title: Simultaneous delivery of Paclitaxel and Bcl-2 siRNA via pH-Sensitive liposomal nanocarrier for the synergistic treatment of melanoma.
abstract: pH-sensitive drug carriers that are sensitive to the acidic (pH = ~6.5) microenvironments of tumor tissues have been primarily used as effective drug/gene/siRNA/microRNA carriers for releasing their payloads to tumor cells/tissues. Resistance to various drugs has become a big hurdle in systemic chemotherapy in cancer. Therefore delivery of chemotherapeutic agents and siRNA's targeting anti apoptotic genes possess advantages to overcome the efflux pump mediated and anti apoptosis-related drug resistance. Here, we report the development of nanocarrier system prepared from kojic acid backbone-based cationic amphiphile containing endosomal pH-sensitive imidazole ring. This pH-sensitive liposomal nanocarrier effectively delivers anti-cancer drug (Paclitaxel; PTX) and siRNA (Bcl-2), and significantly inhibits cell proliferation and reduces tumor growth. Tumor inhibition response attributes to the synergistic effect of PTX potency and MDR reversing ability of Bcl-2 siRNA in the tumor supporting that kojic acid based liposomal pH-sensitive nanocarrier as efficient vehicle for systemic co-delivery of drugs and siRNA.
authors: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology (IICT), Tarnaka, Hyderabad-500007, India.|Academy of Scientific and Innovative Research (AcSIR), Training and Development Complex, CSIR Campus, CSIR Road, Taramani, Chennai-600 113, India.
authors: Teegala Lakshminarayan
authors: TL
authors: Reddy
authors: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology (IICT), Tarnaka, Hyderabad-500007, India.|Academy of Scientific and Innovative Research (AcSIR), Training and Development Complex, CSIR Campus, CSIR Road, Taramani, Chennai-600 113, India.
authors: Koteswara Rao
authors: KR
authors: Garikapati
authors: Centre for Semiochemicals, CSIR-Indian Institute of Chemical Technology (IICT), Tarnaka, Hyderabad-500007, India.
authors: S Gopal
authors: SG
authors: Reddy
authors: Centre for Semiochemicals, CSIR-Indian Institute of Chemical Technology (IICT), Tarnaka, Hyderabad-500007, India.
authors: B V Subba
authors: BV
authors: Reddy
authors: Centre for Semiochemicals, CSIR-Indian Institute of Chemical Technology (IICT), Tarnaka, Hyderabad-500007, India.
authors: J S
authors: JS
authors: Yadav
authors: Functional Genomics and Gene Silencing Group, CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad-500007, India.
authors: Utpal
authors: U
authors: Bhadra
authors: Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology (IICT), Tarnaka, Hyderabad-500007, India.|Academy of Scientific and Innovative Research (AcSIR), Training and Development Complex, CSIR Campus, CSIR Road, Taramani, Chennai-600 113, India.
authors: Manika Pal
authors: MP
authors: Bhadra
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004339:Drug Compounding; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011753:Pyrones / Q000737:chemistry; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C000595707:BCL2 protein, human; D007093:Imidazoles; D008081:Liposomes; D010714:Phosphatidylethanolamines; D019253:Proto-Oncogene Proteins c-bcl-2; D011753:Pyrones; D034741:RNA, Small Interfering; C038089:1,2-distearoylphosphatidylethanolamine; C094877:dioleoyl phosphatidylethanolamine; C011890:kojic acid; C029899:imidazole; D017239:Paclitaxel