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 scar-driven 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 µm). 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 chemo-photothermal therapy. The combination therapy reduced the IC50 value from 71.05 µM to 48.73 µM 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.

A 3D-Printed Graphene BioFuse Implant for Postsurgical Adjuvant Therapy of Cancer: Proof of Concept in 2D- and 3D-Spheroid Tumor Models.

Three-dimensional printing is an emerging technology that is finding its niche applications in diverse fields owing to its flexibility concerning personalization and design. Surgery followed by adjuvant therapy is the standard treatment plan in most cancers from stage I to stage III. Most of the available adjuvant therapies, like chemotherapy, radiation therapy, immunotherapy, hormonal therapy, etc., are associated with severe side effects that considerably reduce the quality of life of patients. In addition, there is always the chance of tumor recurrence or metastasis development followed by surgery. This investigation reports the development of a 3D-printed, biodegradable, laser-responsive implant with a chemo-combined thermal ablating potential for adjuvant therapy of cancer. The 3D-printable ink was developed using poly(l-lactide) and hydroxypropyl methylcellulose as the base polymer, doxorubicin as the chemotherapeutic agent, and reduced graphene oxide as the photothermal ablating agent. The personalized implant released the drug pH-dependently (p value < 0.0001) for an extended period (93.55 ± 1.80% → 28 days). The 3D-printed implant exhibited acceptable biophysical properties (tensile strength: 3.85 ± 0.15 MPa; modulus: 92.37 ± 11.50 MPa; thickness: 110 µm) with laser-responsive hyperthermia (ΔT: 37 ± 0.9 °C → 48.5 ± 1.07 °C; 5 min; 1.5 W/cm2) and inherent biodegradable property (SEM analysis). The 3D-printed implant was evaluated for its therapeutic potential in 2D- and 3D-spheroid tumor models (MDA-MB 231 and SCC 084 2D cells) employing MTT cytotoxicity assay, apoptosis assay, cell cycle analysis, and gene expression analysis. The biomolecular aspects and biomechanics of the 3D-printed BioFuse implant were also evaluated by determining the effect of treatment on the expression levels of HSP1A, Hsp70, BAX, and PTEN. It is advocated that the knowledge developed in this project will significantly assist and advance the science aiming to develop a clinically translatable postsurgical adjuvant therapy for cancer.

Laser activatable nanographene colloids for chemo-photothermal combined gene therapy of triple-negative breast cancer.

This investigation reports the green approach for developing laser activatable nanoscale-graphene colloids (nGC-CO-FA) for chemo-photothermal combined gene therapy of triple-negative breast cancer (TNBC). The nano colloid was found to be nanometric as characterized by SEM, AFM, and zeta sizer (68.2 ± 2.1 nm; 13.8 ± 1.2 mV). The doxorubicin (Dox) loaded employing hydrophobic interaction/π-π stacking showed >80% entrapment efficiency with a sustained pH-dependent drug release profile. It can efficiently incorporate siRNA and Dox and successfully co-localize them inside TNBC cells to obtain significant anticancer activity as evaluated using CCK-8 assay, apoptosis assay, cell cycle analysis, cellular uptake, fluorescence assay, endosomal escape study, DNA content analysis, and gene silencing efficacy studies. nGC-CO-FA/Dox/siRNA released the Dox in temperature- and a pH-responsive manner following NIR-808 laser irradiation. The synergistic photo-chemo-gene therapy using near infrared-808 nm laser (NIR-808) irradiation was found to be more effective as compared to without NIR-808 laser-treated counterparts (∆T: 37 ± 1.1 °C → to 49.2 ± 3.1 °C; 10 min; 0.5 W/cm2), suggesting the pivotal role of photothermal combined gene-therapy in the treatment of TNBC.

Integrated nanomaterials for non-invasive photothermal therapy of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that causes swelling, redness, and arthralgia of multiple joints. Despite significant research and development on the treatment modalities for RA, there is still no established effective treatment option for eradicating joint damage and inflammation. In recent years, photothermal therapy (PTT) has emerged as a practical approach to treat RA. In this review, we outline various factors that affect the effective treatment of RA. Moreover, we discuss various PTT-based nanomaterials that can be used to treat RA.

Green graphene nanoplates for combined photo-chemo-thermal therapy of triple-negative breast cancer.

Aim: Green graphene oxide (GO) nanoplates, which are reduced and stabilized by quercetin and guided by folate receptors (quercetin reduced and loaded GO nanoparticles-folic acid [FA]), were developed to mediate combined photo-chemo-thermal therapy of triple-negative breast cancer. Materials & methods: Modified Hummers method was used for the synthesis of GO followed by its reduction using quercetin, FA was then conjugated as a targeting ligand. A cytotoxicity assay, apoptosis assay and cellular uptake assay were performed in vitro in MDA-MB-231 cell line with and without irradiation of a near-infrared 808 nm laser. Results & conclusion: Quercetin reduced and loaded GO nanoparticles-FA showed significantly high cellular uptake (p < 0.001) and cytotoxic effects in MDA-MB-231 cells, which was even more prominent under the situation of near-infrared 808 nm laser irradiation, making it a potential option for treating triple-negative breast cancer.

Nanostructured Hyaluronic Acid-based Materials for the Delivery of siRNA.

BACKGROUND: The search for the effective treatment strategies to combat a disease that is characterized by abnormal cell growth and known as cancer is still required to reach its destiny. To address the problem, recently several gene therapies based on novel RNA interference (RNAi) have been proposed such as siRNA, micro RNA, shRNA, etc. out of which, siRNAs (silencing RNA) promises to show significant progress in pharmacotherapy, including considerable expansion of the druggable target space and the possibility of treating cancer. METHODS: This review aims to uncover the hyaluronic acid (HA) and HA-hybridized nanoplatforms for siRNA delivery systems with a particular focus on the discussion of available reports while addressing the future potential of HA-based treatment strategies. RESULTS: HA modified siRNA delivery, as promised, provided better targeting potential in many types of cancers. In addition, it was able to modify the release of siRNA as well. Toxicity of HA is well mentioned however, the loophole is yet to be filled by exploring various remedies for overcoming toxicity. CONCLUSION: To overcome the problems associated with these emerging genetic tools, investigators have employed glycosaminoglycan HA-based biopolymers. This biopolymer offers a variety of properties such as biodegradability, biocompatibility, aqueous solubility, viscoelasticity, and non-immunogenicity.