A multifunctional ribonuclease A-conjugated carbon dot cluster nanosystem for synchronous cancer imaging and therapy

Abstract

Carbon dots exhibit great potential in applications such as molecular imaging and in vivo molecular tracking. However, how to enhance fluorescence intensity of carbon dots has become a great challenge. Herein, we report for the first time a new strategy to synthesize fluorescent carbon dots (C-dots) with high quantum yields by using ribonuclease A (RNase A) as a biomolecular templating agent under microwave irradiation. The synthesized RNase A-conjugated carbon dots (RNase A@C-dots) exhibited quantum yields of 24.20%. The fluorescent color of the RNase A@C-dots can easily be adjusted by varying the microwave reaction time and microwave power. Moreover, the emission wavelength and intensity of RNase A@C-dots displayed a marked excitation wavelength-dependent character. As the excitation wavelength alters from 300 to 500 nm, the photoluminescence (PL) peak exhibits gradually redshifts from 450 to 550 nm, and the intensity reaches its maximum at an excitation wavelength of 380 nm. Its Stokes shift is about 80 nm. Notably, the PL intensity is gradually decreasing as the pH increases, almost linearly dependent, and it reaches the maximum at a pH = 2 condition; the emission peaks also show clearly a redshift, which may be caused by the high activity and perfective dispersion of RNase A in a lower pH solution. In high pH solution, RNase A tends to form RNase A warped carbon dot nanoclusters. Cell imaging confirmed that the RNase A@C-dots could enter into the cytoplasm through cell endocytosis. 3D confocal imaging and transmission electron microscopy observation confirmed partial RNase A@C-dots located inside the nucleus. MTT and real-time cell electronic sensing (RT-CES) analysis showed that the RNase A@C-dots could effectively inhibit the growth of MGC-803 cells. Intra-tumor injection test of RNase A@C-dots showed that RNase A@C-dots could be used for imaging in vivo gastric cancer cells. In conclusion, the as-prepared RNase A@C-dots are suitable for simultaneous therapy and in vivo fluorescence imaging of nude mice loaded with gastric cancer or other tumors.

Characterization and Analytical Separation of Fluorescent Carbon Nanodots

“…Yang et al succeeded in using C-dots for the in vivo studies of optical imaging with mice for animal test. Followed by these, as a result of extensive and multidisciplinary efforts, C-dots have found their place in a wide range of applications in nanoprobes [56][57][58][59][60][61][62][63][64][65][66], drug delivery [67][68][69][70][71], therapy [72][73][74][75][76], and optoelectronic devices [77][78][79][80][81][82].…”

Progress of Luminescent Carbon Dots in Biomedicine Engineering

“…Top-down methods consist of arc discharge [1,5], laser ablation [6][7][8][9], and electrochemical oxidation [10][11][12][13], where the C-dots are formed or "broken off" from a larger carbon structure (such as graphite, carbon rods, graphene Oxides and carbon nanotubes). Bottom-up strategies consist, for example, of combustion/hydrothermal/ acidic oxidation/ultrasonic [14][15][16], supported synthetic [17,18], or microwave methods [19][20][21][22] during which the C-dots are formed from molecular precursors. Meanwhile, the nuance of reaction parameters during synthesis can tremendously affect on the properties of the C-dots, various carbon precursor and synthetic methods.…”

“…In our group, Liu, et al reported to synthesize fluorescent carbon dots (C-dots) with high quantum yields by using Ribonuclease A (RNaseA) as a stabilizer under microwave irradiation [21]. The preparation process and size, chemical and physical properties of C-dots have been shown in Fig.…”

“…Moreover, the emission wavelength and intensity of RNase A@ C-dots displayed a marked excitation wavelengthdependent character. Notably, the PL intensity is gradually decreasing as the pH increases, almost linearly dependent, and the as-prepared RNase A@ C-dots are suitable for simultaneous therapy and in vivo fluorescence imaging of nude mice loaded with gastric cancer or other tumors [21].…”

Synthesis of Fluorescent Carbon Dots by Gastrointestinal Fluid Treatment of Mongolia Har Gabur

“…The carboxyl groups on the surface of CDs enable them to have excellent water solubility and biocompatibility. In addition, the physical properties of CDs can be enhanced by chemically modifying the surface structure, for example, by applying a 2 Journal of Nanomaterials variety of organic, inorganic, and even biological molecules [5][6][7].…”