PEGylated carbon dot/MnO2 nanohybrid: a new pH/H2O2-driven, turn-on cancer nanotheranostics

Abstract

The effect of tumor-targeted photodynamic therapy (PDT) was improved by designing nanotheranostics to promote oxygenation in a tumor microenvironment (TME) wherein hypoxia, acidosis, and the elevated levels of H 2 O 2 are three main characteristics. In this study, a carbon dot (CD) PDT agent recently developed by our group was firstly applied as reducing agent to react with potassium permanganate for fabricating CDs/manganese dioxide (CDs/MnO 2) composites, which were in turn modified with polyethylene glycol (PEG) to form water-soluble CDs/MnO 2-PEG nanohybrids. In a normal physiological environment, the as-prepared nanohybrids exhibited quenched fluorescence, weak singlet oxygen generation, and low magnetic resonance imaging (MRI) signal. However, given the high sensitivity of MnO 2 to the TME, the CDs/MnO 2-PEG nanohybrids changed from an "off" to an "on" state with synchronously enhanced fluorescence, singlet oxygen generation, and MRI signal in the TME. In vitro and in vivo analyses have revealed that CDs/MnO 2-PEG nanohybrids could be applied as TME-driven, turn-on nanotheranostics for the MR/fluorescence bimodal imaging-guided PDT of cancer. Moreover, complete clearance of CDs/MnO 2-PEG nanohybrids from the body of mice was observed, indicating their low long-term toxicity and good biocompatibility. This work offers a new nanotheranostic candidate for modulating the unfavorable TME, particularly for the targeted PDT of cancer through precise positioning and oxygen generation.

Mn2+ complex-modified polydopamine- and dual emissive carbon dots based nanoparticles for in vitro and in vivo trimodality fluorescent, photothermal, and magnetic resonance imaging

“…After 12 h post-injection, mice were sacrificed and then primary organs (i.e., heart, liver, spleen, lung, and kidney) and tumors were harvested which were imaged to assess fluorescence intensities (Figure 6B). PDA@N-CDs(Mn) NPs mainly accumulated in the liver, lung, and kidney tissues (Figure 6C), which was similar to the previous research carbon nanosphere [39]. Stronger fluorescence signal could be found in tumor tissues than the spleen and heart by the time-dependent fluorescence intensity manner (Figure 6D).…”

Recent advance of carbon dots in bio-related applications

“…On the other hand, the tumor microenvironment is acidic (pH = 6.5-6.9) and high H 2 O 2 concentration (0.5 nmol/10 4 cells h −1 ). To solve the hypoxia problem, Wang's group [142] constructed the CDs/MnO 2 , MnO 2 can not only be reduced into Mn(II) by acidic H 2 O 2 as an T1 contrast agent for MRI but also generate oxygen within tumor to enhance the PDT efficiency. Magnetofluorescent Mn-CDs were prepared from Mn(II) phthalocyanine [143] and metal porphyrin [144][145][146].…”

Recent advances and prospects of carbon dots in cancer nanotheranostics

“…168,169 Recently, our group developed a CD/MnO 2 -PEG nanohybrid with previous PT2-CD PS as a reducing agent and potassium permanganate as an oxidation agent. 170 The as-prepared nanohybrids exhibit an ''off'' state in a normal physiological environment. However, given the high sensitivity of MnO 2 to a TME, CD/MnO 2 -PEG nanohybrids change from an ''off'' state to an ''on'' state with synchronously enhanced fluorescence, 1 O 2 generation, and MR imaging signal.…”