PSMA Antibody-Conjugated Pentablock Copolymer Nanomicellar Formulation for Targeted Delivery to Prostate Cancer

Abstract

The main purpose of this study was to develop a prostate-specific membrane antigen (PSMA) antibody-conjugated drug-loaded nanomicelles using MPEG--PLA-PCL-PLA-PEG-NH2 pentablock copolymer for targeted delivery of hydrophobic anticancer drugs to prostate cancer cells. During this experiment, monomers of L-lactide, ε-caprolactone, poly(ethylene glycol)-methyl ether, and poly(ethylene glycol)-NH2 were used to prepare pentablock copolymer using the ring opening technique. The pentablock nanomicellar (PBNM) formulation was prepared by the evaporation-rehydration method. The resultant pentablock nanomicelles were then conjugated with PSMA antibody resulting in PSMA-Ab-PTX-PBNM. Both the block copolymers and the nanomicelles were analyzed by hydrogen nuclear magnetic resonance (H-NMR), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The obtained nanomicelles (NM) were then analyzed for size and zeta potential using dynamic light scattering-dynamic laser scattering (DLS) and then further submitted to H-NMR and TEM analyses. The XRD, FTIR, and the H-NMR analyses confirmed the structure of the pentablock copolymers. The average size for conjugated nanomicellar was 45 nm ± 2.5 nm. The average (ζ-potential) was around - 28 mV. H-NMR and FTIR analysis done on PSMA-coupled paclitaxel-loaded PBNM showed peaks characteristic of the drug (paclitaxel) and the polymer, confirming the successful encapsulation. TEM analysis showed well-defined spherical morphology and confirmed the size range obtained by the DLS. In vitro release studies revealed sustained slow of PTX in phosphate buffer solution (PBS). Confocal scanning microscopy (TEM) of coumarin6-loaded in PBNM indicated that pentablock nanomicelles were internalized into the prostate cancer (PC-3) cells. Cell proliferation assay showed that nanomicelles ferried paclitaxel into the PC-3 cells and subsequently reduced the cell proliferation. The results depict PTX-PBNM-Ab as a suitable carrier for targeted delivery of drugs to prostate cancer cells.

Functionalized Particles Designed for Targeted Delivery

“…Only in the last two years, many kinds of aliphatic homo and copolymers have been used for fabrication of nano and microcarriers of bioactive substances. The microcarriers were prepared in the form of nanoparticles [ 89 , 90 , 91 , 92 , 93 , 94 ], polymeric micelles [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ], and nanocapsules [ 105 ].…”

“…Only in the last two years, many kinds of aliphatic hom and copolymers have been used for fabrication of nano and microcarriers of bioactiv substances. The microcarriers were prepared in the form of nanoparticles [89][90][91][92][93][94], poly meric micelles [95][96][97][98][99][100][101][102][103][104], and nanocapsules [105]. It is worth noting that poly(β-butyrolactones) and polylactides contain chiral carbon atoms in the main chains.…”