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Periodontitis is a chronic inflammatory condition driven by plaque-associated microorganisms, where uncontrolled bacterial invasion and proliferation impair host immune responses, leading to localized periodontal tissue inflammation and bone destruction. Conventional periodontal therapies face challenges, including incomplete microbial clearance and the rise of antibiotic resistance, limiting their precision and effectiveness in managing periodontitis. Recently, nanotherapies based on polymeric materials have introduced advanced approaches to periodontal antimicrobial therapy through diverse antimicrobial mechanisms. This review explored specific mechanisms, emphasizing the design of polymer-based agents that employ individual or synergistic antimicrobial actions, and evaluated the innovations and limitations of current strategies while forecasting future trends in antimicrobial development for periodontitis. [ABSTRACT FROM AUTHOR]

Antibody drug conjugates (ADCs) have made impressive strides in the clinic in recent years with 11 Food and Drug Administration approvals, including 6 for the treatment of patients with solid tumors. Despite this success, the development of new agents remains challenging with a high failure rate in the clinic. Here, we show that current approved ADCs for the treatment of patients with solid tumors can all show substantial efficacy in some mouse models when administered at a similar weight-based [milligrams per kilogram (mg/kg)] dosing in mice that is tolerated in the clinic. Mechanistically, equivalent mg/kg dosing results in a similar drug concentration in the tumor and a similar tissue penetration into the tumor due to the unique delivery features of ADCs. Combined with computational approaches, which can account for the complex distribution within the tumor microenvironment, these scaling concepts may aid in the evaluation of new agents and help design therapeutics with maximum clinical efficacy.

Antibody-drug conjugates (ADCs) have experienced a surge in clinical approvals in the past five years. Despite this success, a major limitation to ADC efficacy in solid tumors is poor tumor penetration, which leaves many cancer cells untargeted. Increasing antibody doses or co-administering ADC with an unconjugated antibody can improve tumor penetration and increase efficacy when target receptor expression is high. However, it can also reduce efficacy in low-expression tumors where ADC delivery is limited by cellular uptake. This creates an intrinsic problem because many patients express different levels of target between tumors and even within the same tumor. Here, we generated High-Avidity, Low-Affinity (HALA) antibodies that can automatically tune the cellular ADC delivery to match the local expression level. Using HER2 ADCs as a model, HALA antibodies were identified with the desired HER2 expression-dependent competitive binding with ADCs in vitro . Multi-scale distribution of trastuzumab emtansine and trastuzumab deruxtecan co-administered with the HALA antibody were analyzed in vivo , revealing that the HALA antibody increased ADC tumor penetration in high-expression systems with minimal reduction in ADC uptake in low-expression tumors. This translated to greater ADC efficacy in immunodeficient mouse models across a range of HER2 expression levels. Furthermore, Fc-enhanced HALA antibodies showed improved Fc-effector function at both high and low expression levels and elicited a strong response in an immunocompetent mouse model. These results demonstrate that HALA antibodies can expand treatment ranges beyond high expression targets and leverage strong immune responses., Competing Interests: Conflicts of Interest P.M.T. is a member of the scientific advisory boards for Nabla Bio, Adimab, Aureka Biotechnologies, and Dualitas Therapeutics. G.M.T. has served on the scientific advisory boards of AstraZeneca/Medimmune, Advanced Proteome Therapeutics, Catalent, Merck, Mersana, and Neoleukin. The authors have intellectual property related to the use of affinity-modulated antibodies for use with ADCs.

The rapid development of scaffold-based bone tissue engineering strongly relies on the fabrication of advanced scaffolds and the use of newly discovered functional drugs. As the creation of new drugs and their clinical approval often cost a long time and billions of U.S. dollars, producing scaffolds loaded with repositioned conventional drugs whose biosafety has been verified clinically to treat critical-sized bone defect has gained increasing attention. Carfilzomib (CFZ), an approved clinical proteasome inhibitor with a much fewer side effects, is used to replace bortezomib to treat multiple myeloma. It is also reported that CFZ could enhance the activity of alkaline phosphatase and increase the expression of osteogenic transcription factors. With the above consideration, in this study, a porous CFZ/β-tricalcium phosphate/poly lactic-co-glycolic acid scaffold (designated as "cytidine triphosphate [CTP]") was produced through cryogenic three-dimensional (3D) printing. The hierarchically porous CTP scaffolds were mechanically similar to human cancellous bone and can provide a sustained CFZ release. The implantation of CTP scaffolds into critical-sized rabbit radius bone defects improved the growth of new blood vessels and significantly promoted new bone formation. To the best of our knowledge, this is the first work that shows that CFZ-loaded scaffolds could treat nonunion of bone defect by promoting osteogenesis and angiogenesis while inhibiting osteoclastogenesis, through the activation of the Wnt/β-catenin signaling. Our results suggest that the loading of repositioned drugs with effective osteogenesis capability in advanced bone tissue engineering scaffold is a promising way to treat critical-sized defects of a long bone., Competing Interests: The authors have no conflict of interest to declare., (Copyright: © 2021 Li, et al.)