Achieving efficient drug delivery is challenging in most cancers due to the nonspecific and cytotoxic nature of common chemotherapeutics. Nanoparticle-based drug delivery systems have emerged as a promising area of research to improve upon existing methods by enhancing the efficacy of cancer treatment regimens. Gold nanoparticles (AuNPs) are well suited for cancer nanotechnology as their size (~20 nm) allows prolonged circulation and accumulation at tumor sites through passive targeting[MO1] . In addition, AuNPs can also actively target the tumor cells through appropriate modification with antibody fragments. Polymer-based dendronized systems have been shown to be another effective drug delivery platform due to the ability to covalently and noncovalent deliver chemotherapeutic drugs. This project will focus on combining the advantages of gold nanoparticles and dendronized systems into a single drug delivery platform. The synthesis of dendronized gold nanoparticles will allow for targeted drug delivery in the treatment of prostate cancer and was the focus of this work.<br/> <br/>The specific aims of this work include: (i) synthesis and conjugation of poly(propylene imine)-based dendrons to doxorubicin (PPI-DOX) via acid-sensitive hydrazone bonds; (ii) synthesis of PPI-based dendrons containing antibody fragments (PPI-Ab) for active targeting of prostate cancer; and (iii) assembly of PPI-DOX and PPI-Ab dendrons onto ~20 nm gold nanoparticles. PPI dendrons are an ideal system for chemotherapeutic drug delivery because of their ease of synthesis and inherent proton-sponge effect. We have functionalized generation 2 and 3 PPI dendrons with either doxorubicin or an antibody fragment targeting the EphA2 receptor. Doxorubicin is conjugated to the PPI dendron via acid-sensitive hydrazone linkage. Incorporation of PPI-DOX and PPI-Ab dendrons onto the surface of gold nanoparticles will allow for targeted delivery of doxorubicin to prostate cancer cells, highlighting their utility as a drug delivery platform. This work will summarize recent progress towards the synthesis and characterization of dendronized gold nanoparticles for targeted drug delivery to prostate cancer cells.

Poly(propylene imine) dendronized gold nanoparticles for targeted drug delivery in prostate cancer

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.