Q2. What are the contributions mentioned in the paper "Advanced targeted therapies in cancer: drug nanocarriers, the future of chemotherapy" ?
Although targeted therapies can be achieved directly by altering specific cell signaling by means of monoclonal antibodies or small molecules inhibitors, this review focuses on indirect targeted approaches that mainly deliver chemotherapeutic agents to molecular targets overexpressed on the surface of tumor cells. Despite the many advantages of all the anticancer drug carriers analyzed, only a few of them have reached the FDA approval, in particular, two polymer-protein conjugates, five liposomal formulations and one polymeric nanoparticle are available in the market, in contrast to the sixteen FDA approval of monoclonal antibodies. Moreover, the authors analyze in detail the more promising and advanced preclinical studies of the particular case of polymeric nanoparticles as carriers of different cytotoxic agents to active and passive tumor targeting published in the last 5 years, since they have a huge potential in cancer therapy, being one of the most widely studied nano-platforms in this field in the last years. The interest that these formulations have recently achieved is stressed by the fact that 90 % of the papers based on cancer therapeutics with polymeric nanoparticles have been published in the last 6 years ( PubMed search ). In particular, the authors offer a detailed description of different cytotoxic drug carriers, like liposomes, carbon nanotubes, dendrimers, polymeric micelles, polymeric conjugates and polymeric nanoparticles, in passive and active targeted cancer therapy, by enhancing the permeability and retention or by the functionalization of the surface of the carriers, respectively, emphasizing those that have received FDA approval or are part of the most important clinical studies up to date.
Q3. What are the other drugs that can be used to incorporate?
In addition to small molecular weight anticancer drugs, polymeric nanoparticles are able to incorporate, macromolecules as genes or proteins.
Q4. What is the role of integrin alfaVbeta3 in tumors?
One important aim of peptidic targeting is the integrin alfaVbeta3 that is overexpressed on tumor cells and is involved in angiogenesis.
Q5. What are the advantages of polymeric nanoparticles in cancer therapy?
Polymeric nanoparticles have interesting advantages with respect to other non-viral carriers for siRNA delivery: they are easy to scale-up, have improved stability and better safety regarding both to the materials used and to the manufacturing processes [552].
Q6. What is the role of Pluronic 85 in the drug resistance?
The incorporation of Pluronic 85 enhances the drug solubility, stabilizes the nanoscale formulation, and helps to overcome the multidrug resistance.
Q7. How did Ebrahimnejad and colleagues develop a PLGA nanop?
In order to solve the low solubility of SN-38, the active metabolite of irinotecan, Ebrahimnejad and colleagues developed SN-38-loaded PLGA nanoparticles with efficient drug loading and gradual release profiles.
Q8. What is the role of liposomes in cancer therapy?
As the authors already mentioned above, liposomes have been used in gene cancer therapy, as delivery vehicles that provide protection from renal clearance and enzymatic digestion of siRNAs in plasma, allowing enhanced penetration through the capillary endothelium, and efficient cellular uptake [282, 284].
Q9. What is the promising oral anticancer nanoparticles?
docetaxel and tamoxifen have been other cytotoxic agents to be formulated for oral administration in association with polymeric nanoparticles.
Q10. What is the important information about polymeric nanoparticles?
As mentioned before, polymeric nanoparticles are promising carriers in cancer therapy because they have enabled the efficient co-delivery of multiple cytotoxic compounds and other therapeutic agents with synergic properties to tumors, allowing a longer bloodstream half-life, showing reduced toxicity and improving pharmacokinetics.
Q11. How did Zhang et al. prepare the nanoparticles?
Zhang et al. [463] prepared safe chitosan-polyaspartic acid nanoparticles by ionic gelification technique to deliver 5-fluorouracil in a sustainable way in mice.
Q12. What is the effect of the nanoparticles on tumors?
In vitro, the nanoparticles showed to be highly specificity for both, tumor and tumor endothelial cells, being cytotoxic only against the tumor endothelial cells.
Q13. what is the doxorubicin-loaded multi-walled carbon nanotubes?
These smart carbon nanotubes are able to generate a sustained release of gemcitabine at the lysosomal pH at the tumor site, generating an enhanced cytotoxic response on MCF-7 human breast cancer cell line, compared to free gemcitabine and non-targeted carbon nanotubes.
Q14. What is the peptide sequence that induces cytoplasmic factors to enter the cell?
In addition, certain peptide sequences, known as nuclear localization signals (NLS) can specifically induce cytoplasmic factors to enter and target the cell nucleus [530].
Q15. What is the main reason for the development of oral anticancer polymeric nanoparticles?
The development of oral anticancer polymeric nano-scale formulations is very interesting due to their easy uptake and stress-less characteristics.
Q16. What is the synergy between paclitaxel and the P-gp?
A synergy between paclitaxel and the P-gp targeted siRNA was observed, since the particles loaded with both elements showed higher cytotoxicity in vitro than nanoparticles loaded with paclitaxel alone.
Q17. What are the polymeric micelles currently used in clinical trials?
In spite of the promising characteristics of the polymeric micelles, there are only eight polymeric micelle-based formulations that include anticancer agents currently in clinical trials [338, 353, 354].