Abstract Title

EVALUATION OF A "TROJAN HORSE" STRATEGY TO COMBAT NEUROBLASTOMA

Presenter Name

Gaile Vitug

Abstract

Neuroblastoma (NB) is the most common type of cancer in children less than a year old and stems from early neural cells that fail to differentiate into neurons or adrenal medulla cells. Upon initial diagnosis, 67% of cases show metastases to the lymph nodes or other organs; therefore, chemotherapy effectiveness is of particular concern. Currently, there are no FDA approved treatments or designs specifically available for NB patients and most are designed for different types of adult cancers with dose-limiting toxicities as a significant concern. Present study evaluates the therapeutic potential of a novel drug delivery system utilizing reconstituted high density lipoprotein (rHDL) containing hydrophobic analogue of Cisplatin (CisX) nanoparticles that act as a “Trojan horse” towards tumor cells. The characterization studies of CisX reveal sizes of the particles ranging from 14 nm to 164.9 nm with a mean diameter of 69.46 nm. Encapsulation efficiency was observed to be 26.34%. The cytotoxicity studies of free CisX vs rHDL-CisX towards NB cell line SJ-N-KP show 5.1 times lower IC50 value for the rHDL-CisX. This study reveals the potential of rHDL as a novel delivery method for chemotherapeutic drugs in the treatment of NB and warrants more investigation.

Presentation Type

Poster

Purpose (a):

Neuroblastoma (NB) is the most common type of cancer in children less than a year old and stems from early neural cells that fail to differentiate into neurons or adrenal medulla cells. Upon initial diagnosis, 67% of cases show metastases to the lymph nodes or other organs; therefore, chemotherapy effectiveness is of particular concern. Currently, there are no FDA approved treatments or designs specifically available for NB patients and most are designed for different types of adult cancers with dose-limiting toxicities as a significant concern. Present study evaluates the therapeutic potential of a novel drug delivery system utilizing reconstituted high density lipoprotein (rHDL) containing hydrophobic analogue of Cisplatin (CisX) nanoparticles that act as a “Trojan horse” towards tumor cells.

Methods (b):

  • rHDL-CisX nanoparticles was prepared by lyophilization followed by cholate dialysis
  • Chemical composition of rHDL-CisX nanoparticles was determined using BCA protein assay kit and enzymatic reagent assay kits (phospolipid C and cholesterol E)
  • Encapsulation efficiency of CisX was determined by Inductively Coupled Plasma Mass Spectrometry (ICPMS)
  • Size estimations were determined using dynamic light scattering
  • The Neuroblastoma cell line, SJ-N-KP, was plated in 96 well plates and incubated at 5% CO2 at 37ºC for 72 hours
  • Comparative cytotoxicity was examined by CCK-8 assay (Dojindo) using Free CisX and rHDL-CisX nanoparticles at various concentrations

Results (c):

The characterization studies of CisX reveal sizes of the particles ranging from 14 nm to 164.9 nm with a mean diameter of 69.46 nm. An encapsulation efficiency was observed to be 26.34%. The cytotoxicity studies of free CisX vs rHDL-CisX towards NB cell line SJ-N-KP show 5.1 times lower IC50 value for the rHDL-CisX.

Conclusions (d):

This study reveals the potential of rHDL as a novel delivery method for chemotherapeutic drugs in the treatment of NB and warrants more investigation. Additional studies using rHDL towards normal cells are also needed to further evaluate their therapeutic potential.

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EVALUATION OF A "TROJAN HORSE" STRATEGY TO COMBAT NEUROBLASTOMA

Neuroblastoma (NB) is the most common type of cancer in children less than a year old and stems from early neural cells that fail to differentiate into neurons or adrenal medulla cells. Upon initial diagnosis, 67% of cases show metastases to the lymph nodes or other organs; therefore, chemotherapy effectiveness is of particular concern. Currently, there are no FDA approved treatments or designs specifically available for NB patients and most are designed for different types of adult cancers with dose-limiting toxicities as a significant concern. Present study evaluates the therapeutic potential of a novel drug delivery system utilizing reconstituted high density lipoprotein (rHDL) containing hydrophobic analogue of Cisplatin (CisX) nanoparticles that act as a “Trojan horse” towards tumor cells. The characterization studies of CisX reveal sizes of the particles ranging from 14 nm to 164.9 nm with a mean diameter of 69.46 nm. Encapsulation efficiency was observed to be 26.34%. The cytotoxicity studies of free CisX vs rHDL-CisX towards NB cell line SJ-N-KP show 5.1 times lower IC50 value for the rHDL-CisX. This study reveals the potential of rHDL as a novel delivery method for chemotherapeutic drugs in the treatment of NB and warrants more investigation.