Dual Functional Magnetic Nanoparticles Conjugated with Carbon Quantum Dots for Hyperthermia and Photodynamic Therapy for Cancer

Abstract

The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.

Keywords: cancer; hyperthermia; magnetic nanoparticles; nanoparticles; photodynamic therapy; quantum dots.

Figure 1

Schematic illustration showing the synthesis procedure of magnetic nanoparticles conjugated with carbon quantum dots (M-CQDs) for dual magnetic hyperthermia and photodynamic therapy for cancer.

Figure 2

UV-Visible spectra of (a) A-CQDs with λ_max of 288, the inserted images represent the florescence (blue color) under UV light exposer, while light yellow bottle is at normal environment and (b) fluorescence excitation-emission spectra of A-CQDs shows the excitation dependent emissions.

Figure 3

Zeta potential of (a) MNPs (-33.2), (b) A-CQDs (11.6), and (c) M-CQDs QDs conjugate (-23.2), the decreased negative charge in M-CQDs resulted from conjugation of A-CQDs and b) UV-Vis spectra of A-CQDs, MNPs, and M-CQDs.

Figure 4

FT-IR spectra of (a) A-CQDs, (b) MNPs, and (c) conjugated QDs and MNPs (M-CQDs).

Figure 5

Energy dispersive spectra of (a), A-CQDs (b)MNPs, and (c) M-CQDs.

Figure 6

Heating profiles under alternating magnetic field of (a) MNPs and (b) M-CQDs. At low frequency the magnetic fluid shows higher SAR and therapeutic heating for longer time.

Figure 7

TEM images of (a) A-CQDs of size ~2-8 nm with spherical shape, (b) MNPs with size of 10-20 nm, and (c) M-CQDs of size 20-30 nm, shows conjugated CQDs on top of MNPs the yellow circle represents the M-CQDs, where the red arrows show the CQDs with light grey, while dark black particles are MNPs.

Figure 8

Cell viability analysis of (a) A-CQDs, (b) MNPs, (c) M-CQDs, and (d) Cell viability under different therapeutic conditions through MTT assay. Quantitative estimation of reactive oxygen species of (e) A-CQDs and (f) M-CQDs through NBT assay. All the data expressed as mean ± SEM and analysed for statistical significance using one way ANOVA with Tukey post-test Comparison Test, n=3, * vs Control. **p<0.01, ***p< 0.001.

Figure 9

Fluorescence images of A549 cells treated with PDT, hyperthermia, and PDT+ hyperthermia using CLSM (Scale bar: 100 µm).

Figure 10

In vivo anti-tumor activity of M-CQDs with MHT and PDT. (a) Animal study design, (b) Representative IVIS imaging of the animals with different treatment application, (c) Tumor area reduction after the different treatments. All the data expressed as mean ± SEM and analysed for statistical significance using one way ANOVA with Tukey post-test Comparison Test, n=3, * vs Control. **p<0.01, ***p< 0.001.