Zhenglin Li

Multifunctional Bismuth Selenide Nanocomposites for Antitumor Thermo-Chemotherapy and Imaging

To integrate real-time monitoring and therapeutic functions into a single nanoagent, we have designed and synthesized a drug-delivery platform based on a polydopamine(PDA)/human serum albumin (HSA)/doxorubicin (DOX) coated bismuth selenide (Bi2Se3) nanoparticle (NP). The resultant product exhibits high stability and biocompatibility both in vitro and in vivo. In addition to the excellent capability for both X-ray computed tomography (CT) and infrared thermal imaging, the NPs possess strong near-infrared (NIR) absorbance, and high capability and stability of photothermal conversion for efficient photothermal therapy (PTT) applications. Furthermore, a bimodal on-demand pH/photothermal-sensitive drug release has been achieved, resulting in a significant chemotherapeutic effect. Most importantly, the tumor-growth inhibition ratio achieved from thermo-chemotherapy of the Bi2Se3@PDA/DOX/HSA NPs was 92.6%, in comparison to the chemotherapy (27.8%) or PTT (73.6%) alone, showing a superior synergistic therapeutic effect. In addition, there is no noticeable toxicity induced by the NPs in vivo. This multifunctional platform is, therefore, promising for effective, safe and precise antitumor treatment and may stimulate interest in further exploration of drug loading on Bi2Se3 and other competent PTT agents combined with in situ imaging for biomedical applications.

Multimodal Imaging-Guided Antitumor Photothermal Therapy and Drug Delivery Using Bismuth Selenide Spherical Sponge

Elaborately designed biocompatible nanoplatforms simultaneously having diverse therapeutic and imaging functions are highly desired for biomedical applications. Herein, a Bi2Se3 nanoagent with a special morphology as a nanoscale spherical sponge (NSS) has been fabricated and investigated in vitro and in vivo. The highly porous NSS exhibits strong, steady, and broad-band absorbance in the near-infrared range as well as high efficiency and stability of photothermal conversion, resulting in high antitumor efficacy for photothermal therapy (PTT). Together with a high X-ray attenuation coefficient (218% that of the clinically used iopromide), the NSS shows excellent performance on triple-modal high-contrast imaging, including X-ray-computed tomography, multispectral optoacoustic tomography, and infrared thermal imaging. Furthermore, the high surface area and porous structure impart the NSS a competent drug loading capability as high as 600% of that on Bi2Se3 nanoplates, showing a bimodal pH/photothermal sensitive drug release and pronounced synergetic effects of thermo-chemotherapy with a tumor inhibition ratio even higher than that of PTT alone (∼94.4% vs ∼66.0%). Meanwhile, the NSS is highly biocompatible with rather low in vitro/in vivo toxicity and high stability, at variance with easily oxidized Bi2Se3 nanoagents reported previously. Such biocompatible single-component theranostic nanoagents produced by a facile synthesis and highly integrated multimodal imaging and multiple therapeutic functions may have substantial potentials for clinical antitumor applications. This highly porous nanostructure with a large fraction of void space may allow versatile use of the NSS, for example, in catalysis, gas sensing, and energy storage, in addition to accommodating drugs and other biomolecules.

Ultrahigh-sensitive optical temperature sensing based on ferroelectric Pr3+-doped (K0.5Na0.5)NbO3

Optical temperature sensing based on the variation of the fluorescence intensity ratio of rare-earth materials has become appealing due to the multiple superiorities over the electrical temperature sensing. However, confined by the largest energy separation of two thermally linked levels of rare-earth ions, the highest sensitivity of such temperature sensing is essentially smaller than 2878/T2, as reported previously from diverse systems. In this work, we demonstrate that ultrahigh-sensitive temperature sensing can be achieved from Pr3+-doped (K0.5Na0.5)NbO3 based on the intensity ratio of the 1D2-3H4 emission to the 3P0-3H4 emission. The ratio can be increased as high as 18-fold when temperature rises from room temperature to 456 K, nicely fitting a thermally linked-levels-like equation and showing an ultrahigh sensitivity of 7997/T2. The striking change of the ratio is attributed to the interaction between the two emission levels and the intervalence charge transfer state. This work may have provided a ...

Multifunctional Bi@PPy-PEG Core–Shell Nanohybrids for Dual-Modal Imaging and Photothermal Therapy

High-performance theranostic nanoagents, which integrate multimodal imaging and photothermal therapy for clinical anticancer treatment, are highly desired. Herein, we report the synthesis and bioapplication of a multifunctional theranostic nanoagent based on polyethylene glycol (PEG)-modified polypyrrole (PPy)-coated bismuth (Bi) nanohybrids (referred to as Bi@PPy-PEG NHs) for X-ray computed tomography/photoacoustic (CT/PA) dual-modal imaging and photothermal therapy (PTT). The obtained Bi@PPy-PEG NHs have a distinct core-shell structure with the metallic Bi nanoparticle as the inner core and the PPy-PEG layer as the shell. The Bi@PPy-PEG NHs show excellent physiological stability and compatibility, without noticeable cytotoxicity. Importantly, the NHs exhibit strong NIR absorbance and remarkable photothermal conversion capability and conversion stability, with the photothermal conversion efficiency as high as ∼46.3%. Thanks to the strong PTT effect, highly effective photothermal ablation on cancer cells has been achieved both in vitro and in vivo. Furthermore, a high-contrast in vitro and in vivo CT/PA dual-modal imaging has been realized, showing great potential to provide comprehensive diagnosis information for antitumor treatment. In particular, the CT enhancement efficiency of the NHs is of ∼14.4 HU mM-1, which is ∼3.7-fold that of clinically used iohexol. Therefore, our work highlights the potential of using such core-shell Bi@PPy-PEG NHs as a versatile theranostic nanoplatform for cancer imaging and therapy.

Epigenetic silencing of ASPP1 confers 5-FU resistance in clear cell renal cell carcinoma by preventing p53 activation: ASPP1 inhibits ccRCC

Inactivation of p53 has been shown to correlate with drug resistance in tumors. However, in clear cell renal cell carcinoma (ccRCC), p53 is rarely mutated, yet the tumors remain highly insensitive to the conventional chemotherapeutic drugs. The underlying mechanisms responsible for the non‐genetic p53 inactivation remain obscure. Here, we report, for the first time, that Apoptosis Stimulating of P53 Protein 1 (ASPP1) was remarkably downregulated at both mRNA (about 3.9‐fold) and protein (about 4.9‐fold) levels in ccRCC human specimens in comparison with the paired normal controls. In addition, lower ASPP1 was closely related to the higher grade of tumors and shorter life expectancy of ccRCC patients, both with p < 0.001. We also find that CpG island hypermethylation at promoter region contributed to the suppression of ASPP1 expression in ccRCC that contained relatively low levels of ASPP1. Further functional studies demonstrated that forced expression ASPP1 not only significantly inhibited the growth rate of ccRCC, but also promoted sensitivity of ccRCC to the conventional chemotherapeutic drug 5‐fluorouracil (5‐FU)‐induced apoptosis. Moreover, ASPP1 expression was accompanied with the apoptosis‐prone alterations of p53 targets expression and p53 target PIG3 luciferase reporter activation. In contrast, ASPP1 knockdown promoted cell growth and prevent 5‐FU‐induced p53 activation and apoptosis. In conclusion, our results suggest that ASPP1 silencing is one of dominate mechanisms in inhibiting wild type p53 in ccRCC. ASPP1, therefore, may be potentially used as a promising biomarker for prognosis and therapeutic intervention in ccRCC.

Polyethylene glycol-modified cobalt sulfide nanosheets for high-performance photothermal conversion and photoacoustic/magnetic resonance imaging

Theranostic nanoagents that integrate the diagnoses and therapies within a single nanomaterial are compelling in their use for highly precise and efficient antitumor treatments. Herein, polyethylene glycol (PEG)-modified cobalt sulfide nanosheets (CoS-PEG NSs) are synthesized and unitized as a powerful theranostic nanoagent for efficient photothermal conversion and multimodal imaging for the first time. We demonstrate that the obtained CoS-PEG NSs show excellent compatibility and stability in water and various physiological solutions, and can be effectively internalized by cells, but exhibit a low cytotoxicity. The CoS-PEG NSs exhibit an efficient photothermal conversion capacity, benefited from the strong near-infrared (NIR) absorption, high photothermal conversion efficiency (∼33.0%), and excellent photothermal stability. Importantly, the highly effective photothermal killing effect on cancer cells after exposure to CoS-PEG NSs plus laser irradiation has been confirmed by both the standard Cell Counting Kit-8 and live-dead cell staining assays, revealing a concentration-dependent photothermal therapeutic effect. Moreover, utilizing the strong NIR absorbance together with the T2-MR contrast ability of the CoS-PEG NSs, a high-contrast triple-modal imaging, i.e., photoacoustic (PA), infrared thermal (IRT), and magnetic resonance (MR) imaging, can be achieved, suggesting a great potential for multimodal imaging to provide comprehensive cancer diagnosis. Our work introduces the first bioapplication of the CoS-PEG nanomaterial as a potential theranostic nanoplatform and may promote further rational design of CoS-based nanostructures for precise/efficient cancer diagnosis and therapy.

Mesoporous silica-coated bismuth nanohybrids as a new platform for photoacoustic/computed tomography imaging and synergistic chemophotothermal therapy

AIM Polyethylene glycol modified mesoporous silica-coated bismuth nanohybrids (Bi@mSiO2-PEG) are fabricated for chemothermotherapy and multimodal imaging. MATERIALS & METHODS The Bi@mSiO2-PEG are synthesized by coating mesoporous SiO2 onto metallic Bi cores, followed by PEG modification. Their cytotoxicity, photothermal effect, drug loading, antitumor effect and imaging abilities are evaluated. RESULTS The nanohybrids show good biocompatibility, strong near-infrared absorbance, high photothermal conversion efficiency (∼36.6%), prominent infrared thermal imaging and photothermal killing efficacy on cancer cells. Utilizing the nanohybrids as potent drug carriers, a synergistic antitumor effect through chemothermotherapy is realized. Thanks to the superhigh x-ray attenuation coefficient and strong photothermal ability, high-contrast photoacoustic and x-ray computed tomography imaging are achieved. CONCLUSION These results reveal great potentials of the Bi@mSiO2-PEG for precise and efficient anticancer treatments.

Dual-Stimuli Responsive Bismuth Nanoraspberries for Multimodal Imaging and Combined Cancer Therapy

Development of stimuli-responsive theranostics is of great importance for precise cancer diagnosis and treatment. Herein, bovine serum albumin (BSA) modified bismuth nanoraspberries (Bi-BSA NRs) are developed as cancer theranostic agents for multimodal imaging and chemo-photothermal combination therapy. The Bi-BSA NRs are synthesized in aqueous phase via a facile reduction method using Bi2O3 nanospheres as the sacrificial template. The morphology, biocompatibility, photothermal effect, drug loading/releasing abilities, chemotherapy effect, synergistic chemo-photothermal therapy efficacy, and multimodal imaging capacities of Bi-BSA NRs have been investigated. The results show that the NRs possess multiple unique features including (i) raspberry-like morphology with high specific surface area (∼52.24 m2·g-1) and large cavity (total pore volume ∼0.30 cm3·g-1), promising high drug loading capacity (∼69 wt %); (ii) dual-stimuli responsive drug release, triggered by acidic pH and NIR laser irradiation; (iii) infrared thermal (IRT), photoacoustic (PA) and X-ray computed tomography (CT) trimodality imaging with the CT contrast enhanced efficiency as high as ∼66.7 HU·mL·mg-1; (iv) 100% tumor elimination through the combination chemo-photothermal therapy. Our work highlights the great potentials of Bi-BSA NRs as a versatile theranostics for multimodal imaging and combination therapy.

Highly efficient photothermal sterilization of water mediated by Prussian blue nanocages

Developing green and efficient techniques for water sterilization is of great importance to public health. In this work, highly efficient photothermal water sterilization mediated by Prussian blue nanocages (PBNs) has been realized. The PBNs are synthesized via a facile hydrothermal method, which can act as high-performance photothermal agents owing to their strong and broad optical absorption covering the entire ultraviolet, visible and near-infrared (NIR) regions as well as their competent photothermal conversion capability. Using Escherichia coli as the bacterial model, a high photothermal antibacterial efficacy (∼100%) is achieved upon NIR irradiation as short as 5 min even at a low dosage (100 μg mL−1). Moreover, the results of the sterilization of polluted drinking water with all kinds of mixed bacteria show that the PBNs can eliminate almost all bacteria upon 10 min of NIR irradiation. Importantly, the photothermal sterilization effect of the PBNs upon mild solar irradiation (0.1 W cm−2) is also demonstrated, showing a killing rate of ∼99% upon 10 min of irradiation. Our work has highlighted the great potential of photothermal sterilization employing solar light for practical water treatments.

Phase‐Transition Induced Conversion into a Photothermal Material: Quasi‐Metallic WO2.9 Nanorods for Solar Water Evaporation and Anticancer Photothermal Therapy

Phase transition from WO3 to sub-stoichiometric WO2.9 by a facile method has varied the typical semiconductor to be quasi-metallic with a narrowed band gap and a shifted Femi energy to the conduction band, while maintaining a high crystallinity. The resultant WO2.9 nanorods possess a high total absorption capacity (ca. 90.6 %) over the whole solar spectrum as well as significant photothermal conversion capability, affording a conversion efficiency as high as around 86.9 % and a water evaporation efficiency of about 81 % upon solar light irradiation. Meanwhile, the promising potential of the nanorods for anticancer photothermal therapy have been also demonstrated, with a high photothermal conversion efficiency (ca. 44.9 %) upon single wavelength near-infrared irradiation and a high tumor inhibition rate (ca. 98.5 %). This study may have opened up a feasible route to produce high-performance photothermal materials from well-developed oxides.