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Concomitant Delivery of Paclitaxel and NuBCP-9 peptide for synergistic enhancement of cancer therapy
Authors:Dikshi Gupta  Manoj Kumar  Priyanka Tyagi  Sumeet Kapoor  Amit Tyagi  Tarani Kanta Barman  Surender Kharbanda  Donald Kufe  Harpal Singh
Affiliation:1. Centre for Biomedical Engineering, Indian Institute of Technology, HauzKhas, New Delhi, India;2. Institute of Nuclear Medicine & Allied Sciences, DRDO, Timarpur, Delhi, India;3. Department of Medical Oncology, Dana-Farber Cancer Institute Harvard Medical School, Boston, MA, USA
Abstract:Paclitaxel (PTX) is a microtubule inhibitor administered as an albumin-bound nanoformulation for the treatment of breast cancer. However, the effectiveness of PTX is limited by resistance mechanisms mediated in part by upregulation of the anti-apoptotic BCL-2 and P-glycoprotein (P-gp). Present investigation was designed to study the synergistic potential of NuBCP-9 and PTX loaded polymeric nanoparticles to minimize the dose and improve the efficacy and safety. PTX and NuBCP-9 loaded polylactic acid–polyethylene glycol-polypropylene glycol-polyethylene glycol [PLA-(PEG-PPG-PEG)] nanoparticles were prepared by double emulsion solvent evaporation method. PTX and NuBCP-9 loaded NPs displayed an average size of 90?nm with spherical morphology. PTX and NuBCP-9 dual loaded NPs reducedIC50 by ~40-fold and acted synergistically. Treatment of the syngeneic EAT mice with PTX-NuBCP-9/NPs resulted in improved efficacy than that alone treated mice. Overall, the concomitant delivery PTX and NuBCP-9 loaded NPs showed superior activity than that of PTX and NuBCP-9 alone treated mice.
Keywords:Paclitaxel  polymeric nanoparticles  NuBCP-9  BCL-2  NP  nanoparticle  P-gp  Poly-glycoproteins  PTX  Paclitaxel  nab-paclitaxel  albumin based paclitaxel loaded nanoparticles  NuBCP-9  Nur77 derived BCL-2 converting 9 mer peptide  caspase-3-CF  caspase-3-cleaved fragment  EAT  Ehrlich ascites tumor  IP  intraperitoneal  PDI  polydispersity index  TEM  transmission electron microscopy  SEM  scanning electron microscopy  CLSM  confocal laser scanning microscopy
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