Tumor-targeting Drug Delivery

The drug discovery program includes tumor-specific drug delivery systems, “guided molecular missiles” in the fight against cancer. Despite the significant progress in the development of cancer detection, prevention, surgery and therapy, there is still no common cure for this disease. In addition, the long-standing problem of chemotherapy is the lack of tumor-specific treatments. Traditional chemotherapy relies on the premise that rapidly proliferating cancer cells are more likely to be killed by a cytotoxic agent. In reality, however, cytotoxic agents have very little or no specificity, which leads to systemic toxicity, causing undesirable severe side effects. Therefore, various “molecularly targeted cancer therapies” have been developed for use in specific cancers, including tumor-targeting drug delivery (TTDD). In general, a TTDD system consists of a tumor recognition moiety and a cytotoxic warhead connected through a “smart” linker to form a conjugate. When a multi-functionalized nanomaterial is used as the vehicle, a “Trojan Horse” approach becomes possible for mass delivery of cytotoxic warheads to maximize the efficacy. The Ojima Laboratory has been making an excellent progress in the novel molecular approaches to the design and discovery of “guided molecular missiles” for tumor-targeting chemotherapy.

Taxoids as Potent Cytotoxic Agents for TumorTargeting Drug Delivery

One of the key problems with conventional chemotherapy is its toxicity: In addition to its beneficial characteristics of killing cancer cells, anticancer drugs also destroy healthy tissue resulting in systemic toxicity. Improvement in the potency and anti-MDR activities of anticancer drugs has provided efficient in treatment of aggressive and resistant tumors, although systemic toxicity persists and plays an important role in overall efficacy.

A Possible solution is Tumor-Targeting Drug Delivery which combines powerful anti-cancer compounds with tumor-targeting molecules. Paul Ehrlich (14 March 1854 – 20 August 1915) was a German scientist who won the 1908 Nobel Prize in Physiology or Medicine. He is noted for his work in hematology, immunology, and chemotherapy. Ehrlich predicted autoimmunity calling it "horror autotoxicus". He coined the term “chemotherapy" and popularized the concept of a “magic bullet". He is credited with the first empirical observation of the blood-brain barrier and the development of the first antibacterial drug in modern medicine.

ImmunoGen has developed technology known as “tumor-activiated prodrugs,” (TAPs), in which the anticancer agents are linked chemically to certain types of monoclonal antibodies. Those antibodies specifically bind to antigens that are known to be expressed predominantly on the cancer cell surface. The anit-cancer drug is inactive until it enters the tumor cell to which it is targeted to by the monoclonal antibody. In this way, the anticancer drugs are exclusively delivered to the cancer cells, leaving the normal cells intact. We have designed and synthesized novel taxanes used as cytotoxic agents in TAPs. Biological assays have since shown very impressive results.


“Recent Advances in Tumor-targeting Anticancer Drug Conjugates”, S. Jaracz, J. Chen, L. V. Kuznetsova, and I. Ojima, Bioorg. Med. Chem., 13, 5043-5054 (2005)

Tumor-targeting Molecules


Jaracz, S. et al. (Ojima, I.) Bioorg. Med. Chem. 2005, 13, 5043–5054

Protein-Mediated TTM Internalization


Ojima, I. Acc. Chem. Res. 2008, 41, 108.

Chen, S., et. al. Bioconjugate Chem. 2010, 21, 979-987.

Seitz, J. D., Ojima, I. Drug Delivery in Oncology: From Basic Research to Cancer Therapy. Ed. Kratz, F., et. al. In Press

First Generation mAb-Taxoid Drug Conjugate


New Self-Immolative Linkers for Taxoid Conjugates


I. Ojima, Chem. Bio. Chem. 5, 628-635 (2004).

I. Ojima, Acc. Chem. Res. 41, 108-119 (2008).

Fluorescence-Labeled Probes


Ojima, I. Acc. Chem. Res. 2008, 41, 108.

Chen, S., et. al. Bioconjugate Chem. 2010, 21, 979-987.

Drug Release


Ojima, I. Acc. Chem. Res. 2008, 41, 108.

Chen, S., et. al. Bioconjugate Chem. 2010, 21, 979-987

Internalization and Drug Release of Biotin-CNT-Linker-Taxoid-Fluorescein


CFM images of L1210FR cells treated with biotin-CNT-taxoid-fluorescein incubated in the absence (A) and in the presence (B) of GSH Et ester. The latter shows the presence of a microtubule network, polymerized by taxoid, after the disulfide bonds had been cleaved by the GSH ethyl ester.



Advantages of CNT-based DDS:

  • Amplification of tumor-targeting drug delivery via the “enhanced permeability and retention” (EPR) effect associated with nano-scale materials.
  • Ability to exploit multivalent recognition of overexpressed receptors on the surfaces of the tumor cells.
  • Increased drug loading capacity
  • Capability of controlled drug release inside tumor cells.


J. Chen S. Chen, X. Zhao, L. Kuznetsova, S. S. Wong, I. Ojima, J. Am. Chem. Soc. 130, 16778-16785 (2008).

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Tumor-Targeting Drug Delivery

“Magic Bullet”

Department of Chemistry, Stony Brook University, Stony Brook, New York 11794-3400 Phone: (631) 632-7890