TY - JOUR
T1 - Surface Immobilization of Anti-VEGF Peptide on SPIONs for Antiangiogenic and Targeted Delivery of Paclitaxel in Non-Small-Cell Lung Carcinoma
AU - Ngema, Lindokuhle M.
AU - Adeyemi, Samson A.
AU - Marimuthu, Thashree
AU - Ubanako, Philemon N.
AU - Ngwa, Wilfred
AU - Choonara, Yahya E.
N1 - Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.
PY - 2023/7/17
Y1 - 2023/7/17
N2 - A design has been established for the surface decoration of superparamagnetic iron oxide nanoparticles (SPIONs) with anti-vascular endothelial growth factor peptide, HRH, to formulate a targeted paclitaxel (PTX) delivery nanosystem with notable tumor targetability and antiangiogenic activity. The design methodology included (i) tandem surface functionalization via coupling reactions, (ii) pertinent physicochemical characterization, (iii) in vitro assessment of drug release, anti-proliferative activity, and quantification of vascular endothelial growth factor A (VEGF-A) levels, and (iv) in vivo testing using a lung tumor xenograft mouse model. Formulated CLA-coated PTX-SPIONs@HRH depicted a size and surface charge of 108.5 ± 3.5 nm and −30.4 ± 2.3 mV, respectively, and a quasi-spherical shape relative to pristine SPIONs. Fourier transform infrared (FTIR) analysis and estimation of free carboxylic groups supported the preparation of the CLA-coated PTX-SPIONs@HRH. CLA-coated PTX-SPIONs@HRH exhibited high PTX loading efficiency (98.5%) and sustained release in vitro, with a marked dose dependent anti-proliferative activity in A549 lung adenocarcinoma cells, complimented by an enhanced cellular uptake. CLA-coated PTX-SPIONs@HRH significantly reduced secretion levels of VEGF-A in human dermal microvascular endothelial cells from 46.9 to 35.6 pg/mL compared to untreated control. A 76.6% tumor regression was recorded in a lung tumor xenograft mouse model following intervention with CLA-coated PTX-SPIONs@HRH, demonstrating tumor targetability and angiogenesis inhibition. CLA-coated PTX-SPIONs@HRH enhanced the half-life of PTX by almost 2-folds and demonstrated a prolonged PTX plasma circulation time from a subcutaneous injection (SC). Thus, it is suggested that CLA-coated PTX-SPIONs@HRH could provide a potential effective treatment modality for non-small-cell lung carcinoma as a nanomedicine.
AB - A design has been established for the surface decoration of superparamagnetic iron oxide nanoparticles (SPIONs) with anti-vascular endothelial growth factor peptide, HRH, to formulate a targeted paclitaxel (PTX) delivery nanosystem with notable tumor targetability and antiangiogenic activity. The design methodology included (i) tandem surface functionalization via coupling reactions, (ii) pertinent physicochemical characterization, (iii) in vitro assessment of drug release, anti-proliferative activity, and quantification of vascular endothelial growth factor A (VEGF-A) levels, and (iv) in vivo testing using a lung tumor xenograft mouse model. Formulated CLA-coated PTX-SPIONs@HRH depicted a size and surface charge of 108.5 ± 3.5 nm and −30.4 ± 2.3 mV, respectively, and a quasi-spherical shape relative to pristine SPIONs. Fourier transform infrared (FTIR) analysis and estimation of free carboxylic groups supported the preparation of the CLA-coated PTX-SPIONs@HRH. CLA-coated PTX-SPIONs@HRH exhibited high PTX loading efficiency (98.5%) and sustained release in vitro, with a marked dose dependent anti-proliferative activity in A549 lung adenocarcinoma cells, complimented by an enhanced cellular uptake. CLA-coated PTX-SPIONs@HRH significantly reduced secretion levels of VEGF-A in human dermal microvascular endothelial cells from 46.9 to 35.6 pg/mL compared to untreated control. A 76.6% tumor regression was recorded in a lung tumor xenograft mouse model following intervention with CLA-coated PTX-SPIONs@HRH, demonstrating tumor targetability and angiogenesis inhibition. CLA-coated PTX-SPIONs@HRH enhanced the half-life of PTX by almost 2-folds and demonstrated a prolonged PTX plasma circulation time from a subcutaneous injection (SC). Thus, it is suggested that CLA-coated PTX-SPIONs@HRH could provide a potential effective treatment modality for non-small-cell lung carcinoma as a nanomedicine.
KW - HRH peptide
KW - SPIONs
KW - angiogenesis
KW - non-small-cell lung carcinoma
KW - paclitaxel
KW - vascular endothelial growth factor targeting
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U2 - 10.1021/acsabm.3c00224
DO - 10.1021/acsabm.3c00224
M3 - Article
C2 - 37384895
AN - SCOPUS:85164911079
SN - 2576-6422
VL - 6
SP - 2747
EP - 2759
JO - ACS Applied Bio Materials
JF - ACS Applied Bio Materials
IS - 7
ER -