PROteolysis TArgeting Chimeras (PROTACs), as a recently identified technique in the field of new drug development, provide new concepts for disease treatment and are expected to revolutionize drug discovery. With high specificity and flexibility, PROTACs serve as an innovative research tool to target and degrade disease-relevant proteins that are not currently pharmaceutically vulnerable to eliminating their functions by hijacking the ubiquitin–proteasome system. To date, PROTACs still face the challenges of low solubility, poor permeability, off-target effects, and metabolic instability. The combination of nanotechnology and PROTACs has been explored to enhance the in vivo performance of PROTACs regarding overcoming these challenging hurdles. In this review, we summarize the latest advancements in the building-block design of PROTAC prodrug nanoparticles and provide an overview of existing/potential delivery systems and loading approaches for PROTAC drugs. Furthermore, we discuss the current status and prospects of the split-and-mix approach for PROTAC drug optimization. Additionally, the advantages and translational potentials of carrier-free nano-PROTACs and their combinational therapeutic effects are highlighted. This review aims to foster a deeper understanding of this rapidly evolving field and facilitate the progress of nano-PROTACs that will continue to push the boundaries of achieving selectivity and controlled release of PROTAC drugs.

Nasopharyngeal carcinoma (NPC) is one of the most common cancers in southern China and the first-line treatment is radiotherapy. Intensity-modulated radiation therapy (IMRT) can deliver high dose to cancer and low dose to normal tissue, but xerostomia is still one of the complications after IMRT. However, how the concentration of saliva electrolytes be affected by IMRT and the effects on the quality of life are still unknown. In this prospective study, 76 NPC patients were recruited from hospitals in Hong Kong to identify the change of saliva electrolytes and xerostomia-related quality of life before and after IMRT. Saliva and questionnaire were collected before IMRT, 1 month, 3 months, 6 months and 12 months after IMRT. The concentration of saliva electrolytes was detected using inductively coupled plasma-optical emission spectroscopy (ICP-OES). Saliva flow rate significantly decreased after IMRT. Decrease in the mean value of pH was observed but the difference is not statistically significant. The concentrations of potassium, iodine, and calcium decreased and chloride concentration increased after IMRT, while the concentrations of sodium, magnesium, copper or zinc were kept at the same level before and after treatment. Xerostomia-related quality of life was adversely affected by IMRT, but partially recovered after 1 year. Our study revealed the change of saliva electrolytes and xerostomia-related quality of life in patients undergone IMRT for NPC.

Hollow hydroxyapatite (HAp) microspheres bearing hierarchical structures have been one of the most popular carriers for drug delivery. However, it's been challenging to find an approach that can simultaneously control the morphology, degradability and drug loading/releasing properties of the microsphere. In this study, hollow mesoporous microspheres composed of nano-sized HAp crystals were hydrothermally synthesized from hollow CaCO₃ precursors prepared via sodium dodecyl sulfate (SDS)-assisted precipitation. The particle size, hollow structure and wall thickness of the fabricated hollow mesoporous carbonated HAp microsphere (CHAM) could be facilely regulated by tailoring the concentration of SDS in the reaction. The achieved carbonate-containing CHAMs were demonstrated to be suitable for drug delivery through either surface attachment or intracellular engulfment without causing cytotoxicity. In addition, their distinguished biodegradability and sustained drug release properties in a pH-dependent manner might allow them to be used in cancer treatment by targeting the acidic microenvironment in a solid tumor. Moreover, the CHAM prepared using SDS at its critical micelle concentration (CMC) was suggested to be optimal for anti-cancer therapy due to its highest entrapment efficiency of cis-diammineplatinum(II) dichloride (CDDP) and the strongest killing effect on human squamous cell carcinoma in vitro.

Periodontal disease, a global health burden linked to dysbiotic oral polymicrobial communities and disrupted immune-inflammatory responses, is critically mediated byPorphyromonas gingivalis(Pg)─the keystone pathogen that sabotages host immunity, triggers tissue inflammation and destruction, and disrupts microbiota balance. Effective therapies should combine antimicrobial action, immune modulation, virulence suppression, and microbiome restoration. Bismuth ions and berberine, which exhibit antimicrobial and epithelial barrier-protecting effects, show potential effectiveness in treating periodontal diseases but face practical limitations due to poor water solubility and bioavailability. To address this, we developed bismuth-doped carbon dots functionalized with structure-modified berberine (BiCD-Ber) as a multifunctional nanomedicine. BiCD-Ber eradicated Pg in various forms, restored Pg-perturbed immune responses in gingival fibroblasts, and preserved epithelial barrier integrity. The doped bismuth ions neutralized Pg virulence factors by blocking the catalytic sites of gingipains. To facilitate in vivo delivery, BiCD-Ber was encapsulated in a disulfide-modified hyaluronic acid hydrogel that degrades in response to Pg metabolites. This BiCD-Ber hydrogel system modulated subgingival microbiota, alleviated inflammation in gingiva, and thereby prevented alveolar bone loss. This approach to concurrently eliminating Pg, modulating inflammatory responses , suppressing virulence factors, and restoring microbiota showcases great potential in managing periodontitis effectively.