title: Ligand-decorated click polypeptide derived nanoparticles for targeted drug delivery applications.
abstract: A ligand decorated, synthetic polypeptide block copolymer platform with environment-responsive capabilities was designed. We evaluated the potential of this system to function as a polymersome for targeted-delivery of a systemic chemotherapy to tumors. Our system employed click chemistry to provide a pH-responsive polypeptide block that drives nanoparticle assembly, and a ligand (folic acid) conjugated PEG block that targets folate-receptor over-expressing cancer cells. These nanocarriers were found to encapsulate a high loading of conventional chemotherapeutics (e.g. doxorubicin at physiological pH) and release the active therapeutic at lysosomal pH upon cellular uptake. The presence of folic acid on the nanoparticle surface facilitated their active accumulation in folate-receptor-overexpressing cancer cells (KB), compared to untargeted carriers. Folate-targeted nanoparticles loaded with doxorubicin also showed enhanced tumor accumulation in folate-receptor positive KB xenografts, resulting in the suppression of tumor growth in an in vivo hind flank xenograft mouse model.
authors.affiliation: Department of Chemical Engineering and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Mohiuddin A
authors.initials: MA
authors.lastname: Quadir
authors.affiliation: Department of Chemical Engineering and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Morton
authors.affiliation: Department of Chemical Engineering and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Mensah
authors.affiliation: Department of Chemical Engineering and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Shopsowitz
authors.affiliation: Department of Chemical Engineering and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Dobbelaar
authors.affiliation: Department of Chemical Engineering and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Nicole
authors.initials: N
authors.lastname: Effenberger
authors.affiliation: Department of Chemical Engineering and Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, United States. Electronic address: hammond@mit.edu.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Hammond
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005492:Folic Acid; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D010455:Peptides; D011108:Polymers
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D010455:Peptides; D011108:Polymers; D004317:Doxorubicin; D005492:Folic Acid
keywords: Block copolymers; Drug delivery; Nanocarriers; Poly (propargyl L-glutamate)