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Design of Hybrid MnO 2 ‐Polymer‐Lipid Nanoparticles with Tunable Oxygen Generation Rates and Tumor Accumulation for Cancer Treatment
Author(s) -
Gordijo Claudia R.,
Abbasi Azhar Z.,
Amini Mohammad Ali,
Lip Ho Yin,
Maeda Azusa,
Cai Ping,
O'Brien Peter J.,
DaCosta Ralph S.,
Rauth Andrew M.,
Wu Xiao Yu
Publication year - 2015
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201404511
Subject(s) - biocompatibility , materials science , tumor hypoxia , tumor microenvironment , nanoparticle , in vivo , biophysics , polymer , polyelectrolyte , hypoxia (environmental) , oxygen , nanotechnology , cancer research , chemistry , tumor cells , organic chemistry , medicine , biology , microbiology and biotechnology , metallurgy , radiation therapy , composite material
Manganese dioxide (MnO 2 ) nanoparticles (NPs) were discovered in previous work to be effective in improving tumor oxygenation (hypoxia) and reducing H 2 O 2 and acidity in the tumor microenvironment (TME) via local injection. To develop MnO 2 formulations useful for clinical application, hybrid NPs are designed with tailored hydrophobicity and structure suitable for intravenous injection, with good blood circulation, biocompatibility, high tumor accumulation, and programmable oxygen generation rate. Two different hybrid NPs are constructed by embedding polyelectrolyte‐MnO 2 (PMD) in hydrophilic terpolymer/protein‐MnO 2 (TMD) or hydrophobic polymer/lipid‐MnO 2 (LMD) matrices. The in vitro reactivity of the MnO 2 toward H 2 O 2 is controlled by matrix material and NP structure and dependent on pH with up to two‐fold higher O 2 generation rate at acidic (tumor) pH than at systemic pH. The hybrid NPs are found to be safe to cells in vitro and organs in vivo and effectively decrease tumor hypoxia and hypoxia‐inducible‐factor‐1alpha through local or systemic administration. Fast acting TMD reduces tumor hypoxia by 70% in 0.5 h by local injection. Slow acting LMD exhibits superior tumor accumulation and retention through the systemic administration and decreased hypoxia by 45%. These findings encourage a broader use of hybrid MD NPs to overcome TME factors for cancer treatment.