In vitro demonstration of enhanced prostate cancer toxicity: pretargeting with Bombesin bispecific complexes and targeting with polymer-drug-conjugates

Autor:	Stan Majewski, Ban-An Khaw, Vishwesh Patil, Rajiv Panwar, Alexandra D. Varvarigou, Yared Tekabe, Keyur Gada
Rok vydání:	2013
Předmět:	Male Pharmaceutical Science Enhanced permeability and retention effect Pharmacology Cell Line chemistry.chemical_compound Inhibitory Concentration 50 Drug Delivery Systems Cell Line Tumor Antibodies Bispecific polycyclic compounds medicine Animals Humans Doxorubicin Myocytes Cardiac Pretargeting Polymer-drug conjugates Drug Carriers Antibiotics Antineoplastic organic chemicals Bombesin Prostatic Neoplasms Pentetic Acid Bombesin receptor Rats Receptors Bombesin chemistry Polyglutamic Acid Toxicity Cancer cell medicine.drug
Zdroj:	Journal of drug targeting. 21(10)
ISSN:	1029-2330
Popis:	Bombesin has been used to target Bombesin receptor, a growth receptor, which is over-expressed in many cancers, including prostate cancer. Polymer-anti-neoplastic-drug-conjugates (PDC) were also developed to reduce non-specific toxicity and increase tumor toxicity utilizing the enhanced permeability and retention effect, benefitting treatment of large tumors with well-established vasculature.If PDCs were delivered by targeted delivery to cancer cells, tumor toxicity would be enhanced and non-specific toxicity decreased.Cardiocyte toxicity was assessed in H9c2 cardiocytes with doxorubicin (Dox) or N-terminal DTPA-modified-Doxorubicin-loaded-polyglutamic acid polymers (D-Dox-PGA). Therapeutic efficacy of targeted D-Dox-PGA after pretargeting with Bombesin-conjugated anti-DTPA-antibody Bispecific Complexes (Bom-BiSpCx) was compared to that of Dox in PC3 cells. Bom-BiSpCx was generated by thioether bond between Bombesin to Anti-DTPA antibody.D-Dox-PGA was demonstrated to have less cardiocyte toxicity (IC50 = 20 µg/ml) than free Dox (1.55 µg/ml, p0.001). However, after pre-targeting of human prostate cancer PC3 cells with Bom-BiSpCx and targeting with D-Dox-PGA, IC50 (13.2 µg/ml) was about two times less than that of Dox (28.5 µg/ml, p0.0001).Targeted delivery of PDCs having lower cardiocyte toxicity enabled higher efficiency cancer cell therapy.This study may allow development of very efficient targeted prostate cancer pro-drug therapy.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f0e663114f7c9a0d6d4696cb273a0eb5 https://pubmed.ncbi.nlm.nih.gov/23863118 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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