Immune checkpoint inhibitors and cancer immunotherapy by aptamers: an overview.

Efforts in cancer immunotherapy aim to counteract evasion mechanisms and stimulate the immune system to recognise and attack cancer cells effectively. Combination therapies that target multiple aspects of immune evasion are being investigated to enhance the overall efficacy of cancer immunotherapy. PD-1 (Programmed Cell Death Protein 1), CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4), LAG-3 (Lymphocyte-Activation Gene 3), and TIM-3 (T Cell Immunoglobulin and Mucin Domain-Containing Protein3) are all immune checkpoint receptors that play crucial roles in regulating the immune response and maintaining self-tolerance often exploited by cancer cells to evade immune surveillance. Antibodies targeted against immune checkpoint inhibitors such as anti-PD-1 antibodies (e.g., pembrolizumab, nivolumab), anti-CTLA-4 antibodies (e.g., Ipilimumab), and experimental drugs targeting LAG-3 and TIM-3, aim to block these interactions and unleash the immune system's ability to recognise and destroy cancer cells. The US FDA has approved different categories of immune checkpoint inhibitors that have been utilised successfully in some patients with metastatic melanoma, renal cell carcinoma, head and neck cancers, and non-small lung cancer. Although several immune checkpoint inhibitor antibodies have been developed, they exhibited immune-related adverse effects, resulting in hypophysitis, diabetes, and neurological issues. These adverse effects of antibodies can be reduced by developing aptamer against the target. Aptamers offer several advantages over traditional antibodies, such as improved specificity, reduced immunogenicity, and flexible design for reduced adverse effects that specifically target and block protein-protein or receptor-ligand interactions involved in immune checkpoint pathways. The current study aims to review the function of particular immune checkpoint inhibitors along with developed aptamer-mediated antitumor cytotoxicity in cancer treatment.

Antioxidant studies of chitosan nanoparticles containing naringenin and their cytotoxicity effects in lung cancer cells.

Chitosan based nano carrier systems have been widely explored owing to its reliability and simpler synthesis route. In the current study, chitosan (CS) encapsulated naringenin (NAR) nanoparticles (CS-NPs/NAR) were synthesized by ionic gelation method mediated by tripolyphosphate (TPP) as a cross-linker and characterized by DLS, SEM, Zeta potential, FT-IR and EDS analyses. The encapsulation efficiency of CS-NPs/NAR was determined by Folin-Ciocalteau (FC) and high performance liquid chromatography (HPLC) techniques. The native CS-NPs were found to be sized at 53.2 nm, while an increase in the size to 407.47 nm was observed upon loading with NAR. The encapsulation efficiency of CS-NPs/NAR was identified to be ∼70% by FC method and ∼80% by HPLC method, respectively. The release of NAR from CS-NPs/NAR in simulated gastric fluid was found to be ∼15% and remaining 85% of NAR was entrapped in CS-NPs/NAR. Furthermore, the free radical scavenging ability of CS-NPs/NAR was studied by Nitrate scavenging, 2, 2-diphenyl-2-picryl hydrazyl hydrate and hydroxyl radical scavenging assays. The free radical scavenging activity was significantly higher in CS-NPs/NAR. MTT based cytotoxic analysis also depicted the non-toxic nature of CS-NPs/NAR towards normal fibroblast 3T3 cells, while cytotoxic effects were noticed against A549 lung cancer cells. Hence, the current investigations showed the superiority of chitosan encapsulated NAR over free NAR and suggested an efficient system for delivering NAR with antioxidant and anticancer activities.