Antibody Conjugated PLGA Nanocarriers and Superparmagnetic Nanoparticles for Targeted Delivery of Oxaliplatin to Cells from Colorectal Carcinoma

Abstract

Anti-CD133 monoclonal antibody (Ab)-conjugated poly(lactide-co-glycolide) (PLGA) nanocarriers, for the targeted delivery of oxaliplatin (OXA) and superparamagnetic nanoparticles (IO-OA) to colorectal cancer cells (CaCo-2), were designed, synthesized, characterized, and evaluated in this study. The co-encapsulation of OXA and IO-OA was achieved in two types of polymeric carriers, namely, PLGA and poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) by double emulsion. PLGA_IO-OA_OXA and PEGylated PLGA_IO-OA_OXA nanoparticles displayed a comparable mean diameter of 207 ± 70 nm and 185 ± 119 nm, respectively. The concentration of the released OXA from the PEGylated PLGA_IO-OA_OXA increased very rapidly, reaching ~100% release after only 2 h, while the PLGA_IO-OA_OXA displayed a slower and sustained drug release. Therefore, for a controlled OXA release, non-PEGylated PLGA nanoparticles were more convenient. Interestingly, preservation of the superparamagnetic behavior of the IO-OA, without magnetic hysteresis all along the dissolution process, was observed. The non-PEGylated nanoparticles (PLGA_OXA, PLGA_IO-OA_OXA) were selected for the anti-CD133 Ab conjugation. The affinity of Ab-coated nanoparticles for CD133-positive cells was examined using fluorescence microscopy in CaCo-2 cells, which was followed by a viability assay.

Multifunctional nanoparticle for cancer therapy

“… 20 , 21 Additionally, PLGA nanoparticles possess free carboxyl end‐groups and can be modified as multifunctional nanoparticles, by connecting other bioactivation agents through covalent bonds. 22 Based on the delivered ability of PLGA, there are three main modification strategies for cancer therapy, namely encapsulation, coating, and covalent modification. Initially, these water‐soluble agents can be encapsulated in the PLGA core, while the hydrophobic agents are loaded in the PLGA shell, forming a core–shell structure.…”

“…As PLGA nanoparticles possess both hydrophilicity and hydrophobicity, they have the potential to form a water/oil/water (W/O/W) core–shell structure by the compatibility principle 20,21 . Additionally, PLGA nanoparticles possess free carboxyl end‐groups and can be modified as multifunctional nanoparticles, by connecting other bioactivation agents through covalent bonds 22 . Based on the delivered ability of PLGA, there are three main modification strategies for cancer therapy, namely encapsulation, coating, and covalent modification.…”

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells

“…On the other hand, nanocarrier-based drug delivery systems have been spotlighted in last several decades due to their superiority in drug targeting issues [ 17 , 18 , 19 , 20 , 21 ]. Due to their small size, nanocarriers are believed to be an ideal candidate for tumor targeting [ 17 , 18 ].…”

“…On the other hand, nanocarrier-based drug delivery systems have been spotlighted in last several decades due to their superiority in drug targeting issues [ 17 , 18 , 19 , 20 , 21 ]. Due to their small size, nanocarriers are believed to be an ideal candidate for tumor targeting [ 17 , 18 ]. Since the surface of nanocarriers such as polymeric nanoparticles can be easily decorated with targeting moieties such as monoclonal antibodies, they can then be specifically delivered to the tumor with a minimization of side effects against normal cells [ 17 , 18 ].…”

“…Due to their small size, nanocarriers are believed to be an ideal candidate for tumor targeting [ 17 , 18 ]. Since the surface of nanocarriers such as polymeric nanoparticles can be easily decorated with targeting moieties such as monoclonal antibodies, they can then be specifically delivered to the tumor with a minimization of side effects against normal cells [ 17 , 18 ]. Furthermore, nanocarriers based on polymeric nanoparticles or micelles can be designed to stimulate of tumor tissues and then deliver the anticancer drug to the tumor tissues specifically [ 18 , 19 , 20 , 21 ].…”