Ultrasmall Carbon Nanodots as Theranostic Nanoheaters for Precision Breast Cancer Phototherapy: Establishing the Translational Potential in Tumor-in-a-Dish Models.

This study investigates the remarkable attributes of sulfur-doped carbon nanodots (CDs) synthesized in high yield and a narrow size distribution (4.8 nm). These CDs exhibit notable features, including potential bioelimination through renal clearance and efficient photothermal conversion in the near-infrared region with multicolor photoluminescence across the visible spectrum. Our research demonstrates high biocompatibility and effective near-infrared (NIR)-triggered photothermal toxicity when targeting mammospheres and patient-derived tumor organoids. Moreover, the study delves into the intricate cellular responses induced by CD-mediated hyperthermia. This involves efficient tumor mass death, activation of the p38-mitogen-activated protein kinase (MAPK) pathway, and upregulation of genes associated with apoptosis, hypoxia, and autophagy. The interaction of CDs with mammospheres reveals their ability to penetrate the complex microenvironment, impeded at 4 °C, indicating an energy-dependent endocytosis mechanism. This observation underscores the CDs' potential for targeted drug delivery, particularly in anticancer therapeutics. This investigation contributes to understanding the multifunctional properties of sulfur-doped CDs and highlights their promising applications in cancer therapeutics. Utilizing 3-D tumor-in-a-dish patients' organoids enhances translational potential, providing a clinically relevant platform for assessing therapeutic efficacy in a context mirroring the physiological conditions of cancerous tissues.

Polyamidoamine-Carbon Nanodot Conjugates with Bioreducible Building Blocks: Smart Theranostic Platforms for Targeted siRNA Delivery.

This study focuses on designing hybrid theranostic nanosystems, utilizing gadolinium-doped carbon nanodots decorated with bioreducible amphoteric polyamidoamines (PAAs). The objective is to synergize the exceptional theranostic properties of gadolinium-doped carbon nanodots (CDs) with the siRNA complexation capabilities of PAAs. Linear copolymeric polyamidoamines, based on N,N'-bis(acryloyl)cystamine, arginine, and agmatine, were synthesized, resulting in three distinct amphoteric copolymers. Notably, sulfur bridges within the PAA repeating units confer pronounced susceptibility to glutathione-mediated degradation─a key attribute in the tumor microenvironment. This pathway enables controlled and stimuli-responsive siRNA release, theoretically providing precise spatiotemporal control over therapeutic interventions. The selected PAA, conjugated with CDs using the redox-sensitive spacer cystamine, formed the CDs-Cys-PAA conjugate with superior siRNA complexing capacity. Stable against polyanion exchange, the CDs-Cys-PAA/siRNA complex released siRNA in the presence of GSH. In vitro studies assessed cytocompatibility, internalization, and gene silencing efficacy on HeLa, MCF-7, and 16HBE cell lines.

Microporous Fluorescent Poly(D,L-lactide) Acid-Carbon Nanodot Scaffolds for Bone Tissue Engineering Applications.

In this study, we introduce novel microporous poly(D,L-lactide) acid-carbon nanodot (PLA-CD) nanocomposite scaffolds tailored for potential applications in image-guided bone regeneration. Our primary objective was to investigate concentration-dependent structural variations and their relevance to cell growth, crucial aspects in bone regeneration. The methods employed included comprehensive characterization techniques such as DSC/TGA, FTIR, rheological, and degradation assessments, providing insights into the scaffolds' thermoplastic behavior, microstructure, and stability over time. Notably, the PLA-CD scaffolds exhibited distinct self-fluorescence, which persisted after 21 days of incubation, allowing detailed visualization in various multicolor modalities. Biocompatibility assessments were conducted by analyzing human adipose-derived stem cell (hADSC) growth on PLA-CD scaffolds, with results substantiated through cell viability and morphological analyses. hADSCs reached a cell viability of 125% and penetrated throughout the scaffold after 21 days of incubation. These findings underscore the scaffolds' potential in bone regeneration and fluorescence imaging. The multifunctional nature of the PLA-CD nanocomposite, integrating diagnostic capabilities with tunable properties, positions it as a promising candidate for advancing bone tissue engineering. Our study not only highlights key aspects of the investigation but also underscores the scaffolds' specific application in bone regeneration, providing a foundation for further research and optimization in this critical biomedical field.