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Protease Responsive Essential Amino-Acid Based Nanocarriers for Near-Infrared Imaging.

ABSTRACT: Delivery of the theranostic agents with effective concentration to the desired sites inside the body is a major challenge in disease management. Nanotechnology has gained attention for the delivery of theranostic agents to the targeted location. The use of essential amino-acid based homopolymers for the synthesis of biocompatible and biodegradable nanoparticles (NPs) could serve as a nanocarrier for delivery applications. In this study, poly-l-lysine (PLL) and salts were used to fabricate the NPs for the delivery of exogenous contrast agents. Here, indocyanine green (ICG) was encapsulated within these NPs, and a simple two-step green chemistry-based self-assembly process was used for the fabrication. The morphological and biochemical characterizations confirm the formation of ICG encapsulating spherical PLL NPs with an average diameter of ~225?nm. Further, a detailed study has been carried out to understand the role of constituents in the assembly mechanism of PLL NPs. Our results show a controlled release of the ICG from PLL NPs in the presence of the proteolytic enzyme. In-vitro cellular studies suggest that the PLL NPs were readily taken up by the cells showing their superior delivery efficiency of ICG in comparison to the free-form of the ICG.

SUBMITTER: Kumari A

PROVIDER: S-EPMC6937316 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Project description:IntroductionDespite significant progress in the field of oncology, cancer remains one of the leading causes of death. Chemotherapy is one of the most common treatment options for cancer patients but is well known to result in off-target toxicity. Theranostic nanomedicines that integrate diagnostic and therapeutic functions within an all-in-one platform can increase tumor selectivity for more effective chemotherapy and aid in diagnosis and monitoring of therapeutic responses.Material and methodsIn this work, theranostic nanoparticles were synthesized with commonly used biocompatible and biodegradable polymers and used as cancer contrast and therapeutic agents for optical imaging and treatment of breast cancer. These core-shell nanoparticles were prepared by nanoprecipitation of blends of the biodegradable and biocompatible amphiphilic copolymers poly(lactic-co-glycolic acid)-b-poly-l-lysine and poly(lactic acid)-b-poly(ethylene glycol). Poly-l-lysine in the first copolymer was covalently decorated with near-infrared fluorescent Alexa Fluor 750 molecules.ResultsThe spherical nanoparticles had an average size of 60-80 nm. The chemotherapeutic drug doxorubicin was encapsulated in the core of nanoparticles at a loading of 3% (w:w) and controllably released over a period of 30 days. A 33-fold increase in near-infrared fluorescence, mediated by protease-mediated cleavage of the Alexa Fluor 750-labeled poly-l-lysine on the surface of the nanoparticles, was observed upon interaction with the model protease trypsin. The cytocompatibility of drug-free nanoparticles and growth inhibition of drug-loaded nanoparticles on MDA-MB-231 breast cancer cells were investigated with a luminescence cell-viability assay. Drug-free nanoparticles were found to cause minimal toxicity, even at high concentrations (0.2-2,000 µg/mL), while doxorubicin-loaded nanoparticles significantly reduced cell viability at drug concentrations >10 µM. Finally, the interaction of the nanoparticles with breast cancer cells was studied utilizing fluorescence microscopy, demonstrating the potential of the nanoparticles to act as near-infrared fluorescence optical imaging agents and drug-delivery carriers.ConclusionDoxorubicin-loaded, enzymatically activatable nanoparticles of less than 100 nm were prepared successfully by nanoprecipitation of copolymer blends. These nanoparticles were found to be suitable as controlled drug delivery systems and contrast agents for imaging of cancer cells.

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Protease Responsive Essential Amino-Acid Based Nanocarriers for Near-Infrared Imaging.

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