PEG-PLGA nanospheres loaded with nanoscintillators and photosensitizers for radiation-activated photodynamic therapy

Dinakaran, Deepak; Sengupta, Jayeeta; Pink, Desmond; Raturi, Arun; Chen, Hua; Usmani, Nawaid; Kumar, Piyush; Lewis, John D.; Narain, Ravin; Moore, Ronald B.

doi:10.1016/j.actbio.2020.09.029

Cited by 27 publications

(24 citation statements)

References 48 publications

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“…Both formulations displayed potent phototoxic effects against A549 cells. 42,43 Dinakaran et al 47 developed a PEG-PLGA-based delivery system encapsulating Protoporphyrin IX for targeting deep-seated tumors, upon laser activation, this formulation exhibited effective cytotoxicity against PC3 cells (human prostate cancer cell lines). Additionally, Verger et al 48 engineered PLGA nanoparticles loaded with a molybdenum cluster compound to enhance the efficacy of photodynamic therapy for ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

The evaluation of four nano-formulations loaded-Elsinochrome A on characteristics and in vitro cytotoxicity effect

Yao,

Wu,

Pan

et al. 2023

J Biomater Appl

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Elsinochrome A (EA) is a naturally occurring photosensitizer with potential applications in photodynamic therapy (PDT) for various malignancies. Despite its promising therapeutic properties, the poor solubility of EA hampers its effective utilization in clinical settings. To circumvent this limitation, we engineered four distinct nano-formulations: PLGA/EA nanoparticles (NPs), CMC-PLGA/EA NPs, mPEG-PCL/EA nanomicelles (NMs), and LHP-CHOL/EA nanoliposomes (NLs), all designed to enhance the solubility of EA. A comparative evaluation of these formulations, based on metrics such as particle size, Zeta potential, drug loading efficiency, and encapsulation efficiency, identified PLGA/EA NPs and mPEG-PCL/EA NMs as the most efficacious candidates. Subsequent in vitro investigations into the drug release kinetics under varying pH conditions and the impact on cell viability and apoptosis in A549 and MCF-7 cell lines were conducted. Remarkably, the maximum drug release for PLGA/EA NPs and mPEG-PCL/EA NMs was recorded at 62.5% and 70.8% in an acidic environment (pH 5.7), respectively. Upon exposure to 460 nm light, PLGA/EA NPs induced a significant reduction in A549 cell viability to 13.8% and an apoptosis rate of 93.8%, whereas mPEG-PCL/EA NMs elicited a decrease in MCF-7 cell viability to 12.8% and an apoptosis rate of 73.0%.

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Section: Discussionmentioning

confidence: 99%

The evaluation of four nano-formulations loaded-Elsinochrome A on characteristics and in vitro cytotoxicity effect

Yao,

Wu,

Pan

et al. 2023

J Biomater Appl

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“…In the current investigation, we intratumorally injected CsI(Na) nanoparticles in therapy studies, which is common among RDT studies [ 22 , 26 , 27 , 59 ]. The injection route is viable for treating cancer types such as breast, prostate, and skin cancers [ 22 , 31 , 60 ]. It is possible to systemically administer CsI(Na) nanoparticles, whereby they accumulate in tumors through passive or active targeting.…”

Section: Discussionmentioning

confidence: 99%

Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid

et al. 2022

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Background Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator–photosensitizer nanoconjugates are often used, posing barriers for large-scale manufacturing and regulatory approval. Methods Herein, we report a streamlined RDT strategy based on CsI(Na)@MgO nanoparticles and 5-aminolevulinic acid (5-ALA). 5-ALA is a clinically approved photosensitizer, converted to protoporphyrin IX (PpIX) in cancer cells’ mitochondria. CsI(Na)@MgO nanoparticles produce strong ~ 410 nm X-ray luminescence, which matches the Soret band of PpIX. We hypothesize that the CsI(Na)@MgO-and-5-ALA combination can mediate RDT wherein mitochondria-targeted PDT synergizes with DNA-targeted irradiation for efficient cancer cell killing. Because scintillator nanoparticles and photosensitizer are administered separately, the approach forgoes issues such as self-quenching or uncontrolled release of photosensitizers. Results When tested in vitro with 4T1 cells, the CsI(Na)@MgO and 5-ALA combination elevated radiation-induced reactive oxygen species (ROS), enhancing damages to mitochondria, DNA, and lipids, eventually reducing cell proliferation and clonogenicity. When tested in vivo in 4T1 models, RDT with the CsI(Na)@MgO and 5-ALA combination significantly improved tumor suppression and animal survival relative to radiation therapy (RT) alone. After treatment, the scintillator nanoparticles, made of low-toxic alkali and halide elements, were efficiently excreted, causing no detectable harm to the hosts. Conclusions Our studies show that separately administering CsI(Na)@MgO nanoparticles and 5-ALA represents a safe and streamlined RDT approach with potential in clinical translation. Graphical Abstract

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“…Another factor affecting the therapeutic effect is the distance between the PS and the scintillator. One approach is to physically package PS in a coating bound to the scintillator by electrostatic or hydrophobic means or to load both the scintillator and PS into NPs [186,187]; for example, the combination of protoporphyrin IX (PpIX) and scintillator LaF 3 :Ce 3+ coloaded in PEG-PLGA was shown to exhibit highly efficient loading and high stability under physiological conditions [188]. Physical combination has a certain risk of missing the target, whereas chemical bonding based on covalent bonds or conjugation is complex but more stable.…”

Section: Radiotherapymentioning

confidence: 99%

Progress in Nanocarriers Codelivery System to Enhance the Anticancer Effect of Photodynamic Therapy

2021

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Photodynamic therapy (PDT) is a promising anticancer noninvasive method and has great potential for clinical applications. Unfortunately, PDT still has many limitations, such as metastatic tumor at unknown sites, inadequate light delivery and a lack of sufficient oxygen. Recent studies have demonstrated that photodynamic therapy in combination with other therapies can enhance anticancer effects. The development of new nanomaterials provides a platform for the codelivery of two or more therapeutic drugs, which is a promising cancer treatment method. The use of multifunctional nanocarriers for the codelivery of two or more drugs can improve physical and chemical properties, increase tumor site aggregation, and enhance the antitumor effect through synergistic actions, which is worthy of further study. This review focuses on the latest research progress on the synergistic enhancement of PDT by simultaneous multidrug administration using codelivery nanocarriers. We introduce the design of codelivery nanocarriers and discuss the mechanism of PDT combined with other antitumor methods. The combination of PDT and chemotherapy, gene therapy, immunotherapy, photothermal therapy, hyperthermia, radiotherapy, sonodynamic therapy and even multidrug therapy are discussed to provide a comprehensive understanding.

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PEG-PLGA nanospheres loaded with nanoscintillators and photosensitizers for radiation-activated photodynamic therapy

Cited by 27 publications

References 48 publications

The evaluation of four nano-formulations loaded-Elsinochrome A on characteristics and in vitro cytotoxicity effect

The evaluation of four nano-formulations loaded-Elsinochrome A on characteristics and in vitro cytotoxicity effect

Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid

Progress in Nanocarriers Codelivery System to Enhance the Anticancer Effect of Photodynamic Therapy

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