Breast cancer is one of the major lethal diseases. Surgery has been widely used to treat breast cancer. But surgery cannot resect all cancer cells in some cases, which may result in cancer recurrence. Recently, photothermal therapy, which is based on photothermal ablation of cancer cells, has been developed as a promising cancer therapeutic strategy. Until now, various photothermal conversion agents such as gold nanoparticles (AuNPs) have been explored. However, poor targeting capability and low accumulation of nanoparticles in cancer tissues need improving. To increase the accumulation of nanoparticles, AuNPs have been immobilized in 3D porous scaffolds for repeated heating and local photothermal therapy.
In this study, folic acid (FA), a frequently used targeting ligand for cancer cells enriched with FA receptors, was introduced into the composite porous scaffolds to enhance cancer cells' capture ability. The photothermal ablation ability of the composite scaffolds was investigated both in vitro and in vivo.
Firstly, the FA-gelatin conjugate was synthesized based on a reaction between folic acid (FA) and gelatin. Secondly, Gold nanoparticles (AuNPs) with different shapes (nanorod, nanostar) and different sizes (around 40.0 nm, 70.0 nm, and 110.0 nm) were synthesized by a seed growth method. The one-pot method was used for the synthesis of Au nanorods with a longitudinal length of 110 nm. Finally, the ice particulates porogen method was used to prepare FA-functionalized composite porous scaffolds embedded with FA-gelatin-coated AuNPs with different shapes and sizes.
[Results and Discussion]
The UV-VIS spectra indicated the FA-gelatin conjugate was synthesized and their conjugate rate was calculated and optimized. The TEM images showed the morphology and size of synthesized AuNPs. The UV-VIS spectra of AuNPs showed AuNR possessed two LSPR peaks and AuNS had an abroad LSPR peak, which might be useful for photothermal therapy.
The SEM images showed the composite scaffolds had spherical large micropores with good interconnectivity. The photothermal conversion curves showed photothermal-induced temperature changes of composite scaffolds was modulated with the different shape and size of embedded AuNPs. The FA introduced in composite scaffolds showed high tumor cell capture ability compared with control groups. The photothermal ablation efficiency of tumor cells was dependent on the photothermal performance of the composite scaffolds. The results indicated FA-functionalized AuNRs 70-gelatin composite scaffolds had a good tumor cell capture and photothermal ablation ability. For the in vivo experiments, temperature monitor during laser irradiated implantation site of mice showed that the temperature of implanted scaffolds without AuNPs was kept almost unchanged. In contrast, the temperature of composite scaffolds embedded with AuNPs was increased significantly. Besides, whole-body bioluminescence imaging showed the in vivo tumor cell ablation effect.