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In Situ Temperature-Jump Dynamic Nuclear Polarization: Enhanced Sensitivity in Two Dimensional ¹³C−¹³C Correlation Spectroscopy in Solution

Chan-Gyu Joo, Andrew Casey, Christopher J. Turner, and Robert G. Griffin*

Francis Bitter Magnet Laboratory and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Dynamic nuclear polarization is combined with temperature-jump methods to develop a new 2D ¹³C−¹³C NMR experiment that yields a factor of 100−170 increase in sensitivity. The polaization step is performed at ~100 K, and the sample is subsequently melted with a 10.6 μm laser pulse to yield a sample with highly polarized ¹³C spins. ¹³C detected 2D ¹³C−¹³C spectroscopy is performed in the usual manner. Click here to read full text

Click here to read cover story in Chemical and Engineering News

Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA–PEGnanoparticles
Shanta Dhara^a, Frank X. Gub^b,c,, Robert Langer^b,c,d,e, Omid C. Farokhzad^c,f,1, and Stephen J. Lippard^a,d,1

Departments of ^aChemistry and ^bChemical Engineering, ^cMIT-Harvard Center for Cancer Nanotechnology Excellence, ^dKoch Institute for Integrative Cancer Research, and ^eDivision of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139; and ^fDepartment of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115

Cisplatin is used to treat a variety of tumors, but intrinsic and acquired resistance limit its application in many types of cancer including prostate. We report here a unique strategy to deliver cisplatin to prostate cancer cells by constructing Pt(IV)-encapsulated prostate-specific membrane antigen (PSMA) targeted nanoparticles (NPs) of poly(D,L-lactic-co-glycolic acid) (PLGA)-poly(ethylene glycol) (PEG)-functionalized controlled release polymers. By using PLGA-b-PEG nanoparticles with PSMA targeting aptamers (Apt) on the surface as a vehicle for the platinum(IV) compound c,c,t [Pt(NH₃)₂(O₂CCH₂CH₂CH₂CH₂CH₃)₂Cl₂] (1), a lethal dose of cisplatin was delivered specifically to prostate cancer cells. PSMA aptamer targeted delivery of Pt(IV) cargos to PSMA+ LNCaP prostate cancer cells by endocytosis of the nanoparticle vehicles was demonstrated using fluorescence microscopy by the colocalization of green fluorescent labeled cholesterol-encapsulated NPs and the early endosome marker EEA-1. Release of cisplatin from the polymeric nanoparticles following reduction of 1 and formation of cisplatin 1,2-intrastrand d(GpG) cross-links on nuclear DNA was confirmed by using a monoclonal antibody for the adduct. A comparison between the cytotoxic activities of Pt(IV)-encapsulated PLGA-b-PEG NPs with the PSMA aptamer on the surface (Pt-NP-Apt), cisplatin, and the non-targeted Pt(IV)-encapsulated NPs (Pt-NP) against human prostate PSMA-overexpressing LNCaP and PSMA- PC3 cancer cells revealed significant differences between the three agents. Most importantly, the effectiveness of the PSMA targeted Pt-NP-Apt nanoparticles against the PSMA+ LNCaP cells is approximately an order of magnitude greater than that of free cisplatin. Click here to read publication.