Abstract 4160: V7 targeted liposomes detect pancreatic adenocarcinoma via multispectral optoacoustic tomography
Authors: Agarwal Happy , Chuong Phillip , Grizzle William E. , Edil Barish H. , Jain Ajay , McNally Lacey R. 
Published: March 2024

Purpose: Pancreatic ductal adenocarcinoma (PDA) remains one of the most aggressive malignancies with a 5-year survival rate of 9-10%. Insufficient early detection coupled with limitations in operating surgery renders PDA as one of the most challenging tumors to treat. Accurate localization of tumor margins can tremendously improve surgical treatment outcomes in patients. Recently, nanotechnology has emerged as a promising platform for theranostic applications in the field of drug discovery, although the clinical success is limited by their tumor-specific uptake. Hypoxia due to aberrant vascularization is a hallmark of PDA and can be exploited for active targeting. pH-low insertion peptide variant 7 (V7) is used as hypoxia and acidosis-dependent biomarker for selective targeting of pancreatic cancer tissue. This work is focused on using IR 780 contrast agent loaded, V7 peptide conjugated liposomes for the active targeting of PDA towards enhanced surgical outcomes.

Methods: Liposomes encapsulating IR780 dye were prepared using thin film hydration technique. V7 peptide was conjugated to liposomes using an SMCC linker and liposomes were characterized for their size, polydispersity and surface potential. In-vitro uptake of IR780-V7-liposome by S2VP10 at pH 7.4, 6.8, and 6.6 was evaluated through NIR fluorescence imaging using an Odyssey Infrared System. Athymic mice were orthotopically implanted with S2VP10 cells. After tumors were 3 mm, V7-liposomes and untargeted liposomes (0.01 OD) were intravenously injected and biodistribution and tumor specific uptake was accessed using multispectral optoacoustic imaging (MSOT).

Results: Dynamic light scattering (DLS) revealed the size of liposomes to be 109 nm with a polydispersity index of 0.198 and zeta potential of +35.8 mV. Surface conjugation of V7 peptide was confirmed using the zeta potential measurement. NIR fluorescence imaging in S2VP10 cells established enhanced tumor specific uptake of V7 conjugated liposomes than passively targeted liposomes (p&lt;0.05). Biodistribution of V7-liposomes demonstrated tumor specific accumulation (PDAC tumor 23.7 a.u, liver 3.6 a.u., and kidney 1.1 a.u.) while untargeted liposomes had the greatest uptake in liver (PDAC tumor 2.1 a.u., liver 6.3 a.u., and kidney 0.7 a.u.) p&lt;0.05.

Conclusion: pH-specific actively targeted liposomes can be used to specifically target PDA with minimal off-target binding effects. V7-IR780-liposome formulation can be used to efficiently deliver contrast agent for imaging tumor margins and to expand the potential of MSOT towards clinical applications.

Citation Format: Happy Agarwal, Phillip Chuong, William E. Grizzle, Barish H. Edil, Ajay Jain, Lacey R. McNally. V7 targeted liposomes detect pancreatic adenocarcinoma via multispectral optoacoustic tomography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4160.