Combinatory Delivery of Etoposide and siCD47 in a Lipid Polymer Hybrid Delays Lung Tumor Growth in an Experimental Melanoma Lung Metastatic Model

Abstract

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.

Elimination of Cancer Cells in Co-Culture: Role of Different Nanocarriers in Regulation of CD47 and Calreticulin-Induced Phagocytosis

“…Others used different types of LNPs conjugated with CD47_siRNA in lung and colon cancers. These studies reported knockdown efficiency values of CD47 between 65 and 80%. , The cytotoxicity of LNPs used here was studied on all cell lines. Results showed high viability (more than 90%) at the concentration used here in cancer and normal cells (Figure S4).…”

Lipid polymer hybrid nanocarriers as a combinatory platform for different anti-SARS-CoV-2 drugs supported by computational studies

“…Different LPH NPs formulations co-loaded with azithromycin and piroxicam (LPH Azi–Pir ) or niclosamide and piroxicam (LPH Nic–Pir ) were prepared by a single-step nanoprecipitation self-assembly technique. 42 Briefly, PLGA (5 mg mL −1 ), piroxicam (0.75 mg mL −1 ) and azithromycin (0.75 mg mL −1 ) or niclosamide (0.75 mg mL −1 ) were dissolved in DMF (1 mL) to form the organic phase. The aqueous phase was prepared by dissolving lecithin (0.5 mg mL −1 ), DSPE-PEG 2000 (0.5 mg mL −1 ) and Tween® 80 (10 mg mL −1 ) in 4% v/v hydroalcoholic solution (9 mL) at 70 °C for 15 min to ensure the complete desolvation of the lipid.…”

Recent Advances of Tumor Therapy Based on the CD47-SIRPα Axis

“…Al-Jamal and co-workers encapsulated CD47 siRNA and chemotherapeutic drug etoposide in the core of PLGA, and lipids such as lecithin encapsulated it to form LPH, which can protect siRNA from serum and RNase degradation. Meanwhile, the expression of CD47 in melanoma B16 cells was reduced by 50–60%, and the lung metastasis was significantly inhibited in vivo . In summary, with the use of lipids or polymers to protect nucleic acid drugs and the use of the EPR effect of the carrier to penetrate into tumor tissue, the internalized siRNA can effectively reduce the expression of CD47 in tumor cells and inhibit tumor progression.…”

“…Meanwhile, the expression of CD47 in melanoma B16 cells was reduced by 50−60%, and the lung metastasis was significantly inhibited in vivo. 121 In summary, with the use of lipids or polymers to protect nucleic acid drugs and the use of the EPR effect of the carrier to penetrate into tumor tissue, the internalized siRNA can 122 To further improve the targeting of these vectors and reduce "off-tumor" effects, aCD47 is used to promote the delivery of nanoparticles and also exert antitumor function or tumor imaging.…”