title: Targeting docetaxel-PLA nanoparticles simultaneously inhibit tumor growth and liver metastases of small cell lung cancer.
abstract: 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.
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China.
authors: Zhen
authors: Z
authors: Liang
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China.
authors: Nan
authors: N
authors: Yang
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China.
authors: Yao
authors: Y
authors: Jiang
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China.
authors: Chunying
authors: C
authors: Hou
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China.
authors: Ji
authors: J
authors: Zheng
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China.
authors: Jiaojiao
authors: J
authors: Shi
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China.
authors: Rui
authors: R
authors: Zhang
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China.
authors: Dongmei
authors: D
authors: Li
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China. Electronic address: liuyanyong@126.com.
authors: Yanyong
authors: Y
authors: Liu
authors: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, 100005 Beijing, China. Electronic address: pingping_zuo@126.com.
authors: Pingping
authors: P
authors: Zuo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000473:pathology*; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D019344:Lactic Acid; C033616:poly(lactide)
keywords: Docetaxel (DTX); Nanoparticles; Small cell lung cancer (SCLC); Targeting peptide