Bladder cancer

Bladder cancer (BC) is a heterogeneous disease which presents several molecular characteristics associated with different clinical outcomes. Urothelial or transitional cell carcinoma (TCC); represent the most frequent type of bladder cancer and are classified into two subtypes tumors depending on the formation pathway: non-muscle invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC).
NMIBC are confined to the mucosa (stage Ta, CIS) or submucosa (stage T1); are accounted for 60–80% of the diagnosed bladder cancer cases. The histological evaluation is the gold standard for the classification of the tumor allowing the implementation of the best possible therapeutic alternative. This strategy also allows the evaluation of the risks of recurrence and progression of the disease. However, recent studies have focused on tumor classifications considering their molecular characteristics in order to diagnose tumor subtypes and establish the best possible therapeutic alternative.

Transitional cell carcinomas

Molecular analyses have shown that approximately 75% of transitional cell carcinomas overexpress epidermal growth factor receptors (EGFR); their level of expression is directly related to advanced stage tumors. EGFR receptors consist of a family of four receptors, EGFR (ErbB1/Her1), EGFR2 (ErbB2/Her2), EGFR3 (ErbB3/Her3), and EGFR4 (ErbB4/Her4); which play an important role in the control of cell proliferation and differentiation. However, the EGFR signaling pathway has also with tumor progression and development; through the activation of pathways that result in angiogenesis and increased metastatic potential.

Therefore nanotechnology tools have been widely used as drug delivery systems in cancer therapy research. These tools have proven to be effective for cancer therapy through controlled drug delivery at specific sites; providing a higher intratumoral concentration of chemotherapeutics. It has also shown by our group that nanotechnology-based drug delivery systems could be an important alternative to overcome the resistance developed by cancer cells to drugs.

The pharmacological action

Lapatinib (LAP) is an intracellular inhibitor of tyrosine kinase. Therefore, for its pharmacological action, it is crucial that lapatinib is by tumor cells. LAP carried in nanocapsules ensures this increase cellular uptake through the capacity of internalization of the nanocapsules by endocytosis process of the cells. In addition, lapatinib-loaded nanocapsules enable an improvement in its oral bioavailability; aqueous solubility and could minimize the ability of LAP to bind albumin or alpha-1 glycoprotein in the blood.
Herein, we synthesized lapatinib-loaded nanocapsules (NC-LAP); in order to evaluate its cytotoxic activity against HER-positive bladder cancer cells. In conclusion, we demonstrate that Lapatinib-loaded nanocapsules showed cytotoxic effect against HER-positive bladder cancer cell. NC-LAP reduced the viability of T24 bladder cells, inducing G0/G1 cell cycle arrest through up-regulation of p21; reducing colony formation and leading cells to apoptosis with an increase of Bax/Bcl-2 expression. However, further studies are necessary to understand the pharmacokinetic and toxicological effects of NC-LAP formulation.