Nano-based strategies to overcome p-glycoprotein-mediated drug resistance.
BACKGROUND
The discussion about cancer treatment has a long history. Chemotherapy, one of the promising approaches in cancer therapy, is limited in the clinic as plenty of factors evolve and prevent appropriate therapeutic response to drugs. Multi-drug resistance (MDR), which is mostly P-glycoprotein-mediated, is described as the most well-known impediment in this contribution. It extrudes several agents out of cells, arising MDR and decreasing the bioavailability of drugs. Hence, cancer cells become insensitive to chemotherapy.


METHODS
Many agents have been developed to reverse MDR, but it is difficult to deliver them into cancer sites and cancer cells. The emerging nano-based drug delivery systems have been more effective to overcome P-glycoprotein-mediated MDR by increasing the intracellular delivery of these agents. Here, we represent systems including siRNA-targeted inhibition of P-gp, monoclonal antibodies, natural extracts, conventional inhibitors, hard nanoparticles and soft nanoparticles as delivery systems in addition to a novel approach applying cell penetrating peptides.


CONCLUSIONS
Overcoming cancer drug resistance using innovative nanotechnology is being increasingly used and developed. Among resistance mechanisms, drug efflux transporter inhibitors and MDR gene expression silencing are among the those being investigated. In the near future, it seems some of these nanomedical approaches might become the mainstay of effective treatment of important human conditions like cancer.
a Student Research Committee, Faculty of Advanced Medical Sciences and Research Center for Pharmaceutical Nanotechnology , Tabriz University of Medical Sciences , Tabriz , Iran.
Mehri
M
Niazi
b Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy , Tabriz University of Medical Sciences , Tabriz , Iran.
Parvin
P
Zakeri-Milani
a Student Research Committee, Faculty of Advanced Medical Sciences and Research Center for Pharmaceutical Nanotechnology , Tabriz University of Medical Sciences , Tabriz , Iran.
Saeedeh
S
Najafi Hajivar
a Student Research Committee, Faculty of Advanced Medical Sciences and Research Center for Pharmaceutical Nanotechnology , Tabriz University of Medical Sciences , Tabriz , Iran.
Mehdi
M
Soleymani Goloujeh
a Student Research Committee, Faculty of Advanced Medical Sciences and Research Center for Pharmaceutical Nanotechnology , Tabriz University of Medical Sciences , Tabriz , Iran.
Nasrin
N
Ghobakhlou
c Drug Applied Research Center and Faculty of Pharmacy , Tabriz University of Medical Sciences , Tabriz , Iran.
Javid
J
Shahbazi Mojarrad
c Drug Applied Research Center and Faculty of Pharmacy , Tabriz University of Medical Sciences , Tabriz , Iran.
Hadi
H
Valizadeh
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D020868:Gene Silencing; D006801:Humans; D053758:Nanoparticles; D036103:Nanotechnology / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents
Cancer; P-glycoprotein; chemotherapy; multi drug resistance; nanomedical approaches