The preparation of multifunctional smart theranostic
systems is
commonly achieved through complicated strategies, limiting their biomedical
applications. Spirulina platensis (SP) microalgae,
as a natural helix with some of the intrinsic theranostic functionalities
(e.g., fluorescent and photosensitizer pigments), not only facilitates
the fabrication process but also guarantees their biosafety for clinical
applications. Herein, the helical architecture of gold nanoparticles
(AuNPs) based on a SP biotemplate was engineered as a safe, biodegradable,
and tumor-targeted biohybrid for imaging-guided photothermal therapy
(PTT) to combat triple-negative breast cancer. The quasi-spherical
AuNPs were embedded throughout the SP cell (Au-SP) with minimally
involved reagents, only by controlling the original morphological
stability of SP through pH adjustment of the synthesis media. SP thiolation
increased the localization of AuNPs selectively on the cell wall without
using a reducing agent (Au-TSP). SP autofluorescence, along with the
high X-ray absorption of AuNPs, was employed for dual-modal fluorescence
and computed tomography (FL/CT) imaging. Furthermore, the theranostic
efficacy of Au-SP was improved through a targeting process with folic
acid (Au-SP@CF). High tumor inhibition effects were obtained by the
excellent photothermal performance of Au-SP@CF in both in
vitro and in vivo analyses. Of particular
note, a comparison of the photothermal effect of Au-SP@CF with the
naked SP and calcined form of Au-SP@CF not only indicated the key
role of the helical architecture of AuNPs in achieving a high photothermal
effect but also led to the formation of new gold microspiral biohybrids
(Au-MS) over the calcination process. In short, well-controllable
immobilization of AuNPs, appropriate biodegradability, good hemocompatibility,
long-term biosafety, accurate imaging, high tumor suppression, and
low tumor metastasis effects under laser irradiation are an array
of intriguing attributes, making the proposed biohybrid a promising
theranostic system for FL/CT-imaging-guided PTT.
Dopamine
is one of the most important neurotransmitters released
by neurons in the central nervous system, and a variety of neurological
illnesses and mental disorders are associated with impairments in
the secretion and functionality of dopamine. Dopamine, depending on
the type of receptors, can act as a stimulant or an inhibitor. In
this study, dendrimer-conjugated dopamine was utilized as a chelating
agent for Technetium-99m to investigate the organ distribution of
this compound in vivo using the single-photon emission
computed tomography (SPECT) technique. For this purpose, dendrimers
were synthesized using polyethylene glycol diacid and citric acid
precursors, and dopamine was conjugated to the dendrimer using EDC/NHS
cross-linker. The results showed no sign of toxicity of the dopamine-functionalized
dendrimers on HEK-293 cell lines. The optimization of labeling conditions
was conducted using the experimental design method (i.e., conjugate
value, pH, and the amount of reducing agent), and then labeling efficiency
was evaluated by thin-layer chromatography (TLC). Finally, the study
of organ distribution in normal mice using SPECT imaging and comparing
it with gene expression in different organs revealed that dopamine
D1 receptors exhibited the highest accumulation in the liver and that
the drug retained its specificity.
Axillary lymph node detection is crucial to staging and prognosis of the lymph node metastatic spread in breast cancer. Currently, lymphoscintigraphy and blue dye, as the conventional methods to localize sentinel lymph nodes (SLNs), are invasive and can only be performed during surgery. This study has had a novel hybrid gadolinium oxide nanoparticle coating with Cyclodextrin-based polyester as a high-relaxivity T1 magnetic resonance molecular imaging (MRMI) contrast agent (CA). Twelve female BALB/c mice were randomly divided into three groups of four mice; each group was injected with 4T1 cells to obtain metastasis lymph nodes and diagnosed by using the 3D T1W (VIBE) MRI (Siemens 3T, Prisma). The synthesized Gd2O3@PCD nanoparticles with a suitable particle size range of 20–40 nm have had much higher longitudinal relaxivity (r1) for Gd2O3@PCD and Gd-DOTA (Dotarem) with the values of 3.98 mM−1·s−1 ± 0.003 and 2.71 mM−1·s−1 ± 0.005, respectively. Identical MR images in coronal views were subsequently obtained to create time-intensity curves of the right axillary lymph nodes and to measure the contrast ratio (CR). The peak CR and qualitative assessment of axillary lymph nodes at five-time points were evaluated. After subcutaneous injection, the contrast ratio of axillary lymph node and tumor in mice exhibited CR peak of Gd2O3@PCD and Dotarem with the values of 2.21 ± 0.06 and 0.40 ± 0.004 for lymph node and 2.54 ± 0.04 and 1.21 ± 0.007 for the tumor, respectively. Furthermore, the lumbar-aortic lymph node is weakly visible in the original coronal image. In conclusion, the use of Gd2O3@PCD nanoparticles as novel MRMI CAs enables high resolution for the detection of lymph node metastasis in mice with the potential capability for breast cancer diagnostic imaging.
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