Active Targeting Significantly Outperforms Nanoparticle Size in Facilitating Tumor-Specific Uptake in Orthotopic Pancreatic Cancer

• Published in: ACS applied materials & interfaces Vol. 13; no. 42; pp. 49614 - 49630
• Main Authors: MacCuaig, William M, Fouts, Benjamin L, McNally, Molly W, Grizzle, William E, Chuong, Phillip, Samykutty, Abhilash, Mukherjee, Priyabrata, Li, Min, Jasinski, Jacek B, Behkam, Bahareh, McNally, Lacey R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27.10.2021
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and Medical Applications of Materials and Interfaces; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Drug Screening Assays, Antitumor; Female; Humans; Materials Testing; Mice; Mice, Nude; Nanoparticles - chemistry; Nanoparticles - metabolism; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Particle Size; Peptides - chemistry; Peptides - pharmacology; actively targeted nanoparticles; nanoparticle size; mesoporous silica nanoparticles; pancreatic cancer; tumor specificity
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c09379

Nanoparticles are widely studied as theranostic vehicles for cancer; however, clinical translation has been limited due to poor tumor specificity. Features that maximize tumor uptake remain controversial, particularly when using clinically relevant models. We report a systematic study that assesses two major features for the impact on tumor specificity, i.e., active vs passive targeting and nanoparticle size, to evaluate relative influences in vivo. Active targeting via the V7 peptide is superior to passive targeting for uptake by pancreatic tumors, irrespective of nanoparticle size, observed through in vivo imaging. Size has a secondary effect on uptake for actively targeted nanoparticles in which 26 nm nanoparticles outperform larger 45 and 73 nm nanoparticles. Nanoparticle size had no significant effect on uptake for passively targeted nanoparticles. Results highlight the superiority of active targeting over nanoparticle size for tumor uptake. These findings suggest a framework for optimizing similar nonaggregate nanoparticles for theranostic treatment of recalcitrant cancers.