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Eutectic Gallium-Indium Nanoparticles for Photodynamic Therapy of Pancreatic Cancer.

ABSTRACT: Developing a cancer theranostic nanoplatform with diagnosis and treatment capabilities to effectively treat tumors and reduce side effects is of great significance. Herein, we present a drug delivery strategy for photosensitizers based on a new liquid metal nanoplatform that leverages the tumor microenvironment to achieve photodynamic therapeutic effects in pancreatic cancer. Eutectic gallium indium (EGaIn) nanoparticles were successfully conjugated with a water-soluble cancer targeting ligand, hyaluronic acid, and a photosensitizer, benzoporphyrin derivative, creating EGaIn nanoparticles (EGaPs) via a simple green sonication method. The prepared sphere-shaped EGaPs, with a core-shell structure, presented high biocompatibility and stability. EGaPs had greater cellular uptake, manifested targeting competence, and generated significantly higher intracellular ROS. Further, near-infrared light activation of EGaPs demonstrated their potential to effectively eliminate cancer cells due to their single oxygen generation capability. Finally, from in vivo studies, EGaPs caused tumor regression and resulted in 2.3-fold higher necrosis than the control, therefore making a good vehicle for photodynamic therapy. The overall results highlight that EGaPs provide a new way to assemble liquid metal nanomaterials with different ligands for enhanced cancer therapy.

SUBMITTER: Hafiz SS

PROVIDER: S-EPMC9150699 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Eutectic Gallium-Indium Nanoparticles for Photodynamic Therapy of Pancreatic Cancer.

Hafiz Sabrina S SS Xavierselvan Marvin M Gokalp Sumeyra S Labadini Daniela D Barros Sebastian S Duong Jeanne J Foster Michelle M Mallidi Srivalleesha S

ACS applied nano materials 20220515 5

Developing a cancer theranostic nanoplatform with diagnosis and treatment capabilities to effectively treat tumors and reduce side effects is of great significance. Herein, we present a drug delivery strategy for photosensitizers based on a new liquid metal nanoplatform that leverages the tumor microenvironment to achieve photodynamic therapeutic effects in pancreatic cancer. Eutectic gallium indium (EGaIn) nanoparticles were successfully conjugated with a water-soluble cancer targeting ligand, ...[more]

PMID: 35655927

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Project description:With less than 10% of 5-year survival rate, pancreatic ductal adenocarcinoma (PDAC) is known to be one of the most lethal types of cancer. Current literature supports that gemcitabine is the first-line treatment of PDAC. However, poor cellular penetration of gemcitabine along with the acquired and intrinsic chemoresistance of tumor against it often reduced its efficacy and hence necessitates the administration of high gemcitabine dose during chemotherapy. Photodynamic therapy (PDT), a more selective and minimally invasive treatment, may be used synergistically with gemcitabine to reduce the doses utilized and dose-related side effects. This study reports the synergistic use of Re(I) bisquinolinyl complex, a transition metal complex photosensitizer with gemcitabine against PDAC. Re(I) bisquinolinyl complex was found to act synergistically with gemcitabine against PDAC in vitro at various ratios. With the aim to enhance cellular uptake and therapeutic efficiency, the Re(I) bisquinolinyl complex and gemcitabine were encapsulated into liquid crystalline nanoparticles (LCNPs) system. The formulations were found to produce homogeneous drug-loaded LCNPs (average size: 159-173 nm, zeta potential +1.06 to -10 mV). Around 70% of gemcitabine and 90% of the Re(I) bisquinolinyl complex were found to be entrapped efficiently in the formulated LCNPs. The release rate of gemcitabine or/and the Re(I) bisquinolinyl complex loaded into LCNPs was evaluated in vitro, and the hydrophilic gemcitabine was released at a faster rate than the lipophilic Re(I) complex. LCNPs loaded with gemcitabine and Re(I) bisquinolinyl complex in a 1:1 ratio illustrated the best anti-cancer activity among the LCNP formulations (IC50 of BxPC3: 0.15 μM; IC50 of SW 1990: 0.76 μM) through apoptosis. The current findings suggest the potential use of transition metal-based photosensitizer as an adjunctive agent for gemcitabine-based chemotherapy against PDAC and the importance of nano-formulation in such application.

Dataset Information

Eutectic Gallium-Indium Nanoparticles for Photodynamic Therapy of Pancreatic Cancer.

Publications

Eutectic Gallium-Indium Nanoparticles for Photodynamic Therapy of Pancreatic Cancer.

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