Folate-conjugated thermosensitive O-maleoyl modified chitosan micellar nanoparticles for targeted delivery of erlotinib

[Display omitted] •Organo-soluble chitosan complex was chemically modified with maleic anhydride.•Amphiphilic chitosan-derivative was produced by NIPAAm and OA polymerization.•Folate-armed self-assembled nanoparticles displayed thermo-responsive release of erlotinib.•Hemocompatibility, biocompatibility and cancer cell targeting effects were demonstrated.•Nanoparticles as smart injectable material could be used for effective cancer therapy. In the present work, new self-assembled nanoparticles (NPs) were engineered using biocompatible and biodegradable natural polymer, chitosan (CS). The complexation of CS with sodium dodecyl sulfate (SDS) facilitated the regioselective chemical modification of CS hydroxyl groups with maleic anhydride, and produced polymerizable precursor of CS that was further grafted with N-isopropylacrylamide (NIPAAm) as temperature-sensitive moiety and oleic acid (OA) as hydrophobic monomer. After removal of SDS complex, the free amino groups were functionalized with folic acid (FA) to form folate-(PNIPAAm-co-OA)-g-CS micellar NPs. The NPs were loaded with a tyrosine kinase inhibitor erlotinib (ETB), which was carried out above the lower critical solution temperature (LCST) of micelles solution. The structure, size distribution, zeta potential, thermal stability, elemental composition, morphology and LCST of the synthesized micelles were characterized. The cellular uptake and cell cytotoxicity analyses revealed that the developed smart folate-(PNIPAAm-co-OA)-g-CS micellar NPs could be used for effective cancer therapy as an injectable tumor targeting nanocarrier.