioactive materials have been extensively developed for the adjuvant therapy of cancer. However, few materials can meet the requirements for the postoperative resection of hepatocellular carcinoma (HCC) due to massive bleeding and high recurrence. In particular, combination therapy for HCC has been highly recommended in clinical practice, including surgical resection, interventional therapy, ablation therapy and chemotherapy. Herein, an injectable magnetic colloidal gel (MCG) was developed by controllable electrostatic attraction between clinically available magnetic montmorillonites and amphoteric gelatin nanoparticles. The optimized MCG exhibited an effective magnetic heating effect, remarkable rheological properties, and high gel network stability, realizing the synergistic treatment of postoperative HCC by stimuli-responsive drug delivery, hemostasis and magnetic hyperthermia. Furthermore, a minimal invasive MCG-induced interventional magnetic hyperthermia therapy (MHT) under ultrasound guidance was realized on hepatic tumor rabbits, providing an alternative therapeutics to treat the postoperative recurrence. Overall, MCG is a clinically available injectable formulation for adjuvant therapy after HCC surgical resection.

Exploring the Potential of Montmorillonite as an Antiproliferative Nanoagent against MDA-MB-231 and MCF-7 Human Breast Cancer Cells

“…Therefore, the injection of Mt-based anticancer products (e.g., pure Mt, drug-loaded Mt, Mt-based gels loaded with a drug, etc.) into inoperable tumors or tumor resection sites may be a feasible approach for the local or postoperative treatment of MDA-MB-231 breast cancer, as is supported by the promising results of in vivo studies on nanoclay-based anticancer products [21][22][23][24][25].…”

“…Some benefits of local cancer treatment include improving the permeability and retention of therapeutic agents, reducing the administration frequency, reducing the systemic toxicity, and making it possible to treat inoperable tumors or cancers with high locoregional recurrence [49]. Direct injection of nanoclay-based anticancer agents into tumors and/or tumor resection sites is one of the emerging strategies for local cancer treatment [21][22][23][24][25]. Since Mt cytotoxicity is dependent on Mt concentration, protein level, and cell type, Mt may be an ideal candidate for local cancer treatment.…”

“…Recently, clay minerals, such as montmorillonite (Mt), halloysite, laponite, kaolinite and layered double hydroxide, as nanocarriers of imaging/therapeutic agents were successfully injected into the circulation for diagnosis and/or systemic treatment of cancers [13,[15][16][17][18][19][20]. In addition, clay minerals as nanocarriers of genes/drugs were successfully injected into tumors or tumor resection sites for local cancer treatment, thereby increasing the efficacy and reducing the systemic toxicity of the therapeutic agents [21][22][23][24][25]. Mt, a phyllosilicate consisting of nanosheets with ~1 nm thickness and ~30 nm to several microns in diameter, is FDA-approved for oral, transdermal, rectal, and vaginal use and has long been applied in pharmaceutical products as an active/excipient ingredient [26].…”

“…For instance, an injectable intratumoral hydrogel composed of Mt, gemcitabine drug, and biodegradable polymers was prepared for the local treatment of pancreatic tumors [25]. An injectable gel consisting of magnetic Mt, doxorubicin drug, and gelatin was prepared for the postoperative treatment of hepatic tumor resection sites [22]. Intravenous injectable nanocomposites composed of Mt, mitoxantrone drug and FePt nanoparticles were developed to simultaneously image and treat hepatic tumors [15].…”

Dual Responsive Magnetic Drug Delivery Nanomicelles with Tumor Targeting for Enhanced Cancer Chemo/Magnetothermal Synergistic Therapy

“… 13 Magnetic targeting is an emerging tumor therapy technique that involves injecting magnetic nanoparticles into the body and using an external magnetic field to deliver drugs, heat, or other therapeutic substances to the tumor tissue. 14 , 15 The technique can cure tumor tissue long-term and effectively with recurrent magnetic treatment. Magnetic targeting exhibits a magnetothermal effect that generates heat more uniformly than photothermal and photodynamic therapy.…”