title: Improved breast cancer cell-specific intracellular drug delivery and therapeutic efficacy by coupling decoration with cell penetrating peptide and SP90 peptide.
abstract: Lack of satisfactory specificity towards tumor cells and poor intracellular delivery efficacy are the major drawbacks with conventional cancer chemotherapy. Conjugated anticancer drugs to targeting moieties e.g. to peptides with the ability to recognize cancer cells and to cell penetrating peptide can improve these characteristics, respectively. Combining a tumor homing peptide with an appropriate cell-penetrating peptide can enhance the tumor-selective internalization efficacy of the carrying cargo molecules. In the present study, the breast cancer homing ability of SP90 peptide and the synergistic effect of SP90 with a cell-penetrating peptide(C peptide) were evaluated. SP90 and chimeric peptide SP90-C specifically targeted cargo molecule into breast cancer cells, especially triple negative MDA-MB-231 cell, in a dose- and time-dependent manner, but not normal breast cells and other cancer cells, while C peptide alone had no cell-selectivity. SP90-C increased the intracellular delivery efficiency by 12-fold or 10-fold compared to SP90 or C peptide alone, respectively. SP90 and SP90-C conjugation increased the anti-proliferative and apoptosis-inducing activity of HIV-1 Vpr, a potential novel anticancer protein drug, to breast cancer cell but not normal breast cell by arresting cells in G2/M phase. With excellent breast cancer cell-selective penetrating efficacy, SP90-C appears as a promising candidate vector for targeted anti-cancer drug delivery. SP90-VPR-C is a potential novel breast cancer-targeted anticancer agent for its high anti-tumor activity and low toxicity.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China. Electronic address: fanglq@ecust.edu.cn.
authors.forename: Li-Qiang
authors.initials: LQ
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Guo-Xiu
authors.initials: GX
authors.lastname: Du
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Li
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013997:Time Factors; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C000614100:SP90 peptide; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1
keywords: Breast cancer therapy; Cell-penetrating peptide; Homing peptide; Targeted drug delivery; VPR