Doxorubicin-conjugated quantum dots to target alveolar macrophages and inflammation.
The ability to provide targeted therapeutic delivery in the lung would be a major advancement in pharmacological treatments for many pulmonary diseases. Critical issues for such successful delivery would require the ability to target specific cell types, minimize toxicity (e.g., inflammatory response), and deliver therapeutic levels of drugs. We report here on the ability of nanoconjugates of CdSe/CdS/ZnS quantum dots (QDs) and doxorubicin (Dox) to target alveolar macrophages (aMØs), cells that play a critical role in the pathogenesis of inflammatory lung injuries. Confocal imaging showed the release of Dox from the QD-Dox nanoconjugate, as was evident by its accumulation in the cell nucleus and induction of apoptosis, implying that the drug retains its bioactivity after coupling to the nanoparticle. Inflammatory injury parameters (albumin leakage, proinflammatory cytokines, and neutrophil infiltration) were recorded after in vivo administration of QD-Dox and Dox, observing no significant effect after QD-Dox treatment compared with Dox. These results demonstrate that nanoparticle platforms can provide targeted macrophage-selective therapy for the treatment of pulmonary disease.


BACKGROUND
Pulmonary inflammatory diseases still often remain challenging to treat, despite decades of advances and several available agents. In this study, a quantum dot-based alveolar delivery system is presented, targeting macrophages with doxorubicin.
Chakravarthy
Krishnan V
KV
Department of Microbiology and Immunology, State University of New York at Buffalo, Buffalo, New York, USA.
Davidson
Bruce A
BA
Helinski
Jadwiga D
JD
Ding
Hong
H
Law
Wing-Cheung
WC
Yong
Ken-Tye
KT
Prasad
Paras N
PN
Knight
Paul R
PR
D000818:Animals; D018893:Bronchoalveolar Lavage; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007249:Inflammation / Q000188:drug therapy*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D016676:Macrophages, Alveolar / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D045663:Quantum Dots; D051381:Rats; D020318:Rats, Long-Evans
D004317:Doxorubicin