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Discovery of peptide drug carrier candidates for targeted multi-drug delivery into prostate cancer cells

Metastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliv... Full description

Journal Title: Cancer letters 2017-11-01, Vol.408, p.164-173
Main Author: Bashari, O
Other Authors: Redko, B , Cohen, A , Luboshits, G , Gellerman, G , Firer, M.A
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Ireland: Elsevier B.V
ID: ISSN: 0304-3835
Link: https://www.ncbi.nlm.nih.gov/pubmed/28888997
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title: Discovery of peptide drug carrier candidates for targeted multi-drug delivery into prostate cancer cells
format: Article
creator:
  • Bashari, O
  • Redko, B
  • Cohen, A
  • Luboshits, G
  • Gellerman, G
  • Firer, M.A
subjects:
  • Antigens
  • Antineoplastic Agents - administration & dosage
  • Antineoplastic Agents - pharmacology
  • Apoptosis - drug effects
  • Bacteriophages - metabolism
  • Camptothecin
  • Cancer
  • Cancer cells
  • Cancer therapies
  • Castration
  • Cell Proliferation - drug effects
  • Chemotherapy
  • Chlorambucil
  • Cloning
  • Conjugation
  • Criteria
  • Current carriers
  • Cytotoxicity
  • Drug carriers
  • Drug Carriers - chemistry
  • Drug combination
  • Drug delivery
  • Drug Delivery Systems
  • Drug resistance
  • Drug therapy
  • Drug therapy, Combination
  • Drugs
  • Evolution & development
  • Humans
  • Immunoglobulins
  • Libraries
  • Ligands
  • Male
  • Metastases
  • Metastasis
  • Patients
  • Peptide
  • Peptide Fragments - administration & dosage
  • Peptide Fragments - pharmacology
  • Peptide Library
  • Peptide-drug-conjugate
  • Peptides
  • Phage display
  • Phages
  • Pituitary hormones
  • Prostate
  • Prostate cancer
  • Prostatic Neoplasms - drug therapy
  • Prostatic Neoplasms - metabolism
  • Prostatic Neoplasms - pathology
  • Studies
  • Synergistic effect
  • Targeted drug delivery
  • Tumor Cells, Cultured
  • Tumors
  • Vehicles
ispartof: Cancer letters, 2017-11-01, Vol.408, p.164-173
description: Metastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells. Phage from a libraries displaying 7mer peptides were exposed to PC-3 cells and only internalized phage were recovered. The ability of these phage to internalize into other prostate cancer cells (LNCaP, DU-145) was validated. The displayed peptides of selected phage clones were synthesized and their specificity for target cells was validated in vitro and in vivo. One peptide (P12) which specifically targeted PC-3 tumors in vivo was incorporated into mono-drug (Chlorambucil, Combretastatin or Camptothecin) and dual-drug (Chlorambucil/Combretastatin or Chlorambucil/Camptothecin) PDCs and the cytotoxic efficacy of these conjugates for target cells was tested. Conjugation of P12 into dual-drug PDCs allowed discovery of new drug combinations with synergistic effects. The use of strict selection criteria can lead to discovery of novel peptides for use as drug carriers for TDD. PDCs represent an effective alternative to current modes of free drug chemotherapy for prostate cancer. •Criteria are used to isolate cell targeting peptides from phage display libraries.•Peptides were internalized by different prostate cancer cells.•One selected peptide was used to prepare multi-drug peptide-drug-conjugates.•Multi-drug peptide-drug-conjugates can produce novel synergistic cytotoxicities.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0304-3835
fulltext: fulltext
issn:
  • 0304-3835
  • 1872-7980
url: Link


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creatorBashari, O ; Redko, B ; Cohen, A ; Luboshits, G ; Gellerman, G ; Firer, M.A
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descriptionMetastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells. Phage from a libraries displaying 7mer peptides were exposed to PC-3 cells and only internalized phage were recovered. The ability of these phage to internalize into other prostate cancer cells (LNCaP, DU-145) was validated. The displayed peptides of selected phage clones were synthesized and their specificity for target cells was validated in vitro and in vivo. One peptide (P12) which specifically targeted PC-3 tumors in vivo was incorporated into mono-drug (Chlorambucil, Combretastatin or Camptothecin) and dual-drug (Chlorambucil/Combretastatin or Chlorambucil/Camptothecin) PDCs and the cytotoxic efficacy of these conjugates for target cells was tested. Conjugation of P12 into dual-drug PDCs allowed discovery of new drug combinations with synergistic effects. The use of strict selection criteria can lead to discovery of novel peptides for use as drug carriers for TDD. PDCs represent an effective alternative to current modes of free drug chemotherapy for prostate cancer. •Criteria are used to isolate cell targeting peptides from phage display libraries.•Peptides were internalized by different prostate cancer cells.•One selected peptide was used to prepare multi-drug peptide-drug-conjugates.•Multi-drug peptide-drug-conjugates can produce novel synergistic cytotoxicities.
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1EISSN: 1872-7980
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3PMID: 28888997
languageeng
publisherIreland: Elsevier B.V
subjectAntigens ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Bacteriophages - metabolism ; Camptothecin ; Cancer ; Cancer cells ; Cancer therapies ; Castration ; Cell Proliferation - drug effects ; Chemotherapy ; Chlorambucil ; Cloning ; Conjugation ; Criteria ; Current carriers ; Cytotoxicity ; Drug carriers ; Drug Carriers - chemistry ; Drug combination ; Drug delivery ; Drug Delivery Systems ; Drug resistance ; Drug therapy ; Drug therapy, Combination ; Drugs ; Evolution & development ; Humans ; Immunoglobulins ; Libraries ; Ligands ; Male ; Metastases ; Metastasis ; Patients ; Peptide ; Peptide Fragments - administration & dosage ; Peptide Fragments - pharmacology ; Peptide Library ; Peptide-drug-conjugate ; Peptides ; Phage display ; Phages ; Pituitary hormones ; Prostate ; Prostate cancer ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Studies ; Synergistic effect ; Targeted drug delivery ; Tumor Cells, Cultured ; Tumors ; Vehicles
ispartofCancer letters, 2017-11-01, Vol.408, p.164-173
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descriptionMetastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells. Phage from a libraries displaying 7mer peptides were exposed to PC-3 cells and only internalized phage were recovered. The ability of these phage to internalize into other prostate cancer cells (LNCaP, DU-145) was validated. The displayed peptides of selected phage clones were synthesized and their specificity for target cells was validated in vitro and in vivo. One peptide (P12) which specifically targeted PC-3 tumors in vivo was incorporated into mono-drug (Chlorambucil, Combretastatin or Camptothecin) and dual-drug (Chlorambucil/Combretastatin or Chlorambucil/Camptothecin) PDCs and the cytotoxic efficacy of these conjugates for target cells was tested. Conjugation of P12 into dual-drug PDCs allowed discovery of new drug combinations with synergistic effects. The use of strict selection criteria can lead to discovery of novel peptides for use as drug carriers for TDD. PDCs represent an effective alternative to current modes of free drug chemotherapy for prostate cancer. •Criteria are used to isolate cell targeting peptides from phage display libraries.•Peptides were internalized by different prostate cancer cells.•One selected peptide was used to prepare multi-drug peptide-drug-conjugates.•Multi-drug peptide-drug-conjugates can produce novel synergistic cytotoxicities.
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1Antineoplastic Agents - administration & dosage
2Antineoplastic Agents - pharmacology
3Apoptosis - drug effects
4Bacteriophages - metabolism
5Camptothecin
6Cancer
7Cancer cells
8Cancer therapies
9Castration
10Cell Proliferation - drug effects
11Chemotherapy
12Chlorambucil
13Cloning
14Conjugation
15Criteria
16Current carriers
17Cytotoxicity
18Drug carriers
19Drug Carriers - chemistry
20Drug combination
21Drug delivery
22Drug Delivery Systems
23Drug resistance
24Drug therapy
25Drug therapy, Combination
26Drugs
27Evolution & development
28Humans
29Immunoglobulins
30Libraries
31Ligands
32Male
33Metastases
34Metastasis
35Patients
36Peptide
37Peptide Fragments - administration & dosage
38Peptide Fragments - pharmacology
39Peptide Library
40Peptide-drug-conjugate
41Peptides
42Phage display
43Phages
44Pituitary hormones
45Prostate
46Prostate cancer
47Prostatic Neoplasms - drug therapy
48Prostatic Neoplasms - metabolism
49Prostatic Neoplasms - pathology
50Studies
51Synergistic effect
52Targeted drug delivery
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54Tumors
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abstractMetastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells. Phage from a libraries displaying 7mer peptides were exposed to PC-3 cells and only internalized phage were recovered. The ability of these phage to internalize into other prostate cancer cells (LNCaP, DU-145) was validated. The displayed peptides of selected phage clones were synthesized and their specificity for target cells was validated in vitro and in vivo. One peptide (P12) which specifically targeted PC-3 tumors in vivo was incorporated into mono-drug (Chlorambucil, Combretastatin or Camptothecin) and dual-drug (Chlorambucil/Combretastatin or Chlorambucil/Camptothecin) PDCs and the cytotoxic efficacy of these conjugates for target cells was tested. Conjugation of P12 into dual-drug PDCs allowed discovery of new drug combinations with synergistic effects. The use of strict selection criteria can lead to discovery of novel peptides for use as drug carriers for TDD. PDCs represent an effective alternative to current modes of free drug chemotherapy for prostate cancer. •Criteria are used to isolate cell targeting peptides from phage display libraries.•Peptides were internalized by different prostate cancer cells.•One selected peptide was used to prepare multi-drug peptide-drug-conjugates.•Multi-drug peptide-drug-conjugates can produce novel synergistic cytotoxicities.
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doi10.1016/j.canlet.2017.08.040
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