Quantum Dots for Cancer Diagnosis and Therapy: Biological and Clinical Perspectives

Hua Zhang; Douglas Yee; Chun Wang

Disclosures

Nanomedicine. 2008;3(1):83-91. 

In This Article

Future Perspective

In the next 5-10 years, we predict that the research of QDs in cancer imaging will lead to breakthroughs that enable their clinical application, especially with conjugated QDs in targeting metastasis and in quantitative measurement of molecular targets. Currently, conjugated QDs can target solid tumor tissues with mature vasculature, however, micrometastasis without well developed vasculature is difficult to detect. Therefore, the surface of QDs needs to be further engineered to enable efficient extravasation, to reach micrometastasis and initiate binding to tumor antigens. To quantify molecular targets in micrometastasis, it is difficult to establish an internal (or external) standard to rate the fluorescence intensity on tumors, which represents the level of molecular targets. One potential solution to this problem might be that, when the molecular target to be quantified (such as IGF1R) is different from the tumor antigen used for locating micrometastasis (such as MUC1), the level of molecular target can be quantified as the ratio of the fluorescent intensities between the molecular target and the tumor antigen.

In addition, the surface of QDs needs to be further refined to minimize RES uptake and maximize tumor-specific uptake. Because metastasis can happen in the RES system, especially in the liver and lymph nodes, nonspecific RES uptake will bring false-positive results. Given the fast-pace development of novel surface chemistry and engineering techniques with nanometer precision, it is very likely that this problem will be solved. QD tags will become an indispensable component of many targeted therapeutics, including inhibitory antibodies and siRNA for tracking their delivery in vivo. Recent and future progress on tracking therapeutic stem cells with QDs for treating cardiovascular diseases[60] might inspire similar efforts for tracking cell-based immunotherapy for cancer. Furthermore, long-term toxicity studies will reveal how and where QDs can be stored, degraded or released from the body. Because of their low toxicity potential, silicon QDs will probably emerge as an attractive alternative to heavy metal-containing QDs and move towards biological and clinical applications.

We envision an idealized clinical scenario in which primary tumor and metastasis are diagnosed early, followed by effective targeted treatment without the need for surgery. It will typically involve three major steps, as described below. First, antibody- or ligand-conjugated QDs that target to tumor antigens will be delivered intravenously to a patient and, through blood circulation, they reach the metastasized tumor. The position of fluorescence detected in the body will localize to the metastasis. Second, another type of conjugated QD that can measure levels of molecular targets quantitatively on the tumor cell surface will be administered either intravenously or locally near the metastatic region. Multiple types of conjugated QDs targeting distinct molecules with different fluorescent spectra can be applied simultaneously. The fluorescent intensity in the metastasis region will correlate with the level of molecular targets. Finally, targeted therapy against an overexpressed molecular target will be used on the patient to eradicate metastasis. The targeted therapeutic agents might also be tagged with QDs and, along with multiplexed quantification of the therapeutic targets, they enable oncologists to track the delivery of drugs inside the patient and monitor the efficacy of treatment noninvasively in real time.

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