Nanotherapeutics for multiple myeloma.

Multiple myeloma (MM) is an age-related hematological malignancy with an estimated 30,000 new cases and 13,000 deaths per year. A disease of antibody-secreting malignant plasma B-cells that grow primarily in the bone marrow (BM), MM causes debilitating fractures, anemia, renal failure, and hypercalcemia. In addition to the abnormal genetic profile of MM cells, the permissive BM microenvironment (BMM) supports MM pathogenesis. Although advances in treatment options have significantly enhanced survival in MM patients, transient perfusion of small-molecule drugs in the BM does not provide sufficient residence to enhance MM cell-drug interaction, thus allowing some myeloma cells to escape the first line of treatment. As such, there remains a crucial need to develop advanced drug delivery systems that can navigate the complex BMM and effectively reach the myeloma cells. The high vascular density and spongy nature of bone structure suggest that nanoparticles (NPs) can serve as smart drug-delivery systems capable of extravasation and retention in various BM compartments to exert a durable therapeutic effect. In this focus article, we first summarize the pathophysiology of MM, emphasizing how the BM niche presents serious challenges for effective treatment of MM with small-molecule drugs. We then pivot to current efforts to develop NP-based drug carriers and intrinsically therapeutic nanotherapeutics. The article concludes with a brief perspective on the opportunities and challenges in developing and translating nanotherapeutics to improve the treatment outcomes of MM patients. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.