Nanomedicines Targeting Glioma Stem Cells.

Glioblastoma (GBM), classified as a grade IV glioma, is a rapidly growing, aggressive, and most commonly occurring tumor of the central nervous system. Despite the therapeutic advances, it carries an ominous prognosis, with a median survival of 14.6 months after diagnosis. Accumulating evidence suggests that cancer stem cells in GBM, termed glioma stem cells (GSCs), play a crucial role in tumor propagation, treatment resistance, and tumor recurrence. GSCs, possessing the capacity for self-renewal and multilineage differentiation, are responsible for tumor growth and heterogeneity, leading to primary obstacles to current cancer therapy. In this respect, increasing efforts have been devoted to the development of anti-GSC strategies based on targeting GSC surface markers, blockage of essential signaling pathways of GSCs, and manipulating the tumor microenvironment (GSC niches). In this review, we will discuss the research knowledge regarding GSC-based therapy and the underlying mechanisms for the treatment of GBM. Given the rapid progression in nanotechnology, innovative nanomedicines developed for GSC targeting will also be highlighted from the perspective of rationale, advantages, and limitations. The goal of this review is to provide broader understanding and key considerations toward the future direction of GSC-based nanotheranostics to fight against GBM.

Photothermal/NO combination therapy from plasmonic hybrid nanotherapeutics against breast cancer.

In this study, a plasmon-semiconductor nanotheranostic system comprising Au nanostars/graphene quantum dots (AuS/QD) hybrid nanoparticles loaded with BNN6 and surface modified with PEG-pyrene was developed for the photo-triggered hyperthermia effect and NO production as the dual modality treatment against orthotopic triple-negative breast cancer. The structure and morphology of the hybrid nanodevice was characterized and the NIR-II induced thermal response and NO production was determined. The hybrid nanodevice has shown enhanced plasmonic energy transfer from localized surface plasmonic resonance of Au nanostars to QD semiconductor that activates the BNN6 species loaded on QD surfaces, leading to the effective NO production and the gas therapy in addition to the photothermal response. The increased accumulation of the NIR-II-responsive hybrid nanotheranostic in tumor via the enhanced permeation and retention effects was confirmed by both in vivo fluorescence and photoacoustic imaging. The prominent therapeutic efficacy of the photothermal/NO combination therapy from the BNN6-loaded AuS@QD nanodevice with the NIR-II laser irradiation at 1064 nm against 4T1 breast cancer was observed both in vitro and in vivo. The NO therapy for the cancer treatment was evidenced with the increased cellular nitrosative and oxidative stress, nitration of tyrosine residues of mitochondrial proteins, vessel eradication and cell apoptosis. The efficacy of the photothermal treatment was corroborated directly by severe tissue thermal ablation and tumor growth inhibition. The NIR-II triggered thermal/NO combination therapy along with the photoacoustic imaging-guided therapeutic accumulation in tumor shows prominent effect to fully inhibit tumor growth and validates the promising strategy developed in this study.

New combination treatment from ROS-Induced sensitized radiotherapy with nanophototherapeutics to fully eradicate orthotopic breast cancer and inhibit metastasis.

Radiotherapy (RT) is one of the most commonly employed approaches in the treatment of malignant tumors and is often combined with radiosensitizers to enhance the therapeutic efficacy for clinical use. For developing a smart therapeutic strategy leveraging local tissue response to photo-mediated reactions and the combination of multiple treatment modalities involving ROS-induced sensitization of RT, a novel nanophototherapeutic system has been developed. The nanotherapeutics prepared from the assembly of poly (thiodiethylene malonate) (PSDEM) and PEG-PSDEM-PEG and loaded with suberoylanilide hydroxamic acid (SAHA) employed as the RT sensitizer and indocyanine green (ICG) as the photothermal/photodynamic agent, demonstrated the capability of undergoing structural change and releasing therapeutic payloads in response to near-infrared irradiation and X-ray radiotherapy. With highly localized and controllable reactions within the tumor site, the reactive oxygen species (ROS)-triggered SAHA unloading and the hyperthermia-induced vascular permeability of oxygen led to a significant sensitization of the target tissue in RT, which, in turn, led to the promotion of therapeutic effect in conjunction with photodynamic/photothermal therapies (PDT/PTT). In vitro studies demonstrated the damage in intracellular DNA double strands and the inhibition of cell proliferation in 4T1 breast cancer cells treated with ROS-induced sensitized RT. A substantial reduction in cell viability was also observed owing to the effects of the combination of photo-mediated treatments with sensitized RT compared to the effects of RT administration alone. Complete eradication of the primary tumor and the inhibition of lung metastasis was observed in five of six orthotopic 4T1 breast cancer-bearing mice subjected to combined PDT/PTT in nanophototherapeutics with ROS-induced sensitized RT at a low dosage (6 Gy), leading to the prominent survival fraction of ca. 83% over 60 days.

Combo-targeted nanoassemblies as a chemotherapy delivery system against peritoneal carcinomatosis colorectal cancer.

Peritoneal carcinomatosis colorectal cancer (pcCRC) is one of the most challenging cases in clinical treatment due to its aggressive characteristics and diagnostic limitations, impeding the therapeutic efficacy of chemotherapy. In this study, a poly(lactic-co-glycolic acid) nanoparticle (NP)-based drug delivery system capable of encapsulating the chemodrug SN38 and enhancing drug accumulation in metastatic tumors was developed for the treatment of pcCRC. The SN38-loaded NPs with a diameter of ca. 160 nm were decorated with N-acetyl histidine-modified d-α-tocopheryl polyethylene glycol succinate (TPGS) and folate-TPGS on their surfaces for enhancing drug accumulation through surface charge conversion in a mildly acidic tumor microenvironment and further allowing the NPs to selectively target the folate receptor-overexpressed colon cancer cells. This hierarchically targeted drug delivery strategy improved not only the highly enhanced cellular uptake of drug-loaded NPs, but also the prominent anticancer effect against CT26 cancer cells in vitro. In vivo studies demonstrated the sound tumor inhibition of the SN38-loaded NPs in terms of large reductions in both tumor size and nodule number and prolongation of the survival time of pcCRC-bearing mice, indicating their high therapeutic potential for the practical treatment of pcCRC.