Impact of irradiation conditions on therapy of Lewis lung carcinoma in mice using glucose-ethylenediamine carbon dots

Abstract

Background: nowadays, the photoacoustic imaging is in the mainstream of cancer theranostics. In this study the nanoparticles with previously proven photoacoustic imaging properties, i.e. glucose-ethylenediamine carbon dots (GE-NPs), were tested for photoacoustic cancer therapy.

Methods: nanoparticle biocompatibility was analyzed in cell toxicity and neurotoxicity experiments ex vivo. Biochemical parameters were analyzed in animal experiments in vivo after intramuscular implantation of Lewis Lung carcinoma cells into the C57/Black mouse line.

Results: GE-NPs at concentrations of 0.1-1.0 mg/ml did not change the extracellular level, exocytotic and transporter-mediated release, as well as the initial rate of uptake and accumulation of L-[¹⁴C]glutamate in isolated rat brain nerve terminals. GE-NP-treated mice had evidence of the probable protection of the liver and attenuating the systemic consequences of tumor growth, as evidenced by normalization of serum aspartate aminotransferase (ASAT), and lactate dehydrogenase (LDH) levels, compared to vehicle-dosed tumor-bearing animals. According to hematological analysis, treatment with GE-NPs caused an increase in red blood cells and hematocrit up to the healthy control levels. When a combination of GE-NPs (1 mg/ml) is injected into a mouse tumor and the tumor is irradiated by a laser beam, it leads to an increase in mice survival by more than 30% compared to GE-NPs-treated non-irradiated mice, and a decrease in the growth rate of the cancerous tumor. The observed therapeutic effect can be related to the photoacoustically-induced destruction of cancer cells significantly enhanced by the presence of the incorporated GE-NPs, because the laser-induced localized heating of mice skin has not exceeded 2 °C.

Conclusions: the efficiency of photoacoustic therapy of Lewis Lung carcinoma in mice using biocompatible carbon dots was demonstrated. Biocompatible GE-NPs own multimodal potential in cancer theranostics, including both photoacoustic imaging and therapy, by applying different irradiation conditions.

Keywords: Carbon dots; Glucose-ethylenediamine; Lung carcinoma; Mice; Photoacoustic therapy.

Scheme 1

Roadmap of the experiments

Fig. 1

GE-NPs size distributions by number, found by the DLS (a) and zeta-potential distributions by ELS (b). Three measurements (for 1 min each) were performed for 5 mg/ml aqueous dispersion of GE-NPs nanoparticles

Fig. 2

Typical experimental set-up for photoacoustic measurements (a) schematic of tumor phantom and piezoelectric sensor with transparent buffer used (b) typical photoacoustic signal for 5 × 3 mm inclusion with different concentrations of GE-NPs inside the tissue phantoms (c)

Fig. 3

Experimental set-up for mice irradiating (a, b), typical image of laser beam spot on tumor site of alive (c) and died (d) LLC-bearing mouse obtained using Seek Thermal imager

Fig. 4

The dynamics of tumor growth and lung metastases count in LLC-bearing mice after treatment with GE-NPs

Fig. 5

Hematological parameters of LLC-bearing mice after vehicle or GE-NPs treatment compared to healthy control

Fig. 6

Biochemical parameters of LLC-bearing mice after vehicle or GE-NPs treatment compared to healthy control

Fig. 7

Mice survival for animals treated with Vehicle or GE-NPs and irradiated with nanosecond pulse laser for 5 and 10 min. Medians of survival and the significances of the difference are shown in Table 5

Fig. 8

The dynamics of tumor growth in LLC-bearing mice after single administration of GE-NPs accompanied with irradiation