Facile, efficient approach to accomplish tunable chemistries and variable biodistributions for shell cross-linked nanoparticles.
The in vivo behavior of shell cross-linked knedel-like (SCK) nanoparticles is shown to be tunable via a straightforward and versatile process that advances SCKs as attractive nanoscale carriers in the field of nanomedicine. Tuning of the pharmacokinetics was accomplished by grafting varied numbers of methoxy-terminated poly(ethylene glycol) (mPEG) chains to the amphiphilic block copolymer precursors, together with chelators for the radioactive tracer and therapeutic agent (64)Cu, followed by self-assembly into block copolymer micelles and chemical cross-linking throughout the shell regions. (64)Cu-radiolabeling was then performed to evaluate the SCKs in vivo by means of biodistribution experiments and positron emission tomography (PET). It was found that the blood retention of PEGylated SCKs could be tuned, depending on the mPEG grafting density and the nanoparticle surface properties. A semiquantitative model of the density of mPEG surface coverage as a function of in vivo behavior was applied to enhance the understanding of this system.
Department of Chemistry, Washington University in Saint Louis, Saint Louis, Missouri 63130, USA.
Guorong
G
Sun
Aviv
A
Hagooly
Jinqi
J
Xu
Andreas M
AM
Nyström
Zicheng
Z
Li
Raffaella
R
Rossin
Dennis A
DA
Moore
Karen L
KL
Wooley
Michael J
MJ
Welch
D000818:Animals; D001682:Biological Availability; D001769:Blood; D003301:Copper Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D005260:Female; D008823:Micelles; D009132:Muscles; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley
D003301:Copper Radioisotopes; D008823:Micelles; D011108:Polymers; D019275:Radiopharmaceuticals; D011092:Polyethylene Glycols