Paclitaxel-Trastuzumab Mixed Nanovehicle to Target HER2-Overexpressing Tumors

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.

Trastuzumab: More than a Guide in HER2-Positive Cancer Nanomedicine

“…As consequence and since HER2 is not only overexpressed in this type of cancer, many studies in the preliminary stages have proposed the administration of this adjuvant therapy to treat other types of HER2+ tumors, including ovarian, bladder, and lung ones [91]. In this way, the Tmab-decorated NPs developed to target these solid tumors other than breast tumors can be already found in the literature [48][49][50]62,64].…”

“…For instance, Choi et al chose it to make the comparative study that was aforementioned [ 42 ]. Similarly, Zhou et al [ 47 ], Mehata et al [ 6 ], and Nieto et al [ 48 ] decorated the surface of their synthesized NPs with Tmab by taking advantage of this method to treat HER2+ breast carcinoma cells. The first authors [ 47 ] developed PLGA-poly- l -histidine (Phis)-polyethylene glycol (PEG) NPs and loaded them with doxorubicin.…”

“…Mehata et al [ 6 ] obtained TPGS-g-chitosan NPs that carried docetaxel to the mentioned cells and, finally, Nieto el al. [ 48 ] synthesized alginate-piperazine NPs to improve and guide paclitaxel treatment. In addition, these last authors also proved that their nanosystem was able to reduce the rate of survival of other types of cancer cells that also overexpress HER2, such as ovarian tumor cells.…”

Microbial Exopolysaccharides as Drug Carriers

“…Sometimes however, the drug is attached to the surface of the carrier by means of electrostatic interactions or covalent bound. In this case, surface engineering experiments must be performed previously to modify the functional groups of the polymer and to allow a successful drug attachment [ 41 , 42 ].…”

“…These beads are suitable for encapsulating different pulmonary and oral delivery compounds [ 54 ], and can even be included in scaffolds to enhance their properties for potential tissue engineering applications [ 55 ]. Moreover, alginate’s available functional groups permit its surface to be functionalized, allowing drug attachment [ 41 ].…”