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.

Current Update on Transcellular Brain Drug Delivery.

It is well known that the presence of a blood-brain barrier (BBB) makes drug delivery to the brain more challenging. There are various mechanistic routes through which therapeutic molecules travel and deliver the drug across the BBB. Among all the routes, the transcellular route is widely explored to deliver therapeutics. Advances in nanotechnology have encouraged scientists to develop novel formulations for brain drug delivery. In this article, we have broadly discussed the BBB as a limitation for brain drug delivery and ways to solve it using novel techniques such as nanomedicine, nose-to-brain drug delivery, and peptide as a drug delivery carrier. In addition, the article will help to understand the different factors governing the permeability of the BBB, as well as various formulation-related factors and the body clearance of the drug delivered into the brain.

Recent advancements and future submissions of silica core-shell nanoparticles.

The core-shell silica-based nanoparticles (CSNPs) possess outstanding properties for developing next-generation therapeutics. CSNPs provide greater surface area owing to their mesoporous structure, which offers a high opportunity for surface modification. This review highlights the potential of core-shell silica-based nanoparticle (CSNP) based injectable nanotherapeutics (INT); its role in drug delivery, biomedical imaging, light-triggered phototherapy, Plasmonic enhancers, gene delivery, magnetic hyperthermia, immunotherapy, and potential as next-generation theragnostic. Specifically, the conceptual crosstalk on modern synthetic strategies, biodistribution profiles with a mechanistic view on the therapeutics loading and release modeling are dealt in detail. The manuscript also converses the challenges associated with CSNPs, regulatory hurdles, and their current market position.

Biosimilars accessible in the market for the treatment of cancer.

Biosimilars are the biological product clinically identical to a biologic reference standard regarding their strength, purity, and safety. A large segment of biosimilars has been developed for the treatment of cancer. This review aims to discuss various facets of biosimilars and explicates on biosimilars accessible in the market for cancer clinical intervention. It also illustrates the outcomes of recent clinical trial studies concerning biosimilars. Further, it also crosstalk the safety profiles, regulatory approval requirements, and allied challenges therein. The work will be of significant interest to researchers working in the field of biologics and biosimilars.

Reinforced electrospun nanofiber composites for drug delivery applications.

Electrospun technology becomes a valuable means of fabricating functional polymeric nanofibers with distinctive morphological properties for drug delivery applications. Nanofibers are prepared from the polymer solution, which allows the direct incorporation of therapeutics such as small drug molecules, genes, and proteins by merely mixing them into the polymeric solution. Due to their biocompatibility, adhesiveness, sterility, and efficiency in delivering diverse cargoes, electrospun nanofibers have gained much attention. This review discusses the capabilities of the electrospun nanofibers in delivering different therapeutics like small molecules, genes, and proteins to their desired target site for treating various ailments. The potential of nanofibers in administering through multiple administration routes and the associated challenges has also been expounded along with a cross-talk about the commercial products of nanofibers for biomedical applications.

Nanomedicines accessible in the market for clinical interventions.

Nanomedicines refers to nanotechnology inspired pharmaceutical products often referred to as 'nanopharmaceuticals.' It has displayed commendable potential in enhancing therapeutic efficacy as well as in reducing the side effects associated with conventional drug counterpart. Recent years have monitored the entry of a large amount of nanomedicine in the market with an appreciable market share to date. Despite this, the development of nanomedicine is posing challenges (i.e., safety, regulatory hurdles, cost, scale-up issues, etc.) that need to be resolved for their market entry. This review presents a cross-sectional discussion on the nanomedicine-derived products available in the market for both clinical and diagnostic applications. An overview of its market potential, market size, and the products that are currently in the clinical stages is also provided. The review also expounds on the challenges faced by nano-drug products at the time of their commercialization.

Exosomes in multidrug-resistant cancer.

Multiple drug resistance (MDR) is a significant challenge in the treatment of cancer using chemotherapy. There are numerous reasons and mechanisms that are responsible for the development of MDR in cancer tissues. Further, exosomes and its constituents also play a vital role in limiting the efficacy of chemotherapeutic agents. Exosomes are well known for their role in developing resistance in addition to promoting tumor advancement and metastasis. This review discusses the role of exosomes in the development of drug resistance along with their allied mechanisms. This review also discusses the upregulation and downregulation of various exosomal components, which can be effectively employed as diagnostic biomarkers in the treatment of cancer. The essential applications of exosomes to treat drug-resistant cancer have also been discussed.