Application of Bone-Targeted Nanoparticles for Trilaciclib Delivery in Chemotherapy-Induced Myelosuppression

Myelosuppression that occurs as a result of chemotherapy is a serious problem that needed to be overcome in the treatment of cancer. Myelosuppression can cause anemia, neutropenia and thrombocytopenia[1]. Trilaciclib is an FDA approved CDK4/6 inhibitor that have the ability to induce transient G1 phase arrest in hematopoietic stem cells, which reduces chemotherapy induced damage and toxicity.[2] Yet, systemic treatment of Trilaciclib can lead to off-target effects.In this paper we are discussing the application of an already existing delivery system which targets bones, PLGA-PEG nanoparticles functionalized with Alendronate, this enhances the targeted delivery of Trilaciclib in bone marrow as alendronate has a high affinity towards bone hydroxyapatite.[3] This will increase the specificity of the drug and reduce systemic toxicity and side effects. Even with these advantages, there is a significant disadvantage with this combination of a bisphosphonate and a CDK inhibitor and that's is medication-related osteonecrosis of the jaw (MRONJ).[4] This paper evaluates the feasibility, limitations, and potential impact of this approach in improving chemotherapy outcomes, based on existing nanoparticle research.