The Wang laboratory has an extensive research portfolio focusing primarily on developing nanomedicine for inflammatory, autoimmune and musculoskeletal diseases. In addition to the successful utility of nanomedicine in the oncology arena, we believe there are rich opportunities for nanomedicine application in the new disease areas, which would necessitate in-depth understandings of the interaction between the pathophysiology and the nanomedicine. It would also necessitate novel designs of nanomedicine to meet the unique needs of non-oncological conditions.
Enhanced Permeability and Retention (EPR) effect is the pathological feature that governs the passive targeting of nanomedicine to solid tumor. Based on our early work on polymeric prodrug for rheumatoid arthritis, we have established that nanomedicine would passively target inflammation through effective extravasation at the inflammatory lesion and the swift internalization and subcellular processing by inflammatory infiltrates and activated resident cells. This novel mechanism of nanomedicine targeting to inflammation was defined as Extravasation through Leaky Vasculature and Inflammatory cell-mediated Sequestration (ELVIS), which is distinctively different from EPR effect. Based on ELVIS mechanism, we have developed multiple polymeric prodrugs nanomedicine of glucocorticoids, statins, opioids and Janus kinase (JAK) inhibitors. Their improved therapeutic efficacy and superior safety profiles have been validated in preclinical models of diverse spectrum of inflammatory/autoimmune diseases, including rheumatoid arthritis (RA), lupus nephritis (LN), aseptic orthopaedic implant loosening, delayed fracture healing, inflammatory bowel disease (IBD), trauma brain injury (TBI), focal segmental glomerulosclerosis (FSGS), spinal cord injury (SCI), and cytokine storm.
Our laboratory also interests in the development of osteotropic prodrug nanomedicine for musculoskeletal conditions. To achieve hard tissue tropism in vivo, we have use acidic peptides and bisphosphonates as bone-targeting moiety. To overcome the potential complications associated with the use of bisphosphonates, we pioneered the use of biodegradable pyrophosphate as a novel targeting moiety. In collaboration with cancer biologists, we have developed bone-targeted polymeric prodrug nanomedicine of docetaxol and TPCK (cathepsin G inhibitor) for treatment of cancer bone metastasis. In addition, we have also developed bone-targeting liposome, polyrotaxane, micelles and thermoresponsive hydrogels as delivery vehicles of bone anabolic agents (e.g., Statins, GSK inhibitor, Sclerostin antibody, Salvianic acid A, Tanshinone, etc.) for improved treatment of delayed fracture healing and periodontal bone erosion. Most recently, we also developed a novel prodrug hydrogel delivery system for the improved treatment of osteoarthritis pain.
As an off shoot of the osteotropic nanomedicine program, we have pioneered the dentotropic delivery concept. Given the high hydroxyapatite content in dental enamel, we realized that the osteotropic systems developed for skeletal disorders could also be dentotropic. But is there a need to deliver functional agents to the dental surfaces? It turns out that most of the work on drug or functional agents’ delivery into the oral cavity has been overwhelmingly focused on mucus adhesive delivery. While significant achievements have been made, the specific delivery of drug/functional agents to the tooth surface has not been explored. Furthermore, constant renewing nature of the oral mucosa layer determines that the mucus adhesive technologies have its inherent limitation in term of retaining compounds in the oral cavity, especially on the tooth surface. To address this limitation, we designed and developed a dentotropic Pluronic micelle system by conjugating tooth-binding pyrophosphate to the chain termini of Pluronics. Using the modified Pluronics as excipients, we have developed prototype antimicrobial-containing mouthrinse and toothpaste, which were found with superior efficacy than non-targeted antimicrobial.