Posted December 30, 2013
Subhash C. Chauhan, Ph.D.
Advanced stage prostate cancer is largely untreatable with current therapies, indicating a strong need for improved prostate cancer treatment. Radioimmunotherapy (RIT) is a rapidly emerging therapeutic modality for the treatment of a wide variety of cancers. However, so far, in solid tumors such as prostate cancer, RIT has shown only partial success both in preclinical and clinical studies. The partial response of RIT in solid tumors is primarily due to reduced accessibility of radio-probes to the cancer cells and their inferior radio-sensitivity. Another therapeutic agent already under investigation for various cancer types of all stages, called curcumin, is also known for inducing radio-sensitization/chemo-sensitization in cancer cells. Taking advantage of this powerful pre-existing agent, a team of investigators at the Sanford Research/University of South Dakota, led by Dr. Subhash C. Chauhan*, a FY07 PCRP New Investigator Award recipient, has undertaken a challenge to develop a novel therapy that combines nanotechnology with the unique aspects of both RIT and curcumin. The team has investigated the hypothesis that loading curcumin into nanoparticles (NPs) created to specifically target prostate cancer cells via an anti-PSMA antibody will improve the effectiveness of treatment due to tumor cell uptake of the NP-antibody complex.
Dr. Chauhan's team has made significant progress to date towards their goal of developing a PSMA-targeted curcumin nanoparticle modality. First, they started by generating a biodegradable controlled drug delivery carrier, called nano-curcumin, using poly(lactic-co-glycolic acid) (PLGA). They found that this nano-curcumin formulation exhibits a higher therapeutic efficacy in cell proliferation and colony formation assays, and in a xenograft mouse model. The team then proceeded to add the anti-PSMA antibody to the curcumin-loaded nanoparticles; they have been able to demonstrate efficient and reproducible chemistry for this new conjugate particle, and biodistribution experiments indicate that the PSMA-targeted particles have an enhanced tumor specific accumulation. Additionally, Dr. Chauhan's team has developed additional curcumin nanoparticles for imaging and treatment of prostate cancer, called multifunctional magnetic nanoparticles (MNPs). This novel and multifunctional MNP formulation has been patented and published. Dr. Chauhan's studies to date support the feasibility and efficacy of an innovative nano-radio-immunotherapeutic (Nano-RIT) approach for advanced prostate cancer treatment.
*Dr. Chauhan's lab is now located at the University of Tennessee Health Science Center in Memphis, TN
- Yallapu MM, Ebeling M, Khan S, Sundram V, Chauhan N, Gupta BK, Puumala SE, Jaggi M, Chauhan SC. Novel Curcumin Loaded Magnetic Nanoparticles for Pancreatic Cancer Treatment. Mol Cancer Ther 2013 [Epub ahead of print] PMID 23704793
- Yallapu MM, Othman SF, Curtis ET, Bauer NA, Chauhan N, Kumar D, Jaggi M, Chauhan SC. Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications. Int J Nanomedicine. 2012; 7: 1761-79. PMID: 22619526; PMCID: PMC3356199
- Yallapu MM., Othman SF., Curtis ET., Gupta B., Jaggi M and Chauhan SC. Multi-functional Magnetic Nanoparticles for Magnetic Resonance Imaging and Cancer Therapy. Biomaterials 2011; 32(7): 1890-1905 PMID: 21167595; PMCID: PMC3021632
- Yallapu MM., Gupta B., Jaggi M and Chauhan SC*. Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells. Journal of Colloid & Interface Science 2010,1;351(1):19-29. (Cover illustration). PMID: 20627257