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Small cell lung cancer (SCLC) is one of the most malignant cancers in the world and 5-year survival rate has not been significantly improved with conventional chemotherapy. Targeting treatment may be a promising alternative to enhance the antitumor efficacy. Present study was aimed at establishing a targeting nanodrug delivery system for SCLC therapy. A targeting peptide (AHSGMYP, named AP), screened in H446 cells by phage display technology, was conjugated to the docetaxel (DTX) encapsulated polylactic acid nanoparticles (DN) to prepare the targeting DTX nanoparticles (AP-DN). Cell cytotoxicity, cellular uptake, therapeutic efficacy and biodistribution of AP-DN were investigated in vitro and in vivo experiment. The mean particle size of AP-DN was 260 nm with encapsulation efficiency >94% and a sustained release profile. Cytotoxicity of AP-DN against H446 cell was superior to that of DTX and DN. AP-DN exhibited excellent antitumor efficacy and particularly effectively inhibited the liver metastases with better tolerance. Results of cellular uptake and biodistribution indicated that the excellent antitumor efficacy of AP-DN was attributed to both the increased accumulation of drug and cellular uptake. To our knowledge, this is the first report on establishing SCLC targeting delivery system which offers a potential therapeutic alterative for SCLC therapy.

Original publication

DOI

10.1016/j.ijpharm.2015.08.042

Type

Journal article

Journal

International Journal of Pharmaceutics

Publication Date

15/10/2015

Volume

494

Pages

337 - 345