title: Cooperative Treatment of Metastatic Breast Cancer Using Host-Guest Nanoplatform Coloaded with Docetaxel and siRNA.
abstract: Conventional chemotherapy shows moderate efficiency against metastatic cancer since it targets only part of the mechanisms regulating tumor growth and metastasis. Here, gold nanorod (GNR)-based host-guest nanoplatforms loaded with docetaxel (DTX) and small interfering RNA (siRNA)-p65 (referred to as DTX-loaded GNR (GDTX)/p65) for chemo-, RNA interference (RNAi), and photothermal ablation (PTA) cooperative treatment of metastatic breast cancer are reported. To prepare the nanoplatform, GNRs are first coated with cyclodextrin (CD)-grafted polyethylenimine (PEI) and then loaded with DTX and siRNA through host-guest interaction with CD and electrostatic interaction with PEI, respectively. Upon near-infrared laser irradiation, GNRs generate a significant hyperthermia effect to trigger siRNA and DTX release. DTX reduces tumor growth by inhibiting mitosis of cancer cells. Meanwhile, siRNA-p65 suppresses lung metastasis and proliferation of cancer cells by blocking the nuclear factor kappa B (NF-κB) pathway and downregulating the downstream genes matrix metalloproteinase-9 (MMP-9) and B cell lymphoma-2 (Bcl-2). It is demonstrated that GDTX/p65 in combination with laser irradiation significantly inhibits the growth and lung metastasis of 4T1 breast tumors. The antitumor results suggest promising potential of the host-guest nanoplatform for combinational treatment of metastatic cancer by using RNAi, chemotherapy, and PTA.
authors.affiliation: State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Dangge
authors.initials: D
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China.
authors.forename: Zhiai
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Feng
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Chengyue
authors.initials: C
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004705:Endocytosis; D005260:Female; D055785:Gene Knockdown Techniques; D006046:Gold; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D055672:Static Electricity; D043823:Taxoids / Q000627:therapeutic use*; D013696:Temperature; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; D043823:Taxoids; D000077143:Docetaxel; D006046:Gold
keywords: RNA interference; breast cancer; chemotherapy; gold nanorods; host-guest interactions