Functional Single-Chain Polymer Nanoparticles: Targeting and Imaging Pancreatic Tumors in Vivo

Abstract

The development of tools for the early diagnosis of pancreatic adenocarcinoma is an urgent need in order to increase treatment success rate and reduce patient mortality. Here, we present a modular nanosystem platform integrating soft nanoparticles with a targeting peptide and an active imaging agent for diagnostics. Biocompatible single-chain polymer nanoparticles (SCPNs) based on poly(methacrylic acid) were prepared and functionalized with the somatostatin analogue PTR86 as the targeting moiety, since somatostatin receptors are overexpressed in pancreatic cancer. The gamma emitter Ga was incorporated by chelation and allowed in vivo investigation of the pharmacokinetic properties of the nanoparticles using single photon emission computerized tomography (SPECT). The resulting engineered nanosystem was tested in a xenograph mouse model of human pancreatic adenocarcinoma. Imaging results demonstrate that accumulation of targeted SCPNs in the tumor is higher than that observed for nontargeted nanoparticles due to improved retention in this tissue.

Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media

“…19 In pursuit of novel types of biocompatible polymeric nanoparticles based on readily available and easily functionalized materials, we here present a novel and straightforward synthetic methodology to obtain small (approximately 13 nm) dextran (DXT)-based SCPNs through the intramolecular crosslinking (compaction) of single polysaccharide chains by means of a homobifunctional crosslinker in aqueous media and mild conditions. Dextran-40 (40 KDa, DXT) and 3,6-dioxa-1,8-octane-dithiol (DODT), both commercially available and relatively cheap, were selected as the polysaccharide and the cross-linker, respectively.…”

Application of Polymersomes Engineered to Target P32 Protein for Detection of Small Breast Tumors in Mice

“…The current study documents high tumor accumulation of LinTT1-polymersomes (>20% ID/cc) that translates into an ability to detect very small malignant lesions, barely visible by CT. This sets our system apart from other molecular and nanoparticle PET contrast agents with reported tumor accumulations between 5-10% ID/g [42][43] [44]. Remarkable tumor selectivity and tumor binding capacity observed for the LinTT1-polymersomes is likely to be due to a combination of the tumor homing properties of LinTT1 peptide with the favorable properties of the PEG-PCL polymersome nanoplatform.…”

“…The current study documents high tumor accumulation of LinTT1polymersomes (>20% ID/cc) that translates into ability to detect very small malignant lesions, barely visible by CT. This sets our system apart from other molecular and nanoparticle PET contrast agents with reported tumor accumulation range between 5-10% ID/g [31][32] [33].…”

Nucleic acids presenting polymer nanomaterials as vaccine adjuvants

“…Water-soluble SCNPs have been explored in biomedical applications including drug-delivery and as in vivo imaging reagents, while their use as immune-modulating compounds remains limited to one study. 128,129 Nativi and co-workers incorporated the a-Tn antigen mimetic moiety to dextran SCNPs to trigger immune responses similar to immune proteins on human peripheral blood mononuclear cells (PBMCs). 130 Since the native antigen has limitations in terms of stability and antibody response, presentation on a SCNP was hypothesized to enhance the immune active potential.…”

“…For single chain polymer nanoparticles, to date only initial toxicity evaluations have been performed revealing minimal toxicities that are predominantly related to the presence of external contaminants, such as metal ions or primary amines. 129 For a future translation of SCNPs as therapeutic biomaterials, detailed studies are required to gain a general understanding of SCNP-related toxicity and biodistribution.…”