Precisely designed protein-based nanodrugs, as a kind of colloidal drug system, have attracted significant attention in tumor therapy because of their refined drug loading ratio, controlled delivery efficacy and natural biocompatibility. However, most drugs are conjugated to the protein carriers randomly without specific binding sites. Moreover, such sites could easily be replaced by lipophilic molecules in the physiological environment and result in low delivery efficiency. With strong and specific binding locations especially comparatively narrow spatial binding sites and nonflexible structure, hemin (FePPIX)-free hemoglobin or apohemoglobin (apoHb), as a natural metalloporphyrin protein carrier, represents great potential in bioapplication. Therefore, we herein introduce a folate acid (FA) modified, zinc-substituted hemoglobin (ZnPHb-FA) as a naturally occurring protein matrix-based photosensitizer for cancer photodynamic therapy (PDT). Noncovalent inserted ZnPPIX molecules in apoHb possess an extremely stable property and significant recovered photoproperties with superior biocompatibility and phototoxicity, both in vitro and in vivo. This stability was verified by molecular docking analysis and calculation of binding constant, representing a total of five drug binding sites of apoHb for ZnPPIX molecules, four of which are energetically favorable (△G value of -11.9 kcal/mol), and one which is energetically acceptable (△G value of -9 kcal/mol). Folate acid modification has been shown to efficiently enhance the internalization and retention time of ZnPHb nanodrug. ZnPHb-FA is also an efficient depressor of hemin oxygenase-1 (HO-1), which could, in turn, lower the antioxidant ability of cancer cells by decreasing the production of bilirublin. Results in vitro and in vivo both indicated that the firmly combination of apoHb and ZnPPIX described here represents a novel and efficient protein nanodrug systems for cancer therapy.

As Interface mediated self-assembly of nanocrystals provide excellent strategy for sensing, catalysis or photonics, the construction of innovative interfaces and development of versatile strategies for nanocrystal synthesis are urgently needed. Herein, latent fingerprints (LFPs), the most common markers for human identity, are used as naturally accessible interface for organization of graphene isolated nanocrystals (GINs). Excitingly, the selective adsorption of GINs on lipidic ridge provides a universal approach for the in-situ construction of the plasmonic arrays. Such system with intrinsic chrominance and Raman signal enables the high resolution colorimetric and surfaced-enhanced Raman spectroscopy (SERS) dual-mode imaging, which can detail the structures of the LFPs from 1st to 3rd level even the LFPs are shielded. Furthermore, the interface can be constructed on diverse materials by a simple finger-pressing process and the densely packed arrays can serve as superior SERS substrate for label-free, non-invasive acquisition of molecule information especially residues in LFPs. The combination of chemical composition with detailed structures efficiently recognizes the human identity and could help link it to a crime scene. Overall, the LFPs can act as natural platform for interface mediated localized assembly and personalized information acquisition for forensic science or precise medicine.

Pathogenic oral biofilms especially acid-producing ones cause a variety of oral diseases such as dental caries. Given that bacteria are embedded within the biofilms matrix to prevent the penetration of therapeutic drugs, people have explored the applications of nanoparticles to treat oral diseases. However, current nanoparticle-mediated eradication has not achieved the precise treatment of biofilms, and the stabilities of nanoparticles go on strike because of acidic environment leading to poor therapeutic effectiveness. Herein, we design an integrated nanozyme, CoPt@graphene@glucose oxidase (CoPt@G@GOx), which has cascade reaction activity with two-step process. Hydrogen peroxide (H₂O₂) produced through the glucose oxidation by GOx serves as the substrate for peroxidase-mimic CoPt@G to produce highly toxic hydroxyl radical under acidic environment. Compared to the simple mixture of GOx and CoPt@G, CoPt@G@GOx shows around fourfold catalytic effect enhancement. Meanwhile, CoPt@G@GOx can precisely target the location of the biofilms, which ensures the minimal impact on normal soft-tissues. Relying on the advantage of the magneto-actuated cascade catalytic activity, CoPt@G@GOx reveals a superior antibacterial ability in the Streptococcus mutans biofilms model. Thus, our results provide an easy and effective method to exploit bifunctional nanozyme as a novel topical agent to prevent the prevalent biofilm-induced oral disease.

Aptamer guided nanomedicine shows great promise in targeted cancer therapies. However the loss of targeting capacity during in vivo or clinical trials has largely hindered its popularity and there are no systematic studies to elucidate the causes. Herein, we investigated such loss of targeting capacity by examining how the physiological milieu affected targeting effect. Aptamer functionalized gold nanoparticle (AuNP) was chosen as the model and exposed to human blood serum that is used to mimic physiological milieu. Dynamic light scattering (DLS), flow cytometry and label-free liquid chromatography tandem mass spectrometry (LC-MS/MS) were employed to determine variations of NPso surface chemistry and biological identities changes after serum exposure. Results showed that the targeting ability loss was caused by protein corona blocking, replacement and enzymatic cleavage of surface aptamer targeting ligands. Noteworthy, the aggregation issue is critical for the smaller NPs. Analysis of the protein corona profile indicated the accumulation of immune-related proteins on the surface of aptamer-conjugated NPs, which could induce immune response, resulting in rapid clearance of NPs.

Graphitic nanomaterials have unique, strong, and stable Raman vibrations that have been widely applied in chemistry and biomedicine. However, utilizing them as internal standards (ISs) to improve the accuracy of surface-enhanced Raman spectroscopy (SERS) analysis has not been attempted. Herein, we report the design of a unique IS nanostructure consisting of a large number of gold nanoparticles (AuNPs) decorated on multilayered graphitic magnetic nanocapsules (AGNs) to quantify the analyte and eliminate the problems associated with traditional ISs. The AGNs demonstrated a unique Raman band from the graphitic component, which was localized in the Raman silent region of the biomolecules, making them an ideal IS for quantitative Raman analysis without any background interference. The IS signal from the AGNs also indicated superior stability, even under harsh conditions. With the enhancement of the decorated AuNPs, the AGN nanostructures greatly improved the quantitative accuracy of SERS, in particular the exclusion of quantitative errors resulting from collection loss and non-uniform distribution of the analytes. The AGNs were further utilized for cell staining and Raman imaging, and they showed great promise for applications in biomedicine.