Plasmonic laser-responsive BioDissolve 3D-printed graphene@cisplatin-implant for prevention of post-surgical relapse of oral cancer

The development of chemoresistance is a major obstacle in post-surgical adjuvant therapy of cancer, leading to cancer cell survival, recurrence, and metastasis. This study reports a 3D-printed plasmonic implant developed for the post-surgical adjuvant therapy of cisplatin-resistant cancer cells to prevent relapse. The implant was printed using optimized biomaterial ink containing biodegradable polymers [poly(L-lactide) and hydroxypropyl methylcellulose] blended suitably with laser-responsive graphene and chemo drug (Cisplatin). The irradiation of scardriven 3D-printed implant with a laser stimulates graphene to generate a series of hyperthermia events leading to photothermolysis of cisplatin-resistant cancer cells under the combined influence of sustained cisplatin release. The developed personalized implant offers pH-responsive sustained drug release for 28 days. The implant exhibited acceptable biophysical properties (Tensile strength: 3.99 +/- 0.15 MPa; modulus: 81 +/- 9.58 MPa; thickness: 110 mu m). The 3D-printed implant effectively reverses the chemoresistance in cisplatin-resistant 3D spheroid tumor models. Cytotoxicity assay performed using cisplatin-resistant (CisR) cell line revealed that the cell viability was reduced to 39.80 +/- 0.68 % from 61.37 +/- 0.98 % in CisR tumor spheroids on combined chemophotothermal therapy. The combination therapy reduced the IC 50 value from 71.05 mu M to 48.73 mu M in CisR spheroids. Apoptosis assay revealed an increase in the population of apoptotic cells (35.45 +/- 1.56 % -> 52.53 +/- 2.30 %) on combination therapy. A similar trend was observed in gene expression analysis, where the expression of pro-apoptotic genes Caspase 3 (3.73 +/- 0.04 fold) and Bcl-2-associated X protein (BAX) (3.35 +/- 0.02 fold) was increased on combination therapy. This 3D-printed, biodegradable implant with chemo-combined thermal ablating potential may provide a promising approach for the adjuvant treatment of resistant cancer.