Image-guided drug delivery refers to the combination of drug targeting and imaging. Preclinically, image-guided drug delivery can be used for several different purposes, e.g. for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy. (Expert Opin Drug Deliv. 2015 Aug; 12(8): 1203)
1. Nanotherapeutics - Harvard Dot (H-Dot)
Advances in molecular imaging modalities have accelerated the diagnosis and treatment of human diseases. However, tumors less than 1 cm in size still remain difficult to localize by conventional means because of the difficulty in specific targeting/delivery to the tumor site. Furthermore, high nonspecific uptake in the major organs and persistent background retention results in low tumor-to-background ratio. To overcome these issues, we have developed nonsticky and renal clearable theranostic nanoparticles (a.k.a. H-Dots). H-Dots not only target GIST for image-guided surgery, but also tailor the fate of anticancer drugs such as imatinib (IM) to the tumor site resulting in efficient treatment of unresectable GIST. In addition, H-Dots can monitor targetability, pharmacokinetics, and drug delivery, while also showing therapeutic efficacy in GIST-bearing xenograft mice following surgical resection. More importantly, IM loaded H-Dots exhibit lower uptake into the immune system, improved tumor selectivity, and increased tumor suppression compared to free IM, which accumulates in the spleen/liver. Precisely designed H-Dots can be used as a promising theranostic nanoplatform that can potentially reduce the side effects of conventional chemotherapies.
2. Chelation Therapy – Renal Clearable Nanochelators
Iron is an essential nutrient metal, but excess iron is toxic due to increased oxidative stress caused by iron-catalyzed reactive oxygen species. Although several iron chelators are clinically used to reduce iron burden, the use of these chelators is limited due to significant adverse effects likely due to nonspecific distribution of chelators in off-target tissues. To overcome this challenge, we developed iron chelator-coated ultrasmall nanochelators that can capture iron from plasma without distributing into non-target tissues and leave the body through urinary excretion. Our renal clearable nanochelators can decrease iron burden and reduce the risk of iron-mediated organ toxicity, with no overt chelator-related side effects.
- Kang H, Hu S, Cho MH, Hong SH, Choi Y, Choi HS. Theranostic nanosystems for targeted cancer therapy 2018; 23:59-72. PMID: 31186672.
- Kang H, Gravier J, Bao K, Wada H, Lee JH, Baek Y, El Fakhri G, Gioux S, Rubin BP, Coll JL, Choi HS. Renal clearable organic nanocarriers for bioimaging and drug delivery 2016;28(37):8162-8. PMID: 27414255.
- Kang H, Han M, Xue J, Baek Y, Chang J, Hu S, Nam H, Jo MJ, Fakhri GE, Hutchens MP, Choi HS, Kim J. Renal clearable nanochelators for iron overload therapy. Nat Commun. 2019;10(1):5134. PMID: 31723130.
- Kang H, Rho S, Stiles WR, Hu S, Baek Y, Hwang DW, Kashiwagi S, Kim MS, Choi HS. Size‐Size-dependent EPR effect of polymeric nanoparticles on tumor targeting Adv Healthc Mater. 2020;9(1):1901223. PubMed PMID: 31794153
- Kang H, Stiles WR, Baek Y, Nomura S, Bao K, Hu S, Park GK, Jo MJ, I H, Coll J-L, Rubin BP, Choi HS. Renal Clearable Theranostic Nanoplatforms for Gastrointestinal Stromal Tumors. Adv Mater. 2020;32(6):1905899. PubMed PMID: 31854033
Leader: Homan Kang, Ph.D., Instructor