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Synthesis and characterization of a tumor-seeking LyP-1 peptide integrated lipid–polymer composite nanoparticle

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Abstract

Biocompatible polymeric and lipid nanoparticles are under extensive investigation as anticancer nanomedicines due to the ease of chemical modification in both polymer and lipid in order to target the respective disease environment. However, microenvironment and molecular heterogeneity in tumors pose a great challenge to delivering anticancer drugs or imaging agents precisely to the target, further limiting their applications. As a result, existing nanomedicine formulations rely on a passive-drug targeting mechanism taking advantage of leaky tumor vasculature. However, one strategy is not fit for all due to the molecular dissimilarities between cancers. Therefore, more research on tumor-specific receptors is needed to maximize drug delivery, while minimizing drug-related adverse effects. In addition, a high degree of the immunocompatibility and aqueous stability of the delivery device is essential to maximize delivery efficiency. Herein, we are addressing the aforementioned requirements in cancer management by engineering a receptor-specific anticancer nanomedicine as a composite of polymer and lipids. We are presenting a tumor seeking cyclic LyP-1 peptide integrated core–shell polymer–lipid composite nanoparticle (NP) that targets the overexpressed p32 receptor in cancer cells. The designed nanoconstruct is composed of poly(lactide-co-glycolic acid) as a skeleton and a cargo reservoir, a phospholipid with polyethylene glycol as a stabilizer, and LyP-1 as a targeting motif. We studied cellular interaction and targeting ability by accessing the full spectrum of biodistribution using NPs labeled with near-infrared dye as an imaging tracer in vivo. The NPs are spherical and monodispersed with an average size of 68 ± 6 nm and negative zeta potential. These particles are highly stable in physiological conditions over the period with a lower polydispersity index (PDI = 0.15). Furthermore, the nanoparticles showed excellent biocompatibility in vitro, with significantly higher uptake by mouse osteosarcoma compared to non-cancerous fibroblasts. Likewise, LyP-1 NP showed nearly three-fold enhancement in tumor accumulation in vivo compared to its non-targeted counterparts in the K7M2 tumor. Considering the overexpression of p32 in many cancers, the proposed nanoconstruct could hold promises in the therapeutic planning of a wide range of tumors.

Graphical abstract: Synthesis and characterization of a tumor-seeking LyP-1 peptide integrated lipid–polymer composite nanoparticle

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Supplementary files

Article information


Submitted
14 Apr 2020
Accepted
08 May 2020
First published
11 May 2020

This article is Open Access

Mater. Adv., 2020, Advance Article
Article type
Paper

Synthesis and characterization of a tumor-seeking LyP-1 peptide integrated lipid–polymer composite nanoparticle

R. Marasini, T. D. T. Nguyen, S. Rayamajhi and S. Aryal, Mater. Adv., 2020, Advance Article , DOI: 10.1039/D0MA00203H

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