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Combinatory Delivery of Etoposide and siCD47 in a Lipid Polymer Hybrid Delays Lung Tumor Growth in an Experimental Melanoma Lung Metastatic Model
Author(s) -
AbdelBar Hend Mohamed,
Walters Adam A.,
Wang Julie TzuWen,
AlJamal Khuloud T.
Publication year - 2021
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202001853
Subject(s) - biodistribution , in vivo , etoposide , cancer research , cytotoxicity , transfection , lung cancer , chemistry , lung , small interfering rna , liposome , in vitro , pharmacology , medicine , materials science , chemotherapy , biology , pathology , biochemistry , microbiology and biotechnology , gene
This study investigated the feasibility of lipid polymer hybrid nanoparticles (LPH) as a platform for the combinatorial delivery of small interfering RNA (siRNA) and etoposide (Eto). Different Eto loaded LPH formulations (LPH Eto ) are prepared. The optimized cationic LPH Eto with a particle size of 109.66 ± 5.17 nm and Eto entrapment efficiency (EE %) of 80.33 ± 2.55 is used to incorporate siRNA targeting CD47 (siCD47), a do not eat me marker on the surface of cancer cells. The siRNA‐encapsulating LPH (LPH siNEG‐Eto ) has a particle size of 115.9 ± 4.11 nm and siRNA EE % of 63.54 ± 4.36 %. LPHs improved the cellular uptake of siRNA in a dose‐ and concentration‐dependent manner. Enhanced cytotoxicity (3.8‐fold higher than Eto solution) and high siRNA transfection efficiency (≈50 %) are obtained. An in vivo biodistribution study showed a preferential uptake of the nanosystem into lung, liver, and spleen. In an experimental pseudo‐metastatic B16F10 lung tumor model, a superior therapeutic outcome can be observed in mice treated with combinatory therapy. Immunological studies revealed elevated CD4+, CD8+ cells, and macrophages in the lung following combinatory treatment. The study suggests the potential of the current system for combinatory chemotherapy and immunotherapy for the treatment of lung cancer or lung metastasis.