Zhili Peng

Transferrin conjugated nontoxic carbon dots for doxorubicin delivery to target pediatric brain tumor cells

Among various cancers, pediatric brain tumors represent the most common cancer type in children and the second most common cause of cancer related deaths. Anticancer drugs and therapies, such as doxorubicin (Dox), have severe side effects on patients during chemotherapy, especially for children as their bodies are still under development. These side effects are believed to be due to the lack of a delivery system with high efficacy and targeting selectivity, resulting in serious damages of normal cells. To improve the efficacy and selectivity, the transferrin (Trans) receptor mediated endocytosis can be utilized for drug delivery system design, as transferrin receptors are expressed on the blood brain barrier (BBB) and often over expressed in brain tumor cells. Carbon dots (C-Dots) have recently emerged as benign nanoparticles in biomedical applications owing to their good water solubility, tunable surface functionalities and excellent biocompatibility. The unique characteristics of C-Dots make them promising candidates for drug delivery development. In this study, carbon dots-transferrin-doxorubicin covalent conjugate (C-Dots-Trans-Dox) was synthesized, characterized by different spectroscopic techniques and investigated for the potential application as a drug delivery system for anticancer drug doxorubicin to treat pediatric brain tumors. Our in vitro results demonstrate greater uptake of the C-Dots-Trans-Dox conjugate compared to Dox alone presumably owing to the high levels of transferrin receptors on these tumor cells. Experiment showed that C-Dots-Trans-Dox at 10 nM was significantly more cytotoxic than Dox alone, reducing viability by 14-45%, across multiple pediatric brain tumor cell lines.

Method to Determine Protein Concentration in the Protein-Nanoparticle Conjugates Aqueous Solution Using Circular Dichroism Spectroscopy

Considerable efforts have been made to synthesize and characterize protein-nanoparticle conjugates (protein-NPs) for their promising applications in bionanotechnology. However, protein concentration determination in the protein-NPs has so far not been reported. In this Letter, we present a simple and nondestructive approach to quantify the protein concentration in the protein-NPs aqueous solution using circular dichroism (CD) spectroscopy. Carbon dots (∼4 nm), gold nanoparticles (∼10 nm), and polyethylene glycol (PEG, molecular weight ∼3000) were either physically mixed or covalently conjugated (not in the case of gold nanoparticles) with proteins (human transferrin, human serum albumin, and ovalbumin). We were able to quantify the protein concentration in the protein-nanoparticle conjugates using a calibration curve from the CD spectra.

Interactions between Carbon Nanomaterials and Biomolecules

Interactions between carbon nanomaterials, including carbon dots, fullerene, carbon nanotube, graphene, and graphene oxide, and biomolecules play an important role in the field of nanobiotechnology. Due to the unique properties of carbon nanomaterials and the magnificent features of their colloids, it shows high potential in fibrillation inhibition, high sensitivity sensor fabrication, bioimaging, drug delivery, and other areas. Hereby, we will go over different families of carbon nanomaterials regarding to the interaction between carbon nanomaterials and biomolecules at the interface, and their applications will be reviewed as well.

Crossing the blood-brain-barrier with transferrin conjugated carbon dots: A zebrafish model study.

Drug delivery to the central nervous system (CNS) in biological systems remains a major medical challenge due to the tight junctions between endothelial cells known as the blood-brain-barrier (BBB). Here we use a zebrafish model to explore the possibility of using transferrin-conjugated carbon dots (C-Dots) to ferry compounds across the BBB. C-Dots have previously been reported to inhibit protein fibrillation, and they are also used to deliver drugs for disease treatment. In terms of the potential medical application of C-Dots for the treatment of CNS diseases, one of the most formidable challenges is how to deliver them inside the CNS. To achieve this in this study, human transferrin was covalently conjugated to C-Dots. The conjugates were then injected into the vasculature of zebrafish to examine the possibility of crossing the BBB in vivo via transferrin receptor-mediated endocytosis. The experimental observations suggest that the transferrin-C-Dots can enter the CNS while C-Dots alone cannot.

Determination of the composition, encapsulation efficiency and loading capacity in protein drug delivery systems using circular dichroism spectroscopy.

Peptides and proteins have become very promising drug candidates in recent decades due to their unique properties. However, the application of these drugs has been limited by their high enzymatic susceptibility, low membrane permeability and poor bioavailability when administered orally. Considerable efforts have been made to design and develop drug delivery systems that could transport peptides and proteins to targeted area. Although it is of great importance to determine the composition after loading a drug to the carrier, the ability to do so is significantly limited by current analytical methods. In this letter, five important proteins, α1-antitrypsin, hemoglobin human, human serum albumin, human transferrin and r-globulin were chemically conjugated to two model drug carriers, namely carbon dots and polymer O-(2-carboxyethyl) polyethylene glycol. A simple yet convenient method based on circular dichroism spectroscopy was developed to determine the compositions of the various protein-carrier conjugates.

Polymers in Carbon Dots: A Review

Carbon dots (CDs) have been widely studied since their discovery in 2004 as a green substitute of the traditional quantum dots due to their excellent photoluminescence (PL) and high biocompatibility. Meanwhile, polymers have increasingly become an important component for both synthesis and modification of CDs to provide polymeric matrix and enhance their PL property. Furthermore, critical analysis of composites of CDs and polymers has not been available. Herein, in this review, we summarized the use of polymers in the synthesis and functionalization of CDs, and the applications of these CDs in various fields.

Recent Progress Toward the Spectroscopic Analysis of Biomacromolecule–Nanoparticle Interactions

The application of nanoparticles (NPs) for biomedical use is one of the fastest growing fields in science. The great potential has attracted attention from many fields, including chemistry, biology, medicine, and engineering. However, with relatively little understanding of biomacromolecule–NP interactions, there are increasing safety concerns about the use of nanomaterials in biomedical fields. To determine the biocompatibility of NPs and evaluate their nanosafety, great efforts are currently being made on investigating biomacromolecule–NP interactions. Spectroscopic methods and strategies play an important role in these investigations to help us understand the mechanistic basis for the biological activity of NPs, which is essential for the safe application of nanotechnology. Herein, in this chapter, we summarize the recent progress in the study of protein–NP, DNA–NP, and lipid–NP interactions based on various spectroscopic techniques.