Nanoparticle delivery systems, general approaches, and their implementation in multiple myeloma

Abstract

Multiple myeloma (MM) is a hematological malignancy that remains incurable, with relapse rates greater than 90%. The main limiting factor for the effective use of chemotherapies in MM is the serious side effects caused by these drugs. The emphasis in cancer treatment has shifted from cytotoxic, non-specific chemotherapies to molecularly targeted and rationally designed therapies showing greater efficacy and fewer side effects. Traditional chemotherapy has shown several disadvantages such as lack of targeting capabilities, systemic toxicity and side effects; low therapeutic index, as well as, most anticancer drugs have poor water solubility. Nanoparticle delivery systems (NPs) are capable of targeting large doses of chemotherapies into the target area while sparing healthy tissues, overcoming the limitations of traditional chemotherapy. Here, we review the current state-of-the-art in nanoparticle-based strategies designed to treat multiple myeloma. Many nanoparticle delivery systems have been studied for myeloma using non-targeted NPs (liposomes, polymeric NPs, and inorganic NPs), triggered NPs, as well as targeted NPs (VLA-4, ABC drug transporters, bone microenvironment targeting). The results in preclinical and clinical studies are promising; however, there remains much to be learned in the emerging field of nanomedicine in myeloma.

Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma

“…One potential approach to improve the efficacy and reduce the toxicity of treatment is to encapsulate the PI in a nanoparticle and add targeting elements which will increase the specific accumulation of the particle (and the PI within) to the tumor 13,19 . We previously demonstrated that BTZ loaded into a chitosan nanoparticle and decorated with anti-CD38 antibodies improved the accumulation of BTZ in MM cells, which overexpress CD38, and reduced the toxicity of BTZ in normal tissue 14 .…”

Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma

“…NPs drug delivery systems allow the delivery of larger doses of chemotherapies and increase the drug bioavailability into targeted areas, thus sparing healthy tissues [13]. Chitosan has been widely used in drug delivery systems.…”

“…However, this liposomal formulation showed reduced cytotoxic effects in MM cells compared to free BTZ, attributed to the kinetics of BTZ release from their NPs. Moreover, these particles were relying on passive targeting to the tumor through enhanced permeability and retention (EPR) effect, which is the tendency for NPs and other molecular agents to conglomerate more in tumor versus normal tissue [13-15]. But in addition to the unspecific nature of the EPR effect, large tumors may not display the EPR effect, thus causing for fewer NPs to accumulate in the central areas [16].…”

Targeted Approaches to Inhibit Sialylation of Multiple Myeloma in the Bone Marrow Microenvironment

“…Nanomedicine approaches offer the potential of enhanced and more personalized therapeutics in MM with a reduced risk of off-target effects (Table 1). Current treatments in MM rely on immunomodulatory drugs such as lenalidomide combined with proteasome inhibitors (PI) such as bortezomib (De La Puente and Azab, 2017). The introduction of PI inhibitors has contributed to major improvements in patient survival, but off-target effects, in particular neurotoxicity, remain a major concern (Richardson et al, 2009).…”