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Vectors for inhaled gene therapy in lung cancer. Application for nano oncology and safety of bio nanotechnology.

Zarogouldis P, Karamanos NK, Porpodis K, Domvri K, Huang H, Hohenforst-Schimdt W, Goldberg EP, Zarogoulidis K - Int J Mol Sci (2012)

Bottom Line: Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis.During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle.These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer.

View Article: PubMed Central - PubMed

Affiliation: Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece; E-Mails: kporpodis@yahoo.gr (K.P.); kellybio4@hotmail.com (K.D.); zarog@med.auth.gr (K.Z.) ; Pulmonary Department-Interventional Unit, "Ruhrland Klinik", University of Essen, Essen 45239, Germany.

ABSTRACT
Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer.

No MeSH data available.


Related in: MedlinePlus

Aerosol gene therapy is administered as either liquid aerosol or dry powder. If the nanocomplex is efficiently deposited in the alveoli region it will diffuse through the alveoli membrane to the systemic circulation. It will then circulate to the lymph nodes and cancer tissue. The toxicity of the vector (if any) will be observed in the alveoli membrane. Figure by Paul Zarogoulidis.
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f1-ijms-13-10828: Aerosol gene therapy is administered as either liquid aerosol or dry powder. If the nanocomplex is efficiently deposited in the alveoli region it will diffuse through the alveoli membrane to the systemic circulation. It will then circulate to the lymph nodes and cancer tissue. The toxicity of the vector (if any) will be observed in the alveoli membrane. Figure by Paul Zarogoulidis.

Mentions: Moreover, humidity (99.5%) is a major factor affecting almost all inhaled particles, as the particles tend to expand while moving from the upper airways to the lower [53]. Underlying lung disease (asthma, cystic fibrosis, bronchiectasis, COPD) can also affect the aerosol deposition [54]. The thick mucus production in cystic fibrosis and COPD patients blocks the proper absorption of the aerosol drug formulation by the airway epithelial [55,56]. Asthma bronchoconstriction can further disregulate the drug formulation absorption [57]. Contrariwise, in bronchiectasis, bronchial blood flow is increased, therefore increasing the distribution of the deposited aerosol [58]. Nevertheless, the aerosol product of inhaled insulin, provided indisputable data that the underlying disease is not a factor to stop or prevent its administration [59]. In the case of underlying disease, proper and intense evaluation of glucose levels have to be performed, since the drug absorption cannot be anticipated. In addition, disease control measures have to be taken, such as administration of inhaled bronchodilators, corticosteroids and N-acetylcysteine, to prevent exacerbations. These drugs have also been administered as preparation for inhaled chemotherapy to prevent possible adverse effects [18,19]. Finally, an aspect of the aerosol therapy regarding lung cancer that needs to be clarified is the interaction of the drug formulation with the tumor mass. Several studies conducted on the human airway model included only patients with tumor mass diameter no more than 3–5 cm. It is believed that a larger mass will have necrotic tissue and there is not going to be an interaction or absorption of the drug formulation from the cancer cells. It is assumed, but not investigated, that small tumor masses (3–5 cm in diameter) will absorb an inhaled formulation, but larger ones will not [50]. However, we should also take into consideration that the drug formulation will be deposited in normal alveoli and circulate through the vascular circulation to the vascular bed of the tumor and the rest of the human organs (Figure 1).


Vectors for inhaled gene therapy in lung cancer. Application for nano oncology and safety of bio nanotechnology.

Zarogouldis P, Karamanos NK, Porpodis K, Domvri K, Huang H, Hohenforst-Schimdt W, Goldberg EP, Zarogoulidis K - Int J Mol Sci (2012)

Aerosol gene therapy is administered as either liquid aerosol or dry powder. If the nanocomplex is efficiently deposited in the alveoli region it will diffuse through the alveoli membrane to the systemic circulation. It will then circulate to the lymph nodes and cancer tissue. The toxicity of the vector (if any) will be observed in the alveoli membrane. Figure by Paul Zarogoulidis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3472716&req=5

f1-ijms-13-10828: Aerosol gene therapy is administered as either liquid aerosol or dry powder. If the nanocomplex is efficiently deposited in the alveoli region it will diffuse through the alveoli membrane to the systemic circulation. It will then circulate to the lymph nodes and cancer tissue. The toxicity of the vector (if any) will be observed in the alveoli membrane. Figure by Paul Zarogoulidis.
Mentions: Moreover, humidity (99.5%) is a major factor affecting almost all inhaled particles, as the particles tend to expand while moving from the upper airways to the lower [53]. Underlying lung disease (asthma, cystic fibrosis, bronchiectasis, COPD) can also affect the aerosol deposition [54]. The thick mucus production in cystic fibrosis and COPD patients blocks the proper absorption of the aerosol drug formulation by the airway epithelial [55,56]. Asthma bronchoconstriction can further disregulate the drug formulation absorption [57]. Contrariwise, in bronchiectasis, bronchial blood flow is increased, therefore increasing the distribution of the deposited aerosol [58]. Nevertheless, the aerosol product of inhaled insulin, provided indisputable data that the underlying disease is not a factor to stop or prevent its administration [59]. In the case of underlying disease, proper and intense evaluation of glucose levels have to be performed, since the drug absorption cannot be anticipated. In addition, disease control measures have to be taken, such as administration of inhaled bronchodilators, corticosteroids and N-acetylcysteine, to prevent exacerbations. These drugs have also been administered as preparation for inhaled chemotherapy to prevent possible adverse effects [18,19]. Finally, an aspect of the aerosol therapy regarding lung cancer that needs to be clarified is the interaction of the drug formulation with the tumor mass. Several studies conducted on the human airway model included only patients with tumor mass diameter no more than 3–5 cm. It is believed that a larger mass will have necrotic tissue and there is not going to be an interaction or absorption of the drug formulation from the cancer cells. It is assumed, but not investigated, that small tumor masses (3–5 cm in diameter) will absorb an inhaled formulation, but larger ones will not [50]. However, we should also take into consideration that the drug formulation will be deposited in normal alveoli and circulate through the vascular circulation to the vascular bed of the tumor and the rest of the human organs (Figure 1).

Bottom Line: Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis.During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle.These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer.

View Article: PubMed Central - PubMed

Affiliation: Pulmonary Department-Oncology Unit, "G. Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Thessaloniki 57010, Greece; E-Mails: kporpodis@yahoo.gr (K.P.); kellybio4@hotmail.com (K.D.); zarog@med.auth.gr (K.Z.) ; Pulmonary Department-Interventional Unit, "Ruhrland Klinik", University of Essen, Essen 45239, Germany.

ABSTRACT
Novel aerosol therapeutic modalities have been investigated for lung cancer. Inhaled gene therapy has presented safety and effectiveness previously in cystic fibrosis. However, safety concerns have been raised regarding the safety of non-viral vectors for inhaled gene therapy in lung cancer, and therefore small steps have been made towards this multifunctional treatment modality. During the last decade, numerous new nanocomplexes have been created and investigated as a safe gene delivery nano-vehicle. These formulations are multifunctional; they can be used as either local therapy or carrier for an effective inhaled gene therapy for lung cancer. Herein, we present current and future perspectives of nanocomplexes for inhaled gene therapy treatment in lung cancer.

No MeSH data available.


Related in: MedlinePlus