Abstract Title

PREPARATION OF A CISPLATIN PRODRUG FOR USE AGAINST NON-SMALL CELL LUNG CANCER

Presenter Name

Warren Redfearn

Abstract

Background: Lung cancer is the leading cause of cancer-related death in the United States, and non-small cell lung cancer (NSCLC) the most common type. NSCLC is extremely difficult to treat, resulting in a poor prognosis for patients. Platinum (Pt) anti-cancer agents, such as cisplatin, remain a mainstay in the clinic; however, these Pt complexes act nonspecifically, and thus result in serious side-effects. Development and delivery of a Pt complex with an improved therapeutic index would be highly advantageous to the fight against NSCLC. We prepared trans, cis, cis-bis(heptanoato)amine(cyclohexylamine)dichloridoplatinum(IV), referred to here as PtC, and studied its DNA binding and toxicity toward normal lung and NSCLC cells.

Methods: A lipophilic Pt(IV) complex, PtC, was synthesized and characterized, and its binding to DNA and toxicity toward various cancer and normal cell lines determined. Results: We confirmed that the synthesized Pt complex binds to DNA in a manner similar to that of cisplatin, which suggests that it is cisplatin prodrug; however, probably due to its lipophilic nature and improved stability, PtC is much more toxic toward NSCLC cell lines than is cisplatin, and has a much improved therapeutic index. Conclusions: PtC shows promise as a therapeutic agent against NSCLC, and, furthermore, its lipophilic nature allows for us to incorporate it into mesoporous silica nanoparticles for fine-controlled release and the targeting of tumors.

Presentation Type

Poster

Purpose (a):

Lung cancer is the leading cause of cancer-related death in the United States, and non-small cell lung cancer (NSCLC) the most common type. NSCLC is extremely difficult to treat, resulting in a poor prognosis for patients. Platinum (Pt) anti-cancer agents, such as cisplatin, remain a mainstay in the clinic; however, these Pt complexes act nonspecifically, and thus result in serious side-effects. Development and delivery of a Pt complex with an improved therapeutic index would be highly advantageous to the fight against NSCLC. We prepared trans, cis, cis-bis(heptanoato)amine(cyclohexylamine)dichloridoplatinum(IV), referred to here as PtC, and studied its DNA binding and toxicity toward normal lung and NSCLC cells.

Methods (b):

A lipophilic Pt(IV) complex, PtC, was synthesized and characterized, and its binding to DNA and toxicity toward various cancer and normal cell lines determined.

Results (c):

We confirmed that the synthesized Pt complex binds to DNA in a manner similar to that of cisplatin, which suggests that it is cisplatin prodrug; however, probably due to its lipophilic nature and improved stability, PtC is much more toxic toward NSCLC cell lines than is cisplatin, and has a much improved therapeutic index.

Conclusions (d):

PtC shows promise as a therapeutic agent against NSCLC, and, furthermore, its lipophilic nature allows for us to incorporate it into mesoporous silica nanoparticles for fine-controlled release and the targeting of tumors.

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PREPARATION OF A CISPLATIN PRODRUG FOR USE AGAINST NON-SMALL CELL LUNG CANCER

Background: Lung cancer is the leading cause of cancer-related death in the United States, and non-small cell lung cancer (NSCLC) the most common type. NSCLC is extremely difficult to treat, resulting in a poor prognosis for patients. Platinum (Pt) anti-cancer agents, such as cisplatin, remain a mainstay in the clinic; however, these Pt complexes act nonspecifically, and thus result in serious side-effects. Development and delivery of a Pt complex with an improved therapeutic index would be highly advantageous to the fight against NSCLC. We prepared trans, cis, cis-bis(heptanoato)amine(cyclohexylamine)dichloridoplatinum(IV), referred to here as PtC, and studied its DNA binding and toxicity toward normal lung and NSCLC cells.

Methods: A lipophilic Pt(IV) complex, PtC, was synthesized and characterized, and its binding to DNA and toxicity toward various cancer and normal cell lines determined. Results: We confirmed that the synthesized Pt complex binds to DNA in a manner similar to that of cisplatin, which suggests that it is cisplatin prodrug; however, probably due to its lipophilic nature and improved stability, PtC is much more toxic toward NSCLC cell lines than is cisplatin, and has a much improved therapeutic index. Conclusions: PtC shows promise as a therapeutic agent against NSCLC, and, furthermore, its lipophilic nature allows for us to incorporate it into mesoporous silica nanoparticles for fine-controlled release and the targeting of tumors.