Advanced Therapeutics最新文献

Oxaliplatin-based chemotherapy combined with PD-1 antibody has become the standard treatment for advanced or metastatic gastric cancer. However, the neurotoxicity of oxaliplatin limits its long-term use. A total of 84 patients who received oxaliplatin-based chemotherapy plus PD-1 antibody are enrolled in this study, among which 44 patients are maintained with capecitabine plus PD-1 antibody, whereas the other 40 patients are maintained with capecitabine monotherapy. The primary endpoint is progression-free survival (PFS) and the secondary endpoint is overall-survival (OS). Subgroup analysis is performed based on expression of PD-L1 and CXCL12. The median PFS is significantly longer in capecitabine plus PD-1 antibody group (n = 44) than that in capecitabine monotherapy (n = 40) group. The median OS is significantly longer in capecitabine plus PD-1 antibody group than that in capecitabine monotherapy group. Subgroup analysis showed that patients with high expression of PD-L1 or low level of CXCL12 benefited more significantly from capecitabine plus PD-1 antibody maintenance. Maintenance therapy with capecitabine plus PD-1 antibody significantly prolongs the PFS and OS in patients without disease progression after first-line treatment. Patients with high expression of PD-L1 or low expression of CXCL12 benefit more significantly from maintenance therapy.

Despite advancements in the treatment of glioblastoma, it faces challenges due to tumor heterogeneity, the blood-brain barrier, recurrence, immune evasion, and conventional strategies, leading to low survival and a poor prognosis. Therefore, it is crucial to develop novel, useful treatment strategies for improving brain distribution to overcome blood-brain barriers (BBB) and help the treatment of glioblastoma. Conventional immunotherapy like checkpoint inhibitors, CAR-T cell therapy, monoclonal antibodies, cancer vaccines, and adoptive cell transfer often suffers from low therapeutic outcomes because the singular therapy generally has shortcomings, such as the cold immune microenvironment of brain tumors. In contrast, the emerging combinatory immunotherapy integrated with chemo-immunotherapy, photothermal-immunotherapy, and radio-immunotherapy has shown great promise to modulate tumoral immune microenvironment and boost treatment outcomes. This review discusses the immune microenvironment of GBM, its impact on immunological effects, current immunotherapy methods, and advanced studies. It also introduces combinational GBM immunotherapy with traditional cancer therapies like chemo-immunotherapy, surgery-immunotherapy, photothermal-immunotherapy, and radiotherapy-immunotherapy. In the future, it is anticipated that this article will provide beneficial information and a path for the strategy of innovative, efficient combination immunotherapy in the treatment of glioblastoma.

Photodynamic therapy, a noninvasive cancer treatment strategy, is a promising remedy for malignant skin cancers. However, treatment of skin cancer with this method requires sufficient photosensitizer molecules to permeate into cancer cells before illumination for effective activation to induce potent reactive oxygen species for eliminating cancer cells. However, transdermal drug delivery using conventional photosensitizers faces major challenges due to skin barriers, diminishing the effectiveness of drug penetration and therapeutic efficacies. To overcome these limitations, biocompatible, physiologically dissolvable, and optically activatable functional microneedle devices are applied for effective percutaneous penetration of drug molecules into solid tumors in a murine model. The proposed wireless light-emitting diode light-driven functional microneedle device that effectively induces apoptosis of cancer cells and disruption of the tumor area and can enhance in vitro, ex vivo, and in vivo drug-delivery effectiveness for treating skin cancer. The design and strategy of the present functional microneedle devices can help shed light on future advanced cancer therapy.

Drug delivery to mucosal tissues presents considerable challenges related to the complex nature of the mucus layer protecting such tissues. This aggravates when delivering hydrophobic drugs, often requiring incorporation of drugs to nanoparticles and use of mucoadhesive systems. This paper aimed to develop an antifungal chitosan (CHI)-based film loading itraconazole (ITZ) nanocrystals (NCs) with precisely controlled surface charge for enhanced mucoadhesion. Cationic and anionic ITZ NCs are prepared using wet media milling with mean particle sizes and zeta potentials of 226.9 ± 1.4 nm and 234.0 ± 2.90 nm, and +15.4 ± 2.8 mV and −16.2 ± 1.3 mV, for the cationic and anionic NCs, respectively. Cationic ITZ-NCs exhibits a higher affinity to mucin particles. NCs-loaded films showed stronger mechanical properties and adhesiveness compared with ITZ powder-loaded films. Physicochemical analysis reveals that crystalline properties of the ITZ are preserved, with no drug-excipients interaction. A significantly higher amount of ITZ mucosal deposition is obtained from films containing NCs (1360.23 ± 718.73 µg cm⁻²) compared with that from films containing ITZ powder (58.83 ± 37.45 µg cm⁻²). This work demonstrates the feasibility of tailoring the NCs surface, with the resultant systems showing potential for the management of fungal infections in mucosal tissues.

GLP-1 RAs are effective therapies for obesity which affects 70% of American adults. However, frequent subcutaneous injections pose challenges for patients and the environment. Here, a programmable scheduled microneedle system is introduced, delivering Semaglutide instantaneously and longitudinally over a month with one skin patch administration. This sustains the drug efficacy and addresses common issues of traditional administration using multiple injections such as pain, needle phobia, high cost and the need of medical personnel, ensuring effective obesity management. More details can be found in article 2400028 by Thanh Duc Nguyen and co-workers.

Zeolitic imidazolate frameworks (ZIFs) are emerging as a promising nanocarrier platform for drug delivery. In article 2300447, Yongheng Zhu, Xinghua Gao, Yuan Zhang, and co-workers elucidate the crucial role of surface charge and Lewis-base ligand in determining cytotoxicity, cellular uptake, and intracellular release. These findings offer valuable insights for the screening of ZIF-based nanocarriers.

Despite extensive advances in cancer research, glioblastoma (GBM) still remains a very locally invasive and thus challenging tumor to treat, with a poor median survival. Tumor cells remodel their microenvironment and utilize extracellular matrix to promote invasion and therapeutic resistance. It is aimed here to determine how GBM cells exploit hyaluronan (HA) to maintain proliferation using ligand-receptor dependent and ligand-receptor independent signaling. Tissue engineering approaches are used to recreate the 3D tumor microenvironment in vitro, then analyze shifts in metabolism, hyaluronan secretion, HA molecular weight distribution, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient-derived xenograft GBM cells. It is revealed that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype-dependent manner. A tumor-specific combination treatment of HYAL and HAS inhibitors is proposed to disrupt the HA stabilizing role in GBM cells. Taken together, these data shed light on the dual metabolic and ligand – dependent signaling roles of hyaluronan in glioblastoma.