Cytarabine nanotherapeutics with increased stability and enhanced lymphoma uptake for tailored highly effective therapy of mantle cell lymphoma
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
33186784
DOI
10.1016/j.actbio.2020.11.014
PII: S1742-7061(20)30657-7
Knihovny.cz E-resources
- Keywords
- Cytarabine, Drug delivery, HPMA copolymer, Mantle cell lymphoma, Nanotherapeutics, Patient-derived xenograft (PDX),
- MeSH
- Cytarabine pharmacology MeSH
- Adult MeSH
- Humans MeSH
- Neoplasm Recurrence, Local MeSH
- Lymphoma, Mantle-Cell * drug therapy MeSH
- Antineoplastic Combined Chemotherapy Protocols MeSH
- Rituximab therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Cytarabine MeSH
- Rituximab MeSH
Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma (B-NHL) with chronically relapsing clinical course. Implementation of cytarabine (araC) into induction and salvage regimen became standard of care for majority of MCL patients. In this study, tailored N-(2-hydroxypropyl)methacrylamide (HPMA)-based polymer nanotherapeutics containing covalently bound araC (araC co-polymers) were designed, synthesized and evaluated for their anti-lymphoma efficacy in vivo using a panel of six patient-derived lymphoma xenografts (PDX) derived from newly diagnosed and relapsed / refractory (R/R) MCL. While free araC led to temporary inhibition of growth of MCL tumors, araC co-polymers induced long-term disappearance of the engrafted lymphomas with no observed toxicity even in the case of PDX models derived from patients, who relapsed after high-dose araC-based treatments. The results provide sound preclinical rationale for the use of HPMA-based araC co-polymers in induction, salvage or palliative therapy of MCL patients.
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