title: Combinatorial-Designed Epidermal Growth Factor Receptor-Targeted Chitosan Nanoparticles for Encapsulation and Delivery of Lipid-Modified Platinum Derivatives in Wild-Type and Resistant Non-Small-Cell Lung Cancer Cells.
abstract: Development of efficient and versatile drug delivery platforms to overcome the physical and biological challenges in cancer therapeutics is an area of great interest, and novel materials are actively sought for such applications. Recent strides in polymer science have led to a combinatorial approach for generating a library of materials with different functional identities that can be "mixed and matched" to attain desired characteristics of a delivery vector. We have applied the combinatorial design to chitosan (CS), where the polymer backbone has been modified with polyethylene glycol, epidermal growth factor receptor-binding peptide, and lipid derivatives of varying chain length to encapsulate hydrophobic drugs. Cisplatin, cis-([PtCl2(NH3)2]), is one of the most potent chemotherapy drugs broadly administered for cancer treatment. Cisplatin is a hydrophilic drug, and in order for it to be encapsulated in the developed nanosystems, it was modified with lipids of varying chain length. The library of four CS derivatives and six platinum derivatives was self-assembled in aqueous medium and evaluated for physicochemical characteristics and cytotoxic effects in platinum-sensitive and -resistant lung cancer cells. The results show that the lipid-modified platinate encapsulation into CS nanoparticles significantly improved cellular cytotoxicity of the drug. In this work, we have also reinforced the idea that CS is a multifaceted system that can be as successful in delivering small molecules as it has been as a nucleic acids carrier.
authors.affiliation: CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde , R. Central da Gandra 1317, 4585-116 Gandra, Portugal.|Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto , R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.|Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115-5000, United States.
authors.forename: Ana Vanessa
authors.initials: AV
authors.lastname: Nascimento
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115-5000, United States.
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.affiliation: CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde , R. Central da Gandra 1317, 4585-116 Gandra, Portugal.|Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto , Rua do Campo Alegre 823, 4050-313 Porto, Portugal.
authors.forename: Hassan
authors.initials: H
authors.lastname: Bousbaa
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmacy, University of Porto , R. Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal.
authors.forename: Domingos
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde , R. Central da Gandra 1317, 4585-116 Gandra, Portugal.|I3S, Instituto de Investigação e Inovação em Saúde and INEB - Instituto de Engenharia Biomédica, Universidade do Porto , Rua do Campo Alegre 823, 4150 Porto, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts 02115-5000, United States.
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry*; D002945:Cisplatin / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D054852:Small Molecule Libraries / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D008055:Lipids; D009944:Organoplatinum Compounds; D054852:Small Molecule Libraries; D011092:Polyethylene Glycols; D048271:Chitosan; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin
keywords: chitosan; combinatorial-designed nanoparticles; epidermal growth factor receptor; lipid modification; non-small-cell lung cancer; platinates