Soft Discoidal Polymeric Nanoconstructs Resist Macrophage Uptake and Enhance Vascular Targeting in Tumors.
Most nanoparticles for biomedical applications originate from the self-assembling of individual constituents through molecular interactions and possess limited geometry control and stability. Here, 1000 × 400 nm discoidal polymeric nanoconstructs (DPNs) are demonstrated by mixing hydrophobic and hydrophilic polymers with lipid chains and curing the resulting paste directly within silicon templates. By changing the paste composition, soft- and rigid-DPNs (s- and r-DPNs) are synthesized exhibiting the same geometry, a moderately negative surface electrostatic charge (-14 mV), and different mechanical stiffness (∼1.3 and 15 kPa, respectively). Upon injection in mice bearing nonorthotopic brain or skin cancers, s-DPNs exhibit ∼24 h circulation half-life and accumulate up to ∼20% of the injected dose per gram tumor, detecting malignant masses as small as ∼0.1% the animal weight via PET imaging. This unprecedented behavior is ascribed to the unique combination of geometry, surface properties, and mechanical stiffness which minimizes s-DPN sequestration by the mononuclear phagocyte system. Our results could boost the interest in using less conventional delivery systems for cancer theranosis.
Department of Translational Imaging and Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.|Department of Biomedical Engineering, Yonsei University , 1 Yonseidae-gil, Wonju, Gangwon-do 220-710, South Korea.
Jaehong
J
Key
Department of Translational Imaging and Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.|Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia (IIT) , via Morego 30, Genova I16163, Italy.
Anna Lisa
AL
Palange
Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia (IIT) , via Morego 30, Genova I16163, Italy.
Francesco
F
Gentile
Department of Translational Imaging and Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.|Department of Chemistry, Nanotechnology Innovation Center of Kansas State, Kansas State University , Manhattan, Kansas 66506, United States.
Santosh
S
Aryal
Department of Translational Imaging and Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.
Cinzia
C
Stigliano
Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia (IIT) , via Morego 30, Genova I16163, Italy.
Daniele
D
Di Mascolo
Department of Translational Imaging and Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.
Enrica
E
De Rosa
Department of Translational Imaging and Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.
Minjung
M
Cho
Department of Translational Imaging and Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.
Yeonju
Y
Lee
Department of Translational Imaging and Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.
Jaykrishna
J
Singh
Department of Translational Imaging and Department of Nanomedicine, Houston Methodist Research Institute , Houston, Texas 77030, United States.|Department of Experimental and Clinical Medicine, University of Magna Graecia , Catanzaro 88100, Italy.|Laboratory of Nanotechnology for Precision Medicine, Fondazione Istituto Italiano di Tecnologia (IIT) , via Morego 30, Genova I16163, Italy.
Paolo
P
Decuzzi
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D005290:Ferric Compounds; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011108:Polymers / Q000737:chemistry*
D000970:Antineoplastic Agents; D005290:Ferric Compounds; D011108:Polymers; C000499:ferric oxide
iron oxide nanocubes; macrophage uptake; nanoparticle shape; nanoparticle stiffness; tumor imaging