Theranostics-embedded multifunctional tissue engineering scaffolds for cancer detection and treatment

Abstract

Electrospun nanofibrous scaffolds are popularly used in tissue engineering owing to their distinctive advantages. For post-surgery cancer patients, these scaffolds can be employed to regenerate tissue at the original tumor site after tumor resection. The high recurrence rate of cancer threatens lives of post-surgery patients, and hence effective detection and treatment of recurrent cancer become vitally important. In recent years, gold nanoparticle (AuNP)-based theranostics have attracted great attention for cancer detection and treatment due to their unique properties including surface enhanced Raman scattering (SERS) effect. The strongly amplified SERS signals can be used for high-sensitivity cancer detection. Additionally, AuNP-based theranostics can convert light into heat, providing photothermal therapy for cancers. In this study, multifunctional tissue engineering scaffolds incorporated with AuNP-based theranostics were fabricated, aiming to achieve both tissue regeneration and detection and treatment of recurrent cancer. Folic acid-conjugated chitosan (CS-FA) was firstly made and the folic acid ligand in CS-FA would provide cancer cell targeting ability. CS-FA-capped AuNPs (Au@CS-FA) were then synthesized with highly branched AuNP core and cross-linked CS-FA shell. A Raman reporter, Rhodamine 6G (R6G), was incorporated in Au@CS-FA for generating SERS signals. Concurrent electrospinning and co-axial electrospray were used to fabricate multifunctional scaffolds. Au@CS-FA theranostics were encapsulated in core-shell structured PLGA50/50 microspheres embedded in PLGA75/25 scaffolds. TEM and SEM results revealed that theranostics were well encapsulated in microspheres and the microspheres with uniform size were randomly distributed in scaffolds. In vitro immersion tests showed that controlled release of theranostics could be achieved when PLGA shell of microspheres gradually degraded. SERS measurements were conducted and high SERS signals by theranostics before encapsulation and after release were observed, indicating cancer detection ability of theranostics. In vitro biological experiments were conducted to investigate cancer cell targeting and photothermal treatment of released theranostics. The experiments used HeLa cells, which exhibited high-level folate-receptor expression, with MCF-7 cells as the control. It was shown that theranostics bounded to HeLa cells rather than MCF-7 cells. For HeLa cells treated with theranostics-incorporated scaffolds, after irradiation by a NIR laser, Live/Dead viability tests were conducted. High death rates of HeLa cells due to heat generated by theranostics were observed. In contrast, for HeLa cells irradiated under the same conditions but treated with PLGA scaffolds without theranostics, high degree of cell survival was observed. These results indicated that the released theranostics were effective photothermal agent for cancer treatment.