title: Poly(styrene-co-maleic acid)-based pH-sensitive liposomes mediate cytosolic delivery of drugs for enhanced cancer chemotherapy.
abstract: pH-responsive polymers render liposomes pH-sensitive and facilitate the intracellular release of encapsulated payload by fusing with endovascular membranes under mildly acidic conditions found inside cellular endosomes. The present study reports the use of high-molecular weight poly(styrene-co-maleic acid) (SMA), which exhibits conformational transition from a charged extended structure to an uncharged globule below its pK(1) value, to confer pH-sensitive property to liposomes. The changes in the co-polymer chain conformation resulted in destabilization of the liposomes at mildly acidic pH due to vesicle fusion and/or channel formation within the membrane bilayer, and ultimately led to the release of the encapsulated cargo. The vesicles preserved their pH-sensitivity and stability in serum unlike other polymer-based liposomes and exhibited no hemolytic activity at physiological pH. The lysis of RBCs at endosomal pH due to SMA-based liposome-induced alterations in the bilayer organization leading to spherocyte formation indicated the potential of these vesicles to mediate cytosolic delivery of bio-active molecules through endosome destabilization. The SMA-loaded liposomes exhibiting excellent cytocompatibility, efficiently delivered chemotherapeutic agent 5-Fluorouracil (5-FU) within colon cancer cells HT-29 in comparison to neat liposomes. This caused increased cellular-availability of the drug, which resulted in enhanced apoptosis and highlighted the clinical potential of SMA-based vesicles.
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, India.
authors.forename: Shubhadeep
authors.initials: S
authors.lastname: Banerjee
authors.forename: Kacoli
authors.initials: K
authors.lastname: Sen
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Pal
authors.forename: Sujoy K
authors.initials: SK
authors.lastname: Guha
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry; D019073:HT29 Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008297:Male; D008298:Maleates / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D041681:NIH 3T3 Cells; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000737:chemistry; D011137:Polystyrenes / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D008298:Maleates; D010713:Phosphatidylcholines; D011137:Polystyrenes; C024074:styrene-maleic acid polymer; C010942:1,2-distearoyllecithin; D005472:Fluorouracil