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Black phosphorus nanosheets (BPs) show great potential for various applications including biomedicine, thus their potential side effects and corresponding improvement strategy deserve investigation. Here, in vitro and in vivo biological effects of BPs with and without titanium sulfonate ligand (TiL4 ) modification are investigated. Compared to bare BPs, BPs with TiL4 modification (TiL4 @BPs) can efficiently escape from macrophages uptake, and reduce cytotoxicity and proinflammation. The corresponding mechanisms are also discussed. These findings may not only guide the applications of BPs, but also propose an efficient strategy to further improve the biocompatibility of BPs.

Biodegradable inorganic nanomaterials have opened new perspectives for cancer therapy due to their inherent anticancer activity. Black phosphorus nanosheets (BPs) with their unique bioactivity have recently been identified as promising cancer therapeutic agents but their application is hampered by the difficulty in surface functionalization. Herein, an in situ calcium phosphate (CaP) mineralization strategy is described to enhance the anticancer activity of BPs. By using BPs as the phosphate sources and growth templates, the synthesized CaP‐mineralized BPs (CaBPs) retain the intrinsic properties of BPs and at the same time have high loading capacities for various fluorophores to enable effective bioimaging and tracing. Compared to BPs, CaBPs exhibit enhanced and selective anticancer bioactivity due to the improved pH‐responsive degradation behavior and intracellular Ca2+ overloading in cancer cells. Furthermore, CaBPs specifically target mitochondria and cause structural damage, thus leading to mitochondria‐mediated apoptosis in cancer cells. After intravenous injection, CaBPs target orthotopic breast cancer cells to inhibit tumor growth without giving rise to adverse effects or toxicity. The results demonstrate the great potential of CaBPs as targeted anticancer agents and the CaP mineralization approach provides a versatile surface functionalization strategy for nanotherapeutic agents. [ABSTRACT FROM AUTHOR]

Black phosphorus nanosheets (BPs) are demonstrated to be highly bioactive anti‐cancer agents because of their inherent and selective chemotherapeutic effects. Fast intracellular biodegradation of BPs and acute elevation of phosphate anions were observed from different types of cancer cells due to the stronger intracellular oxidative stress and accelerated energy metabolism, but normal cells are not affected. Selective biodegradation of BPs induced G2/M phase arrest and subsequent apoptosis‐ and autophagy‐mediated cell death in cancer cells but not normal cells. The selectivity was superior to that of the traditional chemotherapeutic agent, doxorubicin (DOX). In vivo assessment confirmed the efficiency of BPs in suppressing tumor growth. This study provides insights into nanostructured bioactive anti‐cancer agents and reveals a new direction for nanomedicine research. Selective chemotherapy: Black phosphorus nanosheets constitute a new type of bioactive anti‐cancer agent. They selectively induce proliferation inhibition, G2/M arrest and apoptotic/autophagic cell death in cancer cells during natural degradation. [ABSTRACT FROM AUTHOR]

Abstract: A biodegradable two‐dimensional (2D) delivery platform based on loading black phosphorus nanosheets (BPs) with Cas9 ribonucleoprotein engineered with three nuclear localization signals (NLSs) at C terminus (Cas9N3) is successfully established. The Cas9N3‐BPs enter cells effectively via membrane penetration and endocytosis pathways, followed by a BPs biodegradation‐associated endosomal escape and cytosolic releases of the loaded Cas9N3 complexes. The Cas9N3‐BPs thus provide efficient genome editing and gene silencing in vitro and in vivo at a relatively low dose as compared with other nanoparticle‐based delivery platforms. This biodegradable 2D delivery platform offers a versatile cytosolic delivery approach for CRISPR/Cas9 ribonucleoprotein and other bioactive macromolecules for biomedical applications. [ABSTRACT FROM AUTHOR]

Ultrasmall black phosphorous nanosheets (BPs) can trigger systemic inflammations. In their Communication on page 14488 ff., X.‐F. Yu, G. Jiang, et al. report a method to reduce this side effect by surface modification of bare BPs with titanium sulfate (TiL4@BPs). The girl represents a potential candidate exposed to bare BPs through various routes during a wide application of this material. The effect of the bare BPs is shown by red shading. The BPs are less harmful after conversion to TiL4@BPs. [ABSTRACT FROM AUTHOR]

X-ray induced photodynamic therapy (X-ray-PDT) is a promising approach for synergistic cancer radiotherapy and development of suitable radiosensitizers is highly desired. In this paper, we propose black phosphorus/Bi 2 O 3 (BP/Bi 2 O 3 ) heterostructures as efficient and biocompatible radiosensitizers for synergistic cancer radiotherapy. The heterostructures are synthesized by growth of ultrasmall Bi 2 O 3 nanoparticles onto BP nanosheets. The Bi 2 O 3 decoration inhibits the rapid degradation of BP nanosheets by occupation of the defect sites, and the synergistic effects of BP and Bi 2 O 3 enable 1 O 2 overproduction under X-ray irradiation. This X-ray-PDT effect of the BP/Bi 2 O 3 nanosheets enhances the radiotherapy activity towards cancer cells by inducing cell apoptosis and cycle arrest. In vivo treatment of melanoma conducted on a clinical radiotherapeutic instrument demonstrates that the BP/Bi 2 O 3 sensitized radiotherapy inhibits tumor growth efficiently. Furthermore, the BP/Bi 2 O 3 nanosheets composed of biological friendly P, O, and Bi elements shows good biocompatibility in vitro and in vivo . This radiosensitizer thus has immense clinical potential for cancer therapy, and our findings reveal a general strategy to fabricate stable BP-based heterostructures for different applications. [ABSTRACT FROM AUTHOR]

Black phosphorus (BP) discovered a century ago constitutes a new class of two-dimensional (2D) materials and is intensively studied as a 2D semiconductor. The high carrier mobility and tunable and moderate direct bandgap of BP deliver great promise in electronic and optoelectronic applications and the unique intrinsic anisotropy arising from the puckered structure produces extraordinary electronic, optical, transport, thermal, and mechanical properties that can be exploited in the design of new devices. Furthermore, the biodegradability and biocompatibility of BP bode well for biomedical applications. In this review, we discuss recent advances pertaining to the synthesis, modification, properties, and applications of BP and address some of the challenges and opportunities of BP research. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is the most aggressive malignant tumor with difficulty in early diagnosis, very short survival time in advanced stage, and lack of effective treatment options. In this work, a novel combination chemotherapy strategy based on bioactive black phosphorus (BP) and gemcitabine (GEM) is developed for efficient treatment of pancreatic cancer. The combined cell cycle blockage in G2/M phase induced by BP and G0/G1 phase by GEM results in synergistic killing of pancreatic cancer cells with the combination index (CI) < 1. The iRGD modified zein nanoparticles co-loaded with BP quantum dots (BPQDs) and GEM are designed and prepared as a targeted nanoplatform (BP-GEM@NPs). After intravenous injection, the in vivo distribution and pharmacokinetics results demonstrate that BP-GEM@NPs shows excellent tumor targeting capability and significantly prolonged blood circulation time. The targeted co-delivery of BPQDs and GEM induces much more pancreatic tumor cell apoptosis and synergistically inhibits tumor growth in both subcutaneous xenograft and orthotopic models. Meanwhile, BP-GEM@NPs exhibit good biocompatibility without bring adverse effects. This work indicates the great potential of BP-GEM@NPs as a combination chemotherapy for pancreatic cancer and provides insights into development of biomedicine by exploring the intrinsic bioactivities of nanomaterials. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • BPQDs encapsulated cRGD-liposomes are fabricated. • BPQDs are on-demand released after targeted delivery to tumor sites. • The expression of P-gp is strongly inhibited under NIR irradiation. • Synergistic photothermal-chemotherapy is achieved by only BPQDs towards resistant tumor ablation. Treatment of drug-resistant tumors is a great challenge and nanoplatforms combining advanced therapeutic functions have many advantages in offering efficient treatment. However, the reported fabrication of nanoplatforms for multi-modal therapy of tumors is complicated or even uncontrollable since several kinds of therapeutic agents need to be assembled into the nanoparticles. Herein, black phosphorus (BP)-based photosensitive nanocapsules (BP-PNCs) are designed as a highly efficient nanoplatform against resistant tumors by integrating the inherent photothermal and chemotherapeutic effects of BP. BP-PNCs are synthesized by encapsulating BP quantum dots (BPQDs) into the core of liposome and DSPE-PEG 2000 -cRGD is incorporated into the liposomal bilayers to render BP-PNCs with high cellular uptake and effective in vivo tumor targeting capability after intravenous injection. In vitro and in vivo assessments demonstrate that BP-PNCs in conjunction with near-infrared (NIR) light irradiation lead to complete obliteration of resistant A549R tumors. The excellent anti-cancer efficacy stems from the synergistic therapeutic effects arising from the NIR light induced BP photothermal effects, which result in hyperthermia ablation and triggering the liposome phase transition to release internal BPQDs to perform BP chemotherapeutic effects. The expression inhibition of P-gp by hyperthermia further improves the chemotherapeutic efficiency. BP-PNCs with a simple structure and intrinsic multi-functionalities have great potential in treating resistant tumors and our results provide insights into the design of multifunctional nanoplatforms for biomedicine. [ABSTRACT FROM AUTHOR]

Circulating tumor DNA (ctDNA) identification is one of the most meaningful approaches towards early cancer diagnosis. However, effective and practical methods for analyzing this emerging class of biomarkers are still lacking. In this work, a biosensor based on nitrophenyl functionalized black phosphorus nanosheets (NP-BPs) is fabricated for sensitive and selective detection of ctDNA. In this work, a nitrophenyl functionalized black phosphorus nanosheets (NP-BPs) biosensor is fabricated for sensitive and selective detection of ctDNA. Due to the successful nitrophenyl functionalization, the NP-BPs biosensor shows higher quenching efficiency and stronger affinity towards single-stranded DNA (ssDNA), as compared with double-stranded DNA (dsDNA). Therefore, the NP-BPs biosensor exhibits 5.4-fold fluorescence enhancement when dye-labelled ssDNA probe forms dsDNA in the presence of its specific ctDNA target. This biosensor exhibits a detection limit of 50 fM and a wide linear detection range of 50 fM-80 pM, provides reliable readout in a short time (15 min). Moreover, the NP-BPs-based biosensor could be applied to discriminate single nucleotide polymorphisms in clinical serum samples. It is envisioned that the NP-BPs-based sensing platform has great potentials in early cancer diagnosis and monitoring cancer progression. • Two-dimensional biosensor has been fabricated to detect DNA in human serum samples. • NP-BPs biosensor shows high selectivity and excellent sensitivity towards ctDNA. • The proposed approach provide keys to the clinical potential boasting rapid, and accurate detection of ctDNA. [ABSTRACT FROM AUTHOR]