A Novel Biodegradable Nanoplatform for Tumor Microenvironments Responsive Bimodal Magnetic Resonance Imaging and Sonodynamic/Ion Interference Cascade Therapy

Abstract

The unsatisfactory therapeutic effect and long-term adverse effect markedly prevent inorganic nanomaterials from clinical transformation. In light of this, we developed a novel biodegradable theranostic agent (MnCO 3 :Ho 3+ @DOX/Ca 3 (PO 4 ) 2 @BSA, HMCDB) based on the sonosensitizer manganese carbonate (MnCO 3 ) coating with calcium phosphate (Ca 3 (PO 4 ) 2 ) and simultaneously loaded it with the chemotherapeutic drug doxorubicin (DOX). Due to the mild acidity of the tumor microenvironment (TME), the Ca 3 (PO 4 ) 2 shell degraded first, releasing substantial quantities of calcium ions (Ca 2+ ) and DOX. Meanwhile, with the ultrasound (US) irradiation, MnCO 3 produced enough reactive oxygen species (ROS) to cause oxidative stress in the cells, resulting in accumulation of Ca 2+ . Consequently, the cascade effect significantly amplified the therapeutic effect. Importantly, the nanocomposite can be completely degraded and cleared from the body, demonstrating that it was a promising theranostic agent for tumor therapy. Furthermore, the doped holmium ions (Ho 3+ ) and in situ generation of manganese ions (Mn 2+ ) in TME endow the nanoagent with the ability for tumor-specific bimodality T 1 /T 2 -weighted magnetic resonance imaging (MRI). This novel nanoplatform with low toxicity and biodegradability holds great potential for cancer diagnosis and treatment.

PROTAC Nanoplatform with Targeted Degradation of NAD(P)H:Quinone Oxidoreductase 1 to Enhance Reactive Oxygen Species-Mediated Apoptosis

“…To investigate the ability of PNs to tumor tissues, we prepared liposomes with Cy5.5 fluorescent dye as a substitute for DQ and WA. After intravenously injecting free Cy5.5 and Cy5.5-PNs (equivalent Cy5.5 concentration of 3 mg kg −1 ) into A549 tumor-bearing mice via the tail vein, an IVIS Spectrum In Vivo Imaging System (Caliper, Hopkinton, MA) was used to image mice (λ ex/em = 680/704 nm) following anesthesia at various time periods (1,4,8,12, and 24 h). After 24 h, the mice were euthanized at the end of imaging, and their tissues (containing the heart, liver, spleen, lung, kidney, and tumor) were isolated and scanned.…”

“…Tumors are one of the most prevalent and dangerous diseases and are still a huge threat to people worldwide . The treatment of tumors includes surgery, photothermal therapy, radiotherapy, photodynamic therapy, chemotherapy, immunotherapy, stem cell therapy, and hormone therapy. − In the current treatment of tumors, reactive oxygen species (ROS)-induced cell apoptosis is a widely used strategy. − The regulation of intracellular ROS levels is crucial for the determination of homeostasis and cell fate within tumor cells . Sublethal levels of ROS sustain cellular proliferation, transformation, and tumor metastasis, whereas excessive ROS levels directly induce tumor cell apoptosis. − Based on our previous researches, , withaferin A (WA), a promising antitumor active ingredient extracted from Ashwagandha , can provocatively generate ROS to induce cell apoptosis.…”

Composite Nanoplatforms Based on Nanocalcium Peroxide for Cancer Treatment: From Monotherapy to Combination Therapy

“…This approach has been shown to be safe and biocompatible, confirming its potential as an effective treatment option. [85] Yin and colleagues developed a nanoplatform, CaO 2 /Tf/CUR, that co-loaded curcumin (CUR) and Transferrin (Tf) on CaO 2 NPs. [86] The platform was designed to target neoplastic cells through Tf receptor-mediated cytokinesis.…”

Ginsenoside Rk1-Loaded Manganese-Doped Hollow Titania for Enhancing Tumor Sonodynamic Therapy via Upregulation of Intracellular Reactive Oxygen Species

“…Generally, sonosensitizers are classified into organic − and inorganic sonosensitizers. − In contrast to organic sonosensitizers such as methylene blue and porphyrins that fall short in poor bioavailability and rapid body clearance, inorganic sonosensitizers stand out for the stable structure and longtime tumor enrichment. − Titania (TiO 2 ), as a representative inorganic sonosensitizer, holds promising potential in cancer SDT applications. However, the wide band gap of pure TiO 2 (3.2 eV) significantly prevents the generation of ultrasound-induced electrons, which leap from the TiO 2 surface and interact with oxygen to produce singlet oxygen ( 1 O 2 ), and further causes the inadequacy of ROS for SDT .…”