As a rising star, black phosphorous (BP) is a two-dimensional material in the form of a single layer or several layers. Due to its extraordinary physical properties, this single-element two-dimensional material has attracted widespread attention in the fields of optoelectronic devices, energy, and biomedicine. The following is a summary of some important research on black phosphorous materials in the biomedical direction in the past year for everyone to exchange and learn.

AFM review: research progress of black phosphorus in biomedicine and biosensing

Black phosphorus (BP) nanomaterials include BP nanosheets, BP quantum dots and BP nanoparticles. Nano BP has excellent surface activity, adjustable band gap, high carrier mobility, high biocompatibility and good biodegradability. Therefore, nano BP has advantages in the fields of biomedicine and biosensing Very high application value. Guo Shaojun‘s team from Peking University reviewed the synthesis and functionalization of nano-BP and its research progress in biomedicine and biosensing in recent years.

The author first introduced various methods for preparing nano-BP, such as mechanical method, liquid-phase ultrasonic exfoliation method, electrochemical exfoliation method, etc., and on this basis, proposed two methods to improve the stability of nano-BP; BP‘s biological imaging (fluorescence imaging, thermal imaging, photoacoustic imaging), disease treatment (optical therapy, photo/chemical/immune synergistic therapy), and its application as nanocarriers and nanomedicine; then it introduces nano BP in biosensing The applications of BP include electrochemical biosensing, fluorescent biosensing and chemiluminescence biosensing. Finally, the application prospects of nano-BP in the biological field are also prospected.

Xiaoxiao Ge, Shaojun Guo. et al. Recent Advances on Black Phosphorus for Biomedicine and Biosensing. Advanced Functional Materials. 2019

https://doi.org/10.1002/adfm.201900318

Zhang Xudong & Meilin ACS Nano: Personalized photothermal vaccine derived from surgically resected tumor for cancer immunotherapy

Individualized tumor vaccines can induce effective and long-lasting anti-tumor responses, so they have great potential and value in cancer immunotherapy. However, because tumor antigens tend to have low immunogenicity and weak immune response, there are still many obstacles to the development of personalized tumor vaccines that need to be resolved urgently. The surgically removed tumors often contain tumor antigens for the patient, which also provides a good source of personalized tumor vaccines. The research group of Professor Mei Lin of School of Pharmacy of Sun Yat-sen University (Shenzhen) and the team of Xudong Zhang of Sun Yat-sen University School of Medicine used surgically removed tumors to prepare personalized photothermal vaccines, and combined with PD-1 checkpoint blocking antibodies can effectively prevent tumor recurrence and metastasis.

The experiment prepared black phosphorus quantum dot nanovesicles (BPQD-CCNVs) coated with the cell membrane of the surgically resected tumor, and packed them into a thermosensitive hydrogel containing GM-CSF and LPS. After subcutaneous injection of Gel-BPQD-CCNVs, it was found that it can continuously release GM-CSF to effectively recruit dendritic cells (DCs) to capture tumor antigens. Near-infrared light irradiation and LPS will stimulate the activation of DCs, allowing DCs to enter lymph nodes and express antigens to CD8+ T cells. In addition, through the combined application with PD-1 antibody, the vaccine also significantly enhances the ability of tumor-specific CD8+ T cells to clear surgical residual tumors and lung metastases. In summary, this work provides a very good strategy for the clinical development of personalized cancer vaccines.

Ye X Y, Liang X, et al. Surgical Tumor-Derived Personalized Photothermal Vaccine Formulation for Cancer Immunotherapy. ACS Nano, 2019.

https://pubs.acs.org.ccindex.cn/doi/10.1021/acsnano.8b07371

Nature Commun.: Extracellular vesicles embedded with black phosphorus molecules are used for molecular recognition guided biomineralization

Extracellular vesicles (EVs) participate in processes such as the regulation of cell physiological activities and the reconstruction of the extracellular environment. Stromal vesicles (MVs) are a type of EV released by bone-related functional cells, which participate in the regulation of cell mineralization. Dr. Wang Jie, Professor Yuan Quan and Professor Zhang Yufeng from Wuhan University have jointly reported a biomimetic MVs (Apt-bioinspired MVs) embedded with black phosphorus (BP) and functionalized with cell-specific aptamers for biomineralization.

The aptamer can direct MVs to act directly on target cells, while BP can increase the concentration of inorganic phosphate to promote cell biomineralization. At the same time, the photothermal effect of Apt-bioinspired MVs can also promote the process of biomineralization by stimulating the up-regulated expression of heat shock proteins and alkaline phosphatase. The experimental results show that Apt-bioinspired MVs have excellent bone regeneration performance. This work also provides a new method for designing bionic materials for studying the mechanism of biological processes and medical engineering.

Yingqian Wang, Jie Wang, Yufeng Zhang, Quan Yuan. et al. Bioinspired extracellular vesicles embedded with black phosphorus for molecular recognition-guided biomineralization. Nature Communications. 2019

https://doi.org/10.1038/s41467-019-10761-5

Nano Lett.: Multimodal nanomaterials based on black phosphorus are used for targeted combination therapy of cancer metastasis

It is still a big challenge to develop precise targeted multifunctional nanomedicine to achieve effective breast cancer tumor treatment (especially metastatic tumor). The Liu Sijin team from the Environmental Ecology Research Center of the Chinese Academy of Sciences and the Yu Xuefeng team from the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences successfully designed and synthesized a multifunctional black phosphorus (BP)-based nanomaterial BP/DTX@PLGA to solve this problem.

In the experiment, BP quantum dots (BPQDs) were loaded into PLGA and coupled with the chemotherapy drug docetaxel (DTX). The results of the in vivo distribution show that BP/DTX@PLGA has good targeting properties for primary tumors and lung metastases. In addition, BP/DTX@PLGA also has excellent chemical-photothermal combined therapy performance, which can effectively treat tumors under near-infrared light irradiation. The photothermal effect will also accelerate the release of DTX from the nanocomposite, and synergistically lead to programmed cell death, thereby eliminating lung metastases. Both in vivo and in vitro experimental results confirmed that BP/DTX@PLGA has good biocompatibility. Therefore, this research provides a promising BP-based multimodal nanomedicine for inhibiting tumors and their metastasis.

Shunhao Wang, Xue-Feng Yu, Sijin Liu. et al. Black Phosphorus-Based Multimodal Nanoagent: Showing Targeted Combinatory Therapeutics against Cancer Metastasis. Nano Letters. 2019

https://pubs.acs.org/doi/10.1021/acs.nanolett.9b02127

AFM: NIR/ROS responsive BPQVs as immune adjuvant carriers for specific tumor photodynamic therapy

Two-dimensional black phosphorus (BP) nanosheets and BP quantum dots, as the two main types of BP materials, have a wide range of applications in the field of biomedicine. However, few studies report that BP nanocarriers that respond to stimuli can meet the needs of nanomedicine. Here, the research team of Prof. Huanghao Yang and Prof. Jibin Song of Fuzhou University prepared a near-infrared/reactive oxygen (NIR/ROS) sensitive BPQD through self-assembly of polyethylene glycol and reactive oxygen-sensitive polypropylene sulfide (PPS) grafted amphiphilic BPQD. Vesicles (BPNVs).

BPNVs show enhanced light absorption in the near-infrared region, and BPNVs show higher loading efficiency of immune adjuvant CPG oligonucleotides (CPG ODNs) in the cavity. At the same time, BPNVs can generate a high concentration of ROS, which triggers the conversion of hydrophobic PPS into hydrophilic polymers, leading to the decomposition of vesicles into BPNDs. Due to the simultaneous release of BPQDs, which can penetrate tumors deeply, and CpG, which can enhance immunotherapy, BPNV can show the effect of combining photodynamic therapy with immunotherapy. Experimental results show that, in addition to blocking the growth and metastasis of distant tumors, BPNVs-CpG can also achieve effective photodynamic immunotherapy in the body.

Zhi Li, Jibin Song, Huanghao Yang, et al. NIR/ROS-Responsive Black Phosphorus QD Vesicles as Immunoadjuvant Carrier for Specific Cancer Photodynamic Immunotherapy. Adv. Funct. Mater., 2019.

https://doi.org/10.1002/adfm.201905758

AM: Low toxicity and fast-acting black phosphorus assisted depression therapy

Professor Wang Xiaolei of Nanchang University and Zhang Wenhua project combined to form a drug delivery system based on black phosphorus (BP) nanosheets containing therapeutic drugs (fluoxetine, Flu). According to subsequent behavioral, biochemical and electrophysiological analysis, BP-Flu can significantly reduce the treatment time of depression after irradiation with near-infrared light (808 nm). At the same time, the inherent biological toxicity of Flu has also been alleviated.

Jin, L., Hu, P., Wang, Y., Wu, L., et al. Fast-Acting Black-Phosphorus-Assisted Depression Therapy with Low Toxicity. Adv. Mater. 2019, 1906050.

https://doi.org/10.1002/adma.201906050