Abstract
Paclitaxel is one of the most widely used chemotherapeutic agents thanks to its effectiveness and broad spectrum of antitumor activity. However, it has a very poor aqueous solubility and a limited specificity. To solve these handicaps, a novel paclitaxel-trastuzumab targeted transport nanosystem has been developed and characterized in this work to specifically treat cancer cells that overexpress the human epidermal growth factor receptor-2 (HER2). Methods: Alginate and piperazine nanoparticles were synthetized and conjugated with paclitaxel:β-cyclodextrins complexes and trastuzumab. Conjugated nanoparticles (300 nm) were characterized and their internalization in HER2-overexpressing tumor cells was analyzed by immunofluorescence. Its specific antitumor activity was studied in vitro using human cell lines with different levels of HER2-expression. Results: In comparison with free paclitaxel:β-cyclodextrins complexes, the developed conjugated nanovehicle presented specificity for the treatment of HER2-overpressing cells, in which it was internalized by endocytosis. Conclusions: It seems that potentially avoiding the conventional adverse effects of paclitaxel treatment could be possible with the use of the proposed mixed nanovehicle, which improves its bioavailability and targets HER2-positive cancer cells.
Highlights
Cancer therapy improvement has become one of the most important health challenges for the time being due to the high incidence of this disease
Stable APPZ Synthesis and Characterization. As it was mentioned before, APPZ were synthesized by dropping a piperazine aqueous solution over a sodium alginate one, in different molar ratios, at pH 4.7
The best size/surface charge relationship was achieved with a 0.25 piperazine:alginate molar ratio and APPZ developed in this manner were selected for further characterization
Summary
Cancer therapy improvement has become one of the most important health challenges for the time being due to the high incidence of this disease. As most employed cytotoxic agents affect cell cycle progression, cancer cells are killed by antitumor drugs, and normal cells that proliferate rapidly [3,4] Such side effects are present, for instance, in paclitaxel (PTX)-containing treatments. Due to its broad spectrum of antitumor activity and high effectiveness, it is normally employed to treat breast, ovarian, and non-small cell lung cancers [6] In this manner, PTX is one of the three most administered chemotherapy agents today, but it presents an important handicap. Its aqueous solubility is very limited (0.3–0.5 μg/mL) and intravenous PTX’s formulations have had to be developed [7] Among them, they are only two that are approved to be used in clinic and the major drawback is that, in the most used one [5], PTX is dissolved into a chemical solvent mixture that entails important side effects. Such mixture reduces the taxane effectiveness and limits the doses that can be administered to patients [6]
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