Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

Clement, Sandhya; Campbell, Jared M.; Deng, Wei; Guller, Anna; Nisar, Saadia; Liu, Guozhen; Wilson, Brian C.; Goldys, Ewa M.

doi:10.1002/advs.202003584

Cited by 61 publications

(56 citation statements)

References 374 publications

(445 reference statements)

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“…Similar findings for other PSs (e.g., protoporpyrin IX) have been reported by other groups [20][21][22]. As we have recently reviewed in detail [23], the mechanisms of ROS generation in RDT are not fully understood but include direct PS activation by secondary electrons, the use of scintillation nanocrystals to convert X-ray energy into light, and PS activation by the Cerenkov light generated by high-energy secondary electrons produced in tissue by MeV X-rays.…”

Section: Introductionsupporting

confidence: 84%

Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles

Clement

Anwer

Pires

et al. 2021

IJMS

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Radiodynamic therapy (RDT) is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of high-energy X-rays. This enables greater tissue penetration to allow non-invasive treatment of large, deep-seated tumors. We report here the design and testing of a drug delivery system for RDT that is intended to enhance intra- or peri-nuclear localization of the photosensitizer, leading to DNA damage and resulting clonogenic cell kill. This comprises a photosensitizer (Verteporfin, VP) incorporated into poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) that are surface-functionalized with a cell-penetrating HIV trans-activator of transcription (TAT) peptide. In addition to a series of physical and photophysical characterization studies, cytotoxicity tests in pancreatic (PANC-1) cancer cells in vitro under 4 Gy X-ray exposure from a clinical 6 MV linear accelerator (LINAC) showed that TAT targeting of the nanoparticles markedly enhances the effectiveness of RDT treatment, particularly when assessed by a clonogenic, i.e., DNA damage-mediated, cell kill.

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Section: Introductionsupporting

confidence: 84%

Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles

Clement

Anwer

Pires

et al. 2021

IJMS

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“…This is because the hyperthermia in tumor caused by strong and efficient PTT can increase vascular permeability, which is conducive to enhancing PD-L1 antibody infiltration efficiency. [23] Moreover, the accumulation of CD4 + and CD8 + T lymphocytes in tumor is increased, which is most apparent in NPs + laser + anti-PD-L1 group (Figure 6K). These results further reveal that the combination of DDTB-DP NPsmediated PTT/PDT and PD-L1 antibody effectively induces…”

Section: Resultsmentioning

confidence: 93%

Improving Image‐Guided Surgical and Immunological Tumor Treatment Efficacy by Photothermal and Photodynamic Therapies Based on a Multifunctional NIR AIEgen

et al. 2021

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Multimodal therapy is attracting increasing attention to improve tumor treatment efficacy, but generally requires various complicated ingredients combined within one theranostic system to achieve multiple functions. Herein, a multifunctional theranostic nanoplatform based on a single aggregation‐induced‐emission luminogen (AIEgen), DDTB, is designed to integrate near‐infrared (NIR) fluorescence, photothermal, photodynamic, and immunological effects. Intravenously injected AIEgen‐based nanoparticles can efficiently accumulate in tumors with NIR fluorescence to provide preoperative diagnosis. Most of the tumors are excised under intraoperative fluorescence navigation, whereafter, some microscopic residual tumors are completely ablated by photodynamic and photothermal therapies for maximally killing the tumor cells and tissues. Up to 90% of the survival rate can be achieved by this synergistic image‐guided surgery and photodynamic and photothermal therapies. Importantly, the nanoparticles‐mediated photothermal/photodynamic therapy plus programmed death‐ligand 1 antibody significantly induce tumor elimination by enhancing the effect of immunotherapy. This theranostic strategy on the basis of a single AIEgen significantly improves the survival of cancer mice with maximized therapeutic outcomes, and holds great promise for clinical cancer treatment.

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“…In the following sections, we outline several resistance traits of pancreatic tumours that predispose patients to therapy failure and discuss how these can be effectively surmounted through use of nanotechnology. While radioresistance is a common feature of PaCa and there are nano-based strategies to tackle this issue, it is beyond the scope of this current article and discussed in more detail elsewhere [ 89 , 90 , 91 ].…”

Section: Addressing Therapy Resistance In Paca Using Nanoparticle-based Platformsmentioning

confidence: 99%

Nanomedicine in Pancreatic Cancer: Current Status and Future Opportunities for Overcoming Therapy Resistance

Greene

Johnston

Scott

2021

Cancers

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The development of drug resistance remains one of the greatest clinical oncology challenges that can radically dampen the prospect of achieving complete and durable tumour control. Efforts to mitigate drug resistance are therefore of utmost importance, and nanotechnology is rapidly emerging for its potential to overcome such issues. Studies have showcased the ability of nanomedicines to bypass drug efflux pumps, counteract immune suppression, serve as radioenhancers, correct metabolic disturbances and elicit numerous other effects that collectively alleviate various mechanisms of tumour resistance. Much of this progress can be attributed to the remarkable benefits that nanoparticles offer as drug delivery vehicles, such as improvements in pharmacokinetics, protection against degradation and spatiotemporally controlled release kinetics. These attributes provide scope for precision targeting of drugs to tumours that can enhance sensitivity to treatment and have formed the basis for the successful clinical translation of multiple nanoformulations to date. In this review, we focus on the longstanding reputation of pancreatic cancer as one of the most difficult-to-treat malignancies where resistance plays a dominant role in therapy failure. We outline the mechanisms that contribute to the treatment-refractory nature of these tumours, and how they may be effectively addressed by harnessing the unique capabilities of nanomedicines. Moreover, we include a brief perspective on the likely future direction of nanotechnology in pancreatic cancer, discussing how efforts to develop multidrug formulations will guide the field further towards a therapeutic solution for these highly intractable tumours.

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Mechanisms for Tuning Engineered Nanomaterials to Enhance Radiation Therapy of Cancer

Cited by 61 publications

References 374 publications

Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles

Radiodynamic Therapy Using TAT Peptide-Targeted Verteporfin-Encapsulated PLGA Nanoparticles

Improving Image‐Guided Surgical and Immunological Tumor Treatment Efficacy by Photothermal and Photodynamic Therapies Based on a Multifunctional NIR AIEgen

Nanomedicine in Pancreatic Cancer: Current Status and Future Opportunities for Overcoming Therapy Resistance

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