Rational Utilization of Black Phosphorus Nanosheets to Enhance Palladium-Mediated Bioorthogonal Catalytic Activity for Activation of Therapeutics.

Pd-catalyzed chemistry has played a significant role in the growing subfield of bioorthogonal catalysis. However, rationally designing Pd nanocatalysts that show outstanding catalytic activity and good biocompatibility poses a great challenge. Herein, we propose an innovative strategy through exploiting black phosphorous nanosheets (BPNSs) to enhance Pd-mediated bioorthogonal catalytic activity. Firstly, the electron-donor properties of BPNSs enable in situ growth of Pd nanoparticles (PdNPs) on it. Meanwhile, due to the superb capability of reducing PdII , BPNSs can act as hard nucleophiles to accelerate the transmetallation in the decaging reaction process. Secondly, the lone pair electrons of BPNSs can firmly anchor PdNPs on their surface via Pd-P bonds. This design endows Pd/BP with the capability to retard tumor growth by activating prodrugs. This work proposes new insights into the design of heterogeneous transition-metal catalysts (TMCs) for bioorthogonal catalysis.

Mitochondria-Targeting Enhanced Phototherapy by Intrinsic Characteristics Engineered "One-for-All" Nanoparticles.

Mitochondria-targeted synergistic therapy, including photothermal (PTT) and photodynamic therapy (PDT), has aroused wide attention due to the high sensitivity to reactive oxygen species (ROS) and heat shock of mitochondria. However, most of the developed nanosystems for the combinatorial functions require the integration of different components, such as photosensitizers and mitochondria-targeted molecules. Consequently, it indispensably requires sophisticated design and complex synthetic procedures. In this work, a well-designed Bi2S3-based nanoneedle, that localizes to mitochondria and produces extra ROS with inherent photothermal effect, was reported by doping of Fe (denoted as FeBS). The engineered intrinsic characteristics certify the capacity of such "one-for-all" nanosystems without additional molecules. The lipophilicity and surface positive charge are demonstrated as crucial factors for specifical mitochondria targeting. Significantly, Fe doping overcomes the disadvantage of the narrow band gap of Bi2S3 to prevent the fast recombination of electron-hole, hence resulting in the generation of ROS for PDT. The "one-for-all" nanoparticles integrate with mitochondria-targeting and synergistic effect of PDT and PTT, thus exhibit enhanced therapeutic effect and inhibit the growth of tumors observably. This strategy may open a new direction in designing the mitochondria-targeted materials and broadening the properties of inorganic semiconductor materials for satisfactory therapeutic outcomes.

A C5 N2 Nanoparticle Based Direct Nucleus Delivery Platform for Synergistic Cancer Therapy.

Intracellular targeting has the same potential as tissue targeting to increase therapy efficacy, especially for drugs that are toxic to DNA. By adjusting intracellular traffic, we developed a novel direct-nucleus-delivery platform based on C5 N2 nanoparticles (NPs). Supramolecular interactions of C5 N2 NPs with the cell membrane enhanced cell uptake; abundant edge amino groups promoted fast and effective rupture of early endosomes; and the appropriate size of the NPs was also crucial for size-dependent nuclear entry. As a proof of concept, the platform was not only suitable for the effective delivery of molecular drugs/dyes (doxorubicin, hydroxycamptothecine, and propidium iodide) and MnO2 nanoparticles to the nucleus, but was also photoresponsive for nucleus-targeting photothermal therapy (PTT) and photodynamic therapy (PDT) to further greatly increase anticancer efficacy. This strategy might open the door to a new generation of nuclear-targeted enhanced anticancer therapy.

Plasmonic titanium nitride nanoparticles for in vivo photoacoustic tomography imaging and photothermal cancer therapy.

Titanium nitride, an alternative plasmonic material to gold with unique physiochemical properties, has been widely used in microelectronics, biomedical devices and food-contact applications. However, its potential application in the area of biomedicine has not been effectively explored. With the spectral match of their plasmon resonance band and the biological transparency window as well as good biocompatibility, titanium nitride nanoparticles (TiN NPs) are promising photoabsorbing agents for photothermal therapy (PTT) and photoacoustic imaging. Nevertheless, the photothermal performance of TiN NPs has not been investigated until now. Here, we presented the investigation of employing TiN NPs as photoabsorbing agents for in vivo photoacoustic tomography (PAT) imaging-guided photothermal cancer therapy. Our experimental results showed that TiN NPs could strongly absorb the NIR light and provided up to 48% photothermal conversion efficiency. After PEGylation, the resultant nanoparticles demonstrated improved physiological stability and extensive blood retention. Following intravenously administration, they could simultaneously enhance the photoacoustic signals of the tumor region and destroy tumors in the tumor-bearing mouse model by taking advantage of the photothermal effect of the TiN NPs. Our findings highlighted the great potential of plasmonic TiN NPs in detection and treatment of cancer.

Targeted polydopamine nanoparticles enable photoacoustic imaging guided chemo-photothermal synergistic therapy of tumor.

Near infrared light responsive nanoparticles can transfer the absorbed NIR optical energy into heat, offering a desirable platform for photoacoustic (PA) imaging guided photothermal therapy (PTT) of tumor. However, a key issue in exploiting this platform is to achieve optimal combination of PA imaging and PTT therapy in single nanoparticle. Here, we demonstrate that the biodegradable polydopamine nanoparticles (PDAs) are excellent PA imaging agent and highly efficient for PTT therapy, thus enabling the optimal combination of PA imaging and PTT therapy in single nanoparticle. Upon modification with arginine-glycine-aspartic-cysteine acid (RGDC) peptide, PDA-RGDC can successfully target tumor site. Moreover, PDA-RGDC can load a chemotherapy drug, doxorubicin (DOX), whose release can be triggered by near-infrared (NIR) light and pH dual-stimuli. The in vitro and in vivo experiments show that this platform can deliver anti-cancer drugs to target cells, release them intracellular upon NIR irradiation, and effectively eliminate tumors through chemo-photothermal synergistic therapeutic effect. Our results offer a way to harness PDA-based theranostic agents to achieve PA imaging-guided cancer therapy. STATEMENT OF SIGNIFICANCE: NIR-light adsorbed nanoparticles combing the advantage of PAI and PTT (TNP-PAI/PTT) are expected to play a significant role in the dawning era of personalized medicine. However, the reported Au-, Ag-, Cu-, Co-, and other metal based, carbon-based TNP-PAI/PTT suffer from complex multicomponent system and poor biocompatibility and biodegradability. To overcome this limitation, biocompatible polydopamine nanoparticles (PDAs), structurally similar to naturally occurring melanin, were designed as both PA imaging contrast agent and a chemo-thermotherapy therapy agent for tumor. RGDC peptide modified PDAs can improve the PA imaging and PTT efficiency and specific targeted deliver doxorubicin (DOX) to perinuclear region of tumor cells. Our finding may help the development of PDA-based nanoplatform for PA imaging-directed synergistic therapy of tumor in clinic.