Intelligent Nanocomposites with Intrinsic Blood–Brain‐Barrier Crossing Ability Designed for Highly Specific MR Imaging and Sonodynamic Therapy of Glioblastoma

Abstract

The blood–brain barrier (BBB) is the most important obstacle to improving the clinical outcomes of diagnosis and therapy of glioblastoma. Thus, the development of a novel nanoplatform that can efficiently traverse the BBB and achieve both precise diagnosis and therapy is of great importance. Herein, an intelligent nanoplatform based on holo‐transferrin (holo‐Tf) with in situ growth of MnO2 nanocrystals is constructed via a reformative mild biomineralization process. Furthermore, protoporphyrin (ppIX), acting as a sonosensitizer, is then conjugated into holo‐Tf to obtain MnO2@Tf‐ppIX nanoparticles (TMP). Because of the functional inheritance of holo‐Tf during fabrication, TMP can effectively traverse the BBB for highly specific magnetic resonance (MR) imaging of orthotopic glioblastoma. Clear suppression of tumor growth in a C6 tumor xenograft model is achieved via sonodynamic therapy. Importantly, the experiments also indicate that the TMP nanoplatform has satisfactory biocompatibility and biosafety, which favors potential clinical translation.

Mesenchymal Stem Cells Functionalized Sonodynamic Treatment for Improving Therapeutic Efficacy and Compliance of Orthotopic Oral Cancer

“…To advance its application potential, many feasible strategies have been developed, and especially, the combination of sonosensitizers and nanocarriers has emerged as a promising solution, including liposomes, [15] polymers, [16] metal nanoparticles (NPs), [17] nanoceramic, [18] as well as other organic and inorganic NPs, [19] which may significantly improve payload stability, targeting, and therapeutic efficacy, while reducing toxicity. [20] Despite many these advantages, the therapeutic outcomes of SDT are often limited by poor tumor accumulation, [21] fast clearance by reticuloendothelial tissues, [22] nanocarrier toxicity, and especially the presence of biological barriers in tumors, [23] such as hypoxic core, [24] low extracellular pH, [25] high interstitial fluid pressure, and poor tumor penetration. [13] Therefore, there is a need of developing new strategy to overcome therapeutic hurdles and increase SDT efficacy for oral cancer.…”

Hemoglobin-mediated biomimetic synthesis of paramagnetic O2-evolving theranostic nanoprobes for MR imaging-guided enhanced photodynamic therapy of tumor

“…Besides BSA, we also explored a human endogenous protein, glutathione S-transferase (GST), to synthesize a bimodal probe for cancer computerized tomography (CT)/magnetic resonance (MR) imaging 23 . Our previous work and other published studies have shown advantages of proteins for the biomimetic synthesis of nanostructures, particularly for facile integration of multiple functionalities 20 , 24 - 27 .…”

Recent Advances in Nanomaterial‐Assisted Combinational Sonodynamic Cancer Therapy

“…In another example, an intelligent nanoplatform based on holo-transferrin (holo-Tf) with in situ growth of MnO 2 nanocrystals and modified with the PpIX sonosensitizer was constructed for high-efficiency SDT on malignant glioblastoma (Figure 15A,B). [108] In the tumor microenvironment, both the generation of O 2 and reduction of the GSH level derived from MnO 2 nanocrystals greatly increased the efficiency of SDT. More recently, Liu and co-workers developed a multifunctional stimuli-responsive nanomedicine for the depletion of GSH, Ca 2+ induced mitochondria damage, and enhancement of SDT to cause cancer cell death by tripling the amplification of tumor oxidative stress (Figure 16A).…”