Peptide–drug conjugates (PDCs) have emerged as a next-generation therapeutic platform, combining the target specificity of peptides with the pharmacological potency of small-molecule drugs. As an evolution beyond antibody–drug conjugates (ADCs), PDCs offer distinct advantages, including enhanced cellular permeability, improved drug selectivity, and versatile design flexibility. This review provides a comprehensive analysis of the fundamental components of PDCs, including homing peptide selection, linker engineering, and payload optimization, alongside strategies to address their inherent challenges, such as stability, bioactivity, and clinical translation barriers. Therapeutic applications of PDCs span oncology, infectious diseases, metabolic disorders, and emerging areas like COVID-19, with several conjugates advancing in clinical trials and achieving regulatory milestones. Innovations, including bicyclic peptides, supramolecular architectures, and novel linker technologies, are explored as promising avenues to enhance PDC design. Additionally, this review examines the clinical trajectory of PDCs, emphasizing their therapeutic potential and highlighting ongoing trials that exemplify their efficacy. By addressing limitations and leveraging emerging advancements, PDCs hold immense promise as targeted therapeutics capable of addressing complex disease states and driving progress in precision medicine.

Peptide-drug conjugates (PDCs) have emerged as a next-generation therapeutic platform, combining the target specificity of peptides with the pharmacological potency of small-molecule drugs. As an evolution beyond antibody-drug conjugates (ADCs), PDCs offer distinct advantages, including enhanced cellular permeability, improved drug selectivity, and versatile design flexibility. This review provides a comprehensive analysis of the fundamental components of PDCs, including homing peptide selection, linker engineering, and payload optimization, alongside strategies to address their inherent challenges, such as stability, bioactivity, and clinical translation barriers. Therapeutic applications of PDCs span oncology, infectious diseases, metabolic disorders, and emerging areas like COVID-19, with several conjugates advancing in clinical trials and achieving regulatory milestones. Innovations, including bicyclic peptides, supramolecular architectures, and novel linker technologies, are explored as promising avenues to enhance PDC design. Additionally, this review examines the clinical trajectory of PDCs, emphasizing their therapeutic potential and highlighting ongoing trials that exemplify their efficacy. By addressing limitations and leveraging emerging advancements, PDCs hold immense promise as targeted therapeutics capable of addressing complex disease states and driving progress in precision medicine

Exosomes are nanoscale vesicles derived from cell membranes with crucial roles in physiological and disease-specific processes. EVs may offer biological compatibility and cell-interactive surfaces, but these properties are source-, process-, cargo-, and route-dependent and should not be assumed to be superior to liposomes or other synthetic carriers. These unique properties make exosomes highly attractive platforms for drug delivery, diagnostics, and therapeutic applications, as they combine natural stability with functional versatility in cellular communication and disease modulation. This review consolidates current advances in exosome biology, including their biogenesis, isolation, characterization, and engineering for antimicrobial applications. Commonly used isolation methods for exosomes include ultra-centrifugation, chromatography, immune-affinity capture, ultrafiltration, and polymeric precipitation, with newer microfluidic-based techniques also being explored. Strategies for drug incorporation are classified into passive methods (e.g., incubation and diffusion) and active techniques (including electroporation, sonication, extrusion, chimeric modification, and endogenous loading). EV-based systems may help address selected antimicrobial resistance (AMR) challenges by enabling delivery of antibiotics, antimicrobial peptides, and biologics, thereby improving their stability and site-specific activity. In addition to their role as drug carriers, exosomes can influence immune responses through antigen presentation and activate immune cells, including dendritic cells, macrophages, and T lymphocytes. Despite their many potential advantages and trade-offs, exosomes still face several hurdles that limit their broad clinical application, including suboptimal drug-loading efficiency, rapid systemic clearance, variability between production batches, and challenges in large-scale manufacturing. Nonetheless, exosomes are increasingly recognized as a versatile nanomedicine platform with dual functionality for site-specific drug delivery and immunotherapy. They can transport diverse therapeutic molecules while maintaining high biocompatibility, highlighting their potential in addressing AMR. To advance clinical translation, further efforts are required to optimize loading strategies, establish scalable production systems, and ensure comprehensive safety evaluation. Leveraging exosome-based systems for antimicrobial and biologic delivery may open new avenues for addressing the global burden of antimicrobial resistance and advancing precision nanomedicine.