ABSTRACT
BACKGROUND: Acute myeloid leukemia (AML) showed limited clinical therapeutic efficiency with chemotherapy for its multi-distributed lesions and hard-to-kill leukemia cells deep in the bone marrow. RESULTS: Here, a biomimetic nanosystem (DR@PLip) based on platelet membrane (PM) coating and doxorubicin (DOX)/ginsenoside (Rg3) co-loading was developed to potentiate the local-to-systemic chemoimmunotherapy for AML. The PM was designed for long-term circulation and better leukemia cells targeting. The participation of Rg3 was proved to enhance the tumor sensitivity to DOX, thus initiating the anti-tumor immune activation and effectively combating the leukemia cells hiding in the bone marrow. CONCLUSIONS: In conclusion, the strategy that combining immediate chemotherapy with long-term immunotherapy achieved improved therapeutic efficiency and prolonged survival, which provided a new perspective for the clinical treatment of AML.
Subject(s)
Ginsenosides , Leukemia, Myeloid, Acute , Biomimetics , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Ginsenosides/pharmacology , Ginsenosides/therapeutic use , Humans , Immunotherapy , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/pathologyABSTRACT
Leukemia is a hematological malignancy associated with the uncontrolled proliferation of mutant progenitors, suppressing the production of normal blood cells. Current treatments, including chemotherapy, radiotherapy, and immunotherapy, still lead to unsatisfactory results with a 5 year survival rate of only 30-50%. The poor prognosis is related to both disease relapse and treatment-associated toxicity. Delivery strategies can improve the in vivo pharmacokinetics of drugs, navigating the therapeutics to target cells or the tumor microenvironment and reversing drug resistance, which maximizes tumor elimination and alleviates systematic adverse effects. This review discusses available FDA-approved anti-leukemia drugs and therapies with a focus on the advances in the development of anti-leukemia drug delivery systems. Additionally, challenges in clinical translation of the delivery strategies and future research opportunities in leukemia treatment are also included.
Subject(s)
Leukemia , Neoplasms , Drug Delivery Systems/methods , Humans , Immunotherapy/methods , Leukemia/drug therapy , Tumor MicroenvironmentABSTRACT
The aim of this study was to prepare small-molecule camptothecin (CPT) prodrugs and evaluate their effectiveness in colorectal carcinoma therapy. Prodrug nanoparticles (NPs) were physicochemically characterized and evaluated for their cytotoxicity in human colon cancer (HCT116) cell lines. The antitumor efficacy of the NPs was evaluated in HCT116 tumor-bearing mice. The prepared NPs exhibited high drug loading capacity (32% of CPT w/w) and also kept a high active lactone fraction of CPT (>85%) during circulation. The NPs were internalized into tumor cells efficiently compared with free drug and significantly enhanced the drug's therapeutic efficacy. The developed small-molecule CPT prodrug NPs could be a promising strategy in the clinical therapy of colorectal carcinoma.
