Nanoparticle (NP)-based drug delivery platforms have received a great deal of attention over the past two decades for their potential in targeted cancer therapies. Despite the promises, passive targeting approaches utilizing relatively larger NPs (typically 50-200 nmin diameter) allow for passive tumor accumulation, but hinder efficient intratumoral penetration. Conversely, smaller, actively targeted NPs (<20nmin diameter) penetrate well into the tumor mass, but are limited by their rapid systemic elimination. To overcome these limitations, we have designed amulti-scale hybrid NP platformthat loads smaller poly(amidoamine) (PAMAM) dendrimers (∼5 nm in diameter) into larger poly(ethylene glycol)-b-poly(D,L-lactide) (PEG-PLA) NPs (∼70 nm). A biodistribution study in healthy mice revealed that the hybrid NPs circulated longer than free dendrimers and were mostly cleared by macrophages in the liver and spleen, similar to the in vivo behavior of PEG-PLA NPs. When injected intravenously into the BALB/c athymic nude mice bearing folate receptor (FR)-overexpressing KB xenograft, the targeted hybrid NPs encapsulating folate (FA)-targeted dendrimers achieved longer plasma circulation than free dendrimers and higher tumor concentrations than both free dendrimers and the empty PEG-PLA NPs. These results suggest that the hybrid NPs successfully combine the in vivo advantages of dendrimers and polymeric NPs, demonstrating their potential as a new, modular platform for drug delivery.
Bibliographical noteFunding Information:
This work was supported by the Hans W. Vahlteich Research Fund from the University of Illinois at Chicago (UIC) and the UIC Chancellor's Multidisciplinary Discovery Fund . The research was conducted in a facility constructed with support from the NIH (grant# C06RR15482 ). The authors thank Ms. Eri Iwasaki for her assistance in the animal studies.
All Science Journal Classification (ASJC) codes
- Pharmaceutical Science