Intracellular Targeted Nanocapsules Containing Nanobiotherapeutic Suppress Lung, Liver, Breast and Cervix Cancer Cell Lines by Prodrug Activation or Removal of Intracellular Tyrosine

Background: Unlike melanoma, cancer cell lines like Hepa 1-6 liver cancer line, A549 lung cancer line, Hela cervical cancer line, and MCF7 breast cancer line do not have over expressed tyrosinase to convert quercetin into its active o-quinone. Furthermore, they do not need extracellular supply of tyrosine for growth, since they can produce this intracellularly. Method: In this study we used (1) nanocapsules containing polyhemoglobin-tyrosinase (PolyHb-Tyr-nano) to activate the prodrug quercetin. (2) We also located these nanocapsules intracellularly to remove the tyrosine produced intracellularly. We studied this in 4 cancer cell lines: Hepa 1-6 liver cancer line, A549 lung cancer Hela cervical cancer line, and MCF7 breast cancer line. Results: (1) Nanocapsules containing polyhemoglobin-tyrosinase (PolyHb-Tyr-nano) activate the prodrug resulting in increased intracellular o-quinone and suppression of the cancer cell lines. (2) Intracellular located nanocapsules containing polyhemoglobin-tyrosinase (PolyHb-Tyr-nano) were able to lower intracellular tyrosine and suppressed the growth of these cancer cell lines. Furthermore, for PolyHb-Tyr-nano, the dosage needed to suppress 50% of the liver cancer cells (LD50), is 0.7808 mg/ml. In the normal liver cells, the LD50 is 84181 mg/ml. Compared to the result of quercetin activation of LD50 (2.73mg/ml in liver cancer, and 74.18mg/ml in normal hepatocytes). Conclusion: Promising result of using nanocapsules containing polyhemoglobin-tyrosinase (PolyHb-Tyr-nano) to (1) activate the prodrug quercetin and (2) locating these nanocapsules intracellularly to remove the tyrosine produced intracellularly. Method (2) appears to be effective with virtually no adverse effects compared to activation of quercetin.