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The extensive use of graphene-family nanomaterials (GFNs) in biomedicine and other fields has intentionally or unintentionally resulted in their introduction into the blood circulation system, but the effects of the biotransformation of GFNs in blood plasma on their biocompatibility, organ targeting, drug delivery and antitumor ability remain unclear. The present work discovered that GFN sheets were degraded in human blood plasma to holey sheets and aromatic hydrocarbons. The carbon atoms connected with oxygen-containing groups in the planes of GFNs were the initial attack sites for active substances (e.g., OH and O 2 - ) in blood plasma. Subsequently, CC/CC bonds were broken. The reaction rate depended strongly on the extent of oxidization of GFNs. The pristine GFNs caused secondary structure damage to proteins and disturbances of cellular metabolic pathways. In contrast, the biotransformed nanomaterials presented high biocompatibility and were located in and targeted different tissues from their pristine forms, which influenced specific organ targeting therapy. The biotransformed nanomaterials also exhibited higher efficiencies of drug delivery (drug release and location) and killing tumor cells in vitro and in vivo. These findings provide insights into the application of nanomaterials in human healthcare using biotransformed nanomaterials., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Baicalin (BAI) has been reported to exert antitumor effects. However, BAI has limited water solubility, non-specific tumor targeting, and low bioavailability, which severely limited its clinical application. The aim of this study was to develop folic acid (FA) covalently conjugated-polyamidoamine (PAMAM) dendrimers (PAMAM-FA) as carrier systems for improvement of water solubility and tumor-specificity of BAI, and study the role of generation on the physiochemical properties and biological effects of PAMAM-FA/BAI complexes. In this work, four generations of PAMAM-FA were synthesized to entrap BAI. The average sizes of G3-FA/BAI, G4-FA/BAI, G5-FA/BAI, and G6-FA/BAI complexes were 174.4nm, 184.5nm, 258.8nm, and 247.5nm, respectively, and the zeta potentials of four PAMAM-FA/BAI complexes were -2.9mV, -6.6mV, -9.3mV, -9.0mV, respectively. The entrapment efficiencies of four PAMAM-FA/BAI complexes were 91.1%, 53.5%, 80.3%, and 91.9%, respectively, and the drug loading of PAMAM-FA/BAI complexes were about 22%. The formed PAMAM-FA/BAI complexes allowed sustained release of BAI in acidic PBS (pH5.4). In cellular uptake assay, PAMAM-FA/BAI complexes demonstrated increased drug uptake level in folate receptor (FR)-positive Hela cancer cells than FR-negative A549 cells, and the cellular uptake efficiency of PAMAM-FA is closely related with the generation of PAMAM. The MTT assay results showed that PAMAM-FA/BAI complexes demonstrated enhanced toxicity against Hela cells than non-FA-modified PAMAM/BAI complexes, and the G6-FA/BAI demonstrated the best inhibition efficiency. The cell cycle and cell apoptosis analysis further demonstrated the tumor-specific therapeutic efficacy of PAMAM-FA/BAI. These results suggested that the PAMAM-FA have the potential for targeted delivery of BAI into cancer cells to enhance its anti-tumor efficacy., (Copyright © 2017 Elsevier B.V. All rights reserved.)