Polymeric nanomedicines targeting hematological malignancies.

ABSTRACT

Hematological malignancies (HMs) typically persisting in the blood, lymphoma, and/or bone marrow invalidate surgery and local treatments clinically used for solid tumors. The presence and drug resistance nature of cancer stem cells (CSCs) further lends HMs hard to cure. The development of new treatments like molecular targeted drugs and antibodies has improved the clinical outcomes for HMs but only to a certain extent, due to issues of low bioavailability, moderate response, occurrence of drug resistance, and/or dose-limiting toxicities. In the past years, polymeric nanomedicines targeting HMs including refractory and relapsed lymphoma, leukemia and multiple myeloma have emerged as a promising chemotherapeutic approach that is shown capable of overcoming drug resistance, delivering drugs not only to cancer cells but also CSCs, and increasing therapeutic index by lessening drug-associated adverse effects. In addition, polymeric nanomedicines have shown to potentiate next-generation anticancer modalities such as therapeutic proteins and nucleic acids in effectively treating HMs. In this review, we highlight recent advance in targeted polymeric nanoformulations that are coated with varying ligands (e.g. cancer cell membrane proteins, antibodies, transferrin, hyaluronic acid, aptamer, peptide, and folate) and loaded with different therapeutic agents (e.g. chemotherapeutics, molecular targeted drugs, therapeutic antibodies, nucleic acid drugs, and apoptotic proteins) for directing to distinct targets (e.g. CD19, CD20, CD22, CD30, CD38, CD44, CD64, CXCR, FLT3, VLA-4, and bone marrow microenvironment) in HMs. The advantages and potential challenges of different designs are discussed.