Combined Gadolinium and Boron Neutron Capture Therapies for Eradication of Head-and-Neck Tumor Using Gd10B6 Nanoparticles under MRI/CT Image Guidance.

Eradication of head-and-neck (H&N) tumors is very difficult and challenging because of the characteristic feature of frequent recurrence and the difficulty in killing cancer stem cells. Neutron capture therapy (NCT) is emerging as a noninvasive potential modality for treatments of various types of tumors. Herein, we report that 98.5% 10B-enriched anti-EGFR-Gd10B6 nanoparticles can not only deliver large doses of 158 µg 10B/g tumor tissues as well as 56.8 µg 157Gd/g tumor tissues with a very high tumor-to-blood (T/B) 10B ratio of 4.18, but also exert very effective CT/MRI image-guided combined GdBNCT effects on killing cancer stem cells and eradication of recurrent head-and-neck (H&N) tumors. This leads to a long average half-lifespan of 81 days for H&N tumor-bearing mice, which is a record-making result, and surpasses the best result reported in the literature using combined radiotherapy and T cell-mediated immunotherapy (70 d).

One step synthesis of 10B-enriched 10BPO4 nanoparticles for effective boron neutron capture therapeutic treatment of recurrent head-and-neck tumor.

Recurrent head-and-neck (H&N) cancer is one of the most malignant cancers in the world. Various treatment modalities, such as radiation therapy, chemotherapy, and surgery were adopted to treat H&N cancer, but recurrence of H&N tumor always occurs again, leading to poor prognosis and low 5-year survival rate. Recently, boron neutron capture therapy (BNCT) emerges an alternative modality for curing recurrent tumors. Presently, boron phenylalanine-fructose (BPA-F) and sodium borocaptate (BSH) are the two best BNCT molecular drugs, which, however, have poor therapeutic efficacies and are lack of tumor-targeting ability. In this study, 10B-riched (98.5% 10B) boron phosphate nanoparticles (10BPO4 NPs) of ∼100 nm in size were prepared in a single step using a unique microwave arcing method. The 10B-enriched 10BPO4 NPs were surface-modified with anti-EGFR antibody to endow the targeting ability toward H&N cancer cells. In in-vivo xenograft mice model, a large amount (∼63 µg 10B/g cancer cells) of 10B atoms could be effectively accumulated at the H&N tumor sites using 10BPO4 NPs as BNCT reagents. In in-vitro neutron irradiation experiments, 72% cell deaths were observed from anti-EGFR-10BPO4 NPs-treated H&N cancer cells, which is ∼2.4 folds higher than that (30%) treated with the most effective molecular drug, BPA-F. We demonstrated that upon neutron irradiation, the anti-EGFR-10BPO4 NPs could exert a much higher extent of destruction of H&N tumor, as well as effective suppression of the probability of H&N tumor recurrence, as compared to the most effective molecular drug, BPA-F. The median survival of the BNCT treated mice with anti-EGFR-10BPO4 NPs extends beyond 75 days, which is far better than the mice treated with BPA-F (33 days), blank + NR mice (25), and blank mice (23 days).

Salt-mediated, plasmonic field-field/field-lattice coupling-enhanced NIR-II photodynamic therapy using core-gap-shell gold nanopeanuts.

Plasmonic field-field coupling-induced enhancement of the optical properties of dye molecules in the nanogaps among metal nanoparticle clusters and thin films has attracted significant attention especially in disease-related theranostic applications. However, it is very challenging to synthesize plasmonic core-gap-shell nanostructures with a well-controlled nanogap, uniform shape, and distances to maximize the plasmonic field-field coupling between the core and the shell. Herein, we synthesized Au@gap@AuAg nanopeanut-shaped core-gap-shell nanostructures (Au NPN) and tuned their optical absorption from near-infrared region-I (NIR-I) to near-infrared region-II (NIR-II) by filling their nanogap with a high dielectric NaCl(aq) aqueous solution, which led to a dramatic redshift in the plasmonic absorption band by 320 nm from 660 to 980 nm and a 12.6-fold increase (at 1064 nm) in the extinction coefficient in the NIR region (1000-1300 nm). Upon filling the nanogap with NaCl(aq) aqueous solution, the Au NPN6.5(NaCl) (i.e., ∼6.5 nm nanogap)-mediated NIR-II photodynamic therapy effect was dramatically enhanced, resulting in a much longer average lifespan of >55 days for the mice bearing a murine colon tumor and treated with Au NPN6.5(NaCl) plus 1064 nm light irradiation compared to the mice treated with Au NPN6.5 + 1064 nm light irradiation (without nanogap filled with dielectric NaCl(aq), 40 d) and the doxorubicin-treated group (23 d). This study demonstrates a simple but effective method to tune and maximize the plasmonic field-field coupling between the metal shell and metal core of core-gap-shell nanostructures, the plasmonic field-lattice interactions, and biomedical applications for the treatment of tumors. Overall, our work presents a new way to enhance/maximize the plasmonic field-field and field-lattice coupling, and thus the performance/sensitivities in nanogap-based bioimaging, sensing, and theranostic nanomaterials and devices.

Multifunctional CuO/Cu2O Truncated Nanocubes as Trimodal Image-Guided Near-Infrared-III Photothermal Agents to Combat Multi-Drug-Resistant Lung Carcinoma.

Despite the development of various therapeutic modalities to tackle cancer, multidrug resistance (MDR) and incomplete destruction of deep tissue-buried tumors remain as long-standing challenges responsible for tumor recurrence and low survival rates. In addition to the MDR and deep tissue photoactivation problems, most primary tumors metastasize to the lungs and lymph nodes to form secondary tumors. Therefore, it leaves a great challenge to develop theranostic approaches to combat both MDR and deep tissue photoactivation problems. Herein, we develop a versatile plasmonic CuO/Cu2O truncated nanocube-based theranostic nanomedicine to act as a triple modal near-infrared fluorescence (NIRF) imaging agent in the biological window II (1000-1500 nm)/photoacoustic imaging (PAI)/T1-weighted magnetic resonance (MR) imaging agents, sensitize the formation of singlet oxygen (1O2) to exert nanomaterial-mediated photodynamic therapeutic (NIR-II NmPDT), and absorb long NIR light (i.e., 1550 nm) in the biological window III (1500-1700 nm) to exert nanomaterial-mediated photothermal therapeutic (NIR-III NmPTT) effects for the effective destruction of multi-drug-resistant lung tumors. We found that H69AR lung cancer cells do not create drug resistance toward plasmonic CuO/Cu2O TNCs-based nanomedicines.

Recent Advances of Polyaniline-Based Biomaterials for Phototherapeutic Treatments of Tumors and Bacterial Infections.

Conventional treatments fail to completely eradicate tumor or bacterial infections due to their inherent shortcomings. In recent years, photothermal therapy (PTT) has emerged as an attractive treatment modality that relies on the absorption of photothermal agents (PTAs) at a specific wavelength, thereby transforming the excitation light energy into heat. The advantages of PTT are its high efficacy, specificity, and minimal damage to normal tissues. To this end, various inorganic nanomaterials such as gold nanostructures, carbon nanostructures, and transition metal dichalcogenides have been extensively explored for PTT applications. Subsequently, the focus has shifted to the development of polymeric PTAs, owing to their unique properties such as biodegradability, biocompatibility, non-immunogenicity, and low toxicity when compared to inorganic PTAs. Among various organic PTAs, polyaniline (PANI) is one of the best-known and earliest-reported organic PTAs. Hence, in this review, we cover the recent advances and progress of PANI-based biomaterials for PTT application in tumors and bacterial infections. The future prospects in this exciting area are also addressed.

Engineering Novel Targeted Boron-10-Enriched Theranostic Nanomedicine to Combat against Murine Brain Tumors via MR Imaging-Guided Boron Neutron Capture Therapy.

Glioblastoma multiforme (GBM) is a very common type of "incurable" malignant brain tumor. Although many treatment options are currently available, most of them eventually fail due to its recurrence. Boron neutron capture therapy (BNCT) emerges as an alternative noninvasive therapeutic treatment modality. The major challenge in treating GBMs using BNCT is to achieve selective imaging, targeting, and sufficient accumulation of boron-containing drug at the tumor site so that effective destruction of tumor cells can be achieved without harming the normal brain cells. To tackle this challenge, this study demonstrates for the first time that an unprecedented 10 B-enriched (96% 10 B enrichment) boron nanoparticle nanomedicine (10 BSGRF NPs) surface-modified with a Fluorescein isothiocyanate (FITC)-labeled RGD-K peptide can pass through the brain blood barrier, selectively target at GBM brain tumor sites, and deliver high therapeutic dosage (50.5 µg 10 B g-1 cells) of boron atoms to tumor cells with a good tumor-to-blood boron ratio of 2.8. The 10 BSGRF NPs not only can enhance the contrast of magnetic resonance (MR) imaging to help diagnose the location/size/progress of brain tumor, but also effectively suppress murine brain tumors via MR imaging-guided BNCT, prolonging the half-life of mice from 22 d (untreated group) to 39 d.