Selective N-Alkylation of beta-Alanine Facilitates the Synthesis of a Poly(amino acid)-Based Theranostic Nanoagent

    Authors

    S. Santra;J. M. Perez

    Comments

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    Abbreviated Journal Title

    Biomacromolecules

    Keywords

    ALPHA-AMINO ESTERS; CLICK CHEMISTRY; CANCER-THERAPY; DRUG-DELIVERY; PLGA; NANOPARTICLES; BLOCK-COPOLYMER; ACID ESTERS; PACLITAXEL; POLYMERIZATION; CELLS; Biochemistry & Molecular Biology; Chemistry, Organic; Polymer Science

    Abstract

    The development of functional amino acid-based polymeric materials is emerging as a platform to create biodegradable and nontoxic nanomaterials for medical and biotechnology applications. In particular, facile synthetic routes for these polymers and their corresponding polymeric nanomaterials would have a positive impact in the development of novel biomaterials and nanoparticles. However, progress has been hampered by the need to use complex protection-deprotection methods and toxic phase transfer catalysts. In this study, we report a facile, single-step approach for the synthesis of an N-alkylated amino acid as an AB-type functional monomer to generate a novel pseudo-poly(amino acid), without using the laborious multistep, protection-deprotection methods. This synthetic strategy is reproducible, easy to scale up, and does not produce toxic byproducts. In addition, the synthesized amino acid-based polymer is different from conventional linear polymers as the butyl pendants enhance its solubility in common organic solvents and facilitate the creation of hydrophobic nanocavities for the effective encapsulation of hydrophobic cargos upon nanoparticle formation. Within the nanoparticles, we have encapsulated a hydrophobic DiI dye, and a therapeutic drug, Taxol. In addition, we have conjugated folic acid as a folate receptor-targeting ligand for the targeted delivery of the nanoparticles to cancer cells expressing the folate receptor. Cell cytotoxicity studies confirm the low toxicity of the polymeric nanoparticles, and drug-release experiments with the Taxol-encapsulated nanoparticles only exhibit cytotoxicity upon internalization into cancer cells expressing the folate receptor. Taken together, these results suggested that our synthetic strategy can be useful for the one-step synthesis of amino acid-based small molecules, biopolymers, and theranostic polymeric nanoagents for the targeted detection and treatment of cancer.

    Journal Title

    Biomacromolecules

    Volume

    12

    Issue/Number

    11

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    3917

    Last Page

    3927

    WOS Identifier

    WOS:000296830600010

    ISSN

    1525-7797

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