Research ArticlesNanomedicine

Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile

Science Translational Medicine  04 Apr 2012:
Vol. 4, Issue 128, pp. 128ra39
DOI: 10.1126/scitranslmed.3003651

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Nanomedicine: From Mice to Men

There has been a lot of buzz surrounding nanomedicine. Yet, this word inspires more thoughts of futuristic medicine à la Star Trek than actual visions of the clinic. Indeed, despite the intense research focus on nano-based approaches to everything from cancer to neurodegenerative disease, few nanotechnologies have actually worked in humans. Bridging this obvious translational gap, Hrkach and colleagues have now designed the ideal nanoparticle for targeting and killing cancer cells not only in animals but also in humans.

The authors first created a combinatorial library of nanoparticles of varying size, polymer composition and concentration, and processing parameters. The particles contained docetaxel (DTXL), a potent chemotherapeutic, as well as a ligand that selectively targeted prostate-specific membrane antigen, which is present on the surface of prostate cancer cells and on the neovasculature of nonprostate solid tumors. Hrkach et al. showed that the optimized targeted nanoparticle (DTXL-TNP) could release anticancer drug in a controlled manner in vitro as well as in vivo in rats, without any toxicity to the animals. In a mouse model of human prostate cancer, the DTXL-TNPs were also able to slow tumor growth to 26%, whereas the free DTXL could not stop tumors from growing 100% over the 7-week study.

Hrkach and coauthors showed that the pharmacokinetic profile of DTXL-TNPs did not differ among mice, rats, and monkeys, which is an important observation when moving new drug delivery platforms from animals to humans. Indeed, their interim results from 12 cancer patients enrolled in a phase 1 clinical trial showed nanoparticle clearance over time similar to the animals. Two of these patients—one with lung metastases, one with tonsillar cancer—even showed signs of tumor shrinkage after being treated with the DTXL-TNPs. After the clinical trial is complete, we will have a better idea of whether these nanoparticles are truly effective at seeking out and killing cancer. In the meantime, we look forward to the day that “nanomedicine” is no longer a buzz word, and is instead routine clinical practice.