Abstract
Abstract As one of the prospective two-dimensional nanomaterials, black phosphorus (BP), which has excellent physical and chemical properties, has witnessed quick development in theranostic applications. The more recent advances in combining BP nanosheet (NS) with nanoparticles exhibit new opportunities to develop multifunctional nanocomposites. However, more effort should be devoted to elucidate the nanomaterial-cell interaction mechanism before the bio-applications of BP-nanoparticle hybrids. Herein, the intracellular behaviors of BP-gold nanoparticles (BP-Au NSs) are first investigated using the surface-enhanced Raman scattering (SERS) technique. The presence of Au nanoparticles on the surface of a BP sheet allows nanohybrids with excellent SERS activity to enhance the intrinsic Raman signals of cellular components located around the NSs. Data from an endocytosis inhibitor blocking assay reveal that the nanohybrids are mainly taken up by macropinocytosis and caveolae-dependent endocytosis, which are energy-dependent processes. Associated with colocalization experiments, nanohybrids are found to internalize into lysosomes and the endoplasmic reticulum. Moreover, the SERS difference spectrum is extracted after Raman-fluorescence colocalization statistical analysis to distinguish the molecular structural differences in the biochemical components of the two organelles. These findings supply a definite cellular mechanistic understanding of the nano-biointeractions of nanocomposites in cancer cells, which may be of great importance to the biomedical applications of nanotechnology in the future.
Highlights
Black phosphorus (BP), a metal-free layered semiconductor that possesses predominant physicochemical characteristics [1,2,3], has been extensively applied in the biomedical field, such as biosensors, therapeutics, diagnostics, bioactive scaffolds and medical imaging [4,5,6,7,8,9,10]
Single- or few-layered black phosphorus (BP) NSs were synthesized by a modified mechanical exfoliation method from BP crystal powders in organic solvent [30,31,32]
The transmission electron microscopic (TEM) image shows that the surface of BP NSs is coated with a great deal of globular Au nanosphere whose average size is about 30 nm (Figure 1B)
Summary
Black phosphorus (BP), a metal-free layered semiconductor that possesses predominant physicochemical characteristics [1,2,3], has been extensively applied in the biomedical field, such as biosensors, therapeutics, diagnostics, bioactive scaffolds and medical imaging [4,5,6,7,8,9,10]. As a two-dimensional inorganic nanomaterial, BP possesses a large surface area that enables it to serve as the nanocarrier for drug delivery [13, 14] This nanomaterial can be used as a photothermal agent and photosensitizer for cancer therapy because of its broad absorption across the infrared region and the ability to produce reactive oxygen species [15,16,17,18,19]. BP-Au NSs are fabricated via a one-step facile synthetic method (Scheme 1), whose product exhibits high-near infrared SERS activity to acquire the Raman fingerprints of cellular composition located around the nanohybrids. This feature allows the SERS technique to monitor the intracellular trajectory of BP-based nanohybrids.
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