Multifunctional Gold Helix Phototheranostic Biohybrid That Enables Targeted Image-Guided Photothermal Therapy in Breast Cancer

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.