Predictors and Limitations of the Penetration Depth of Photodynamic Effects in the Rodent Brain

Inglut, Collin T.; Gaitan, Brandon; Najafali, Daniel; Lopez, Irati Abad; Connolly, Nina P.; Orsila, S.; Perttilä, Robert; Woodworth, Graeme F.; Chen, Yu; Huang, Huang‐Chiao

doi:10.1111/php.13155

Cited by 25 publications

(21 citation statements)

References 81 publications

(118 reference statements)

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“…Nanoliposome (Nal) and nanoliposomal irinotecan (Nal–IRI) were prepared following freeze–thaw extrusion method [21, 22, 48, 49]. Briefly, cholesterol, dipalmitoylphosphatidylcholine (DPPC), distearoyl-phosphatidylethanolamine-methoxy polyethylene glycol (DSPE-mPEG2000), distearoyl-glycerophosphoethanolamine-N-dibenzocyclooctyl polyethylene glycol (DSPE-mPEG2000-DBCO), and dioleoylglycerophosphoglycerol (DOPG; Avanti) were mixed at a molar ratio of 2.8:6:0.4:0.2:0.6.…”

Section: Methodsmentioning

confidence: 99%

Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting

et al. 2020

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BackgroundPhotoimmunotherapy involves targeted delivery of photosensitizers via an antibody conjugate (i.e., photoimmunoconjugate, PIC) followed by light activation for selective tumor killing. The trade-off between PIC selectivity and PIC uptake is a major drawback limiting the efficacy of photoimmunotherapy. Despite ample evidence showing that photoimmunotherapy is most effective when combined with chemotherapy, the design of nanocarriers to co-deliver PICs and chemotherapy drugs remains an unmet need. To overcome these challenges, we developed a novel photoimmunoconjugate-nanoliposome (PIC-Nal) comprising of three clinically used agents: anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody cetuximab (Cet), benzoporphyrin derivative (BPD) photosensitizer, and irinotecan (IRI) chemotherapy.ResultsThe BPD photosensitizers were first tethered to Cet at a molar ratio of 6:1 using carbodiimide chemistry to form PICs. Conjugation of PICs onto nanoliposome irinotecan (Nal–IRI) was facilitated by copper-free click chemistry, which resulted in monodispersed PIC–Nal–IRI with an average size of 158.8 ± 15.6 nm. PIC–Nal–IRI is highly selective against EGFR-overexpressing epithelial ovarian cancer cells with 2- to 6-fold less accumulation in low EGFR expressing cells. Successful coupling of PIC onto Nal–IRI enhanced PIC uptake and photoimmunotherapy efficacy by up to 30% in OVCAR-5 cells. Furthermore, PIC–Nal–IRI synergistically reduced cancer viability via a unique three-way mechanism (i.e., EGFR downregulation, mitochondrial depolarization, and DNA damage).ConclusionIt is increasingly evident that the most effective therapies for cancer will involve combination treatments that target multiple non-overlapping pathways while minimizing side effects. Nanotechnology combined with photochemistry provides a unique opportunity to simultaneously deliver and activate multiple drugs that target all major regions of a cancer cell—plasma membrane, cytoplasm, and nucleus. PIC–Nal–IRI offers a promising strategy to overcome the selectivity-uptake trade-off, improve photoimmunotherapy efficacy, and enable multi-tier cancer targeting. Controllable drug compartmentalization, easy surface modification, and high clinical relevance collectively make PIC–Nal–IRI extremely valuable and merits further investigations in living animals.

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Section: Methodsmentioning

confidence: 99%

Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting

et al. 2020

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“…The deeper light penetration is also pursued to a greater or lower extent following diverse approaches—namely, two-photon excitation [ 85 ], repeated PDT procedures [ 86 , 87 ], enhanced PS [ 88 ], a combination of PSs [ 89 ], X-rays, and internal bioluminescence [ 90 ]. The use of optical clearing agents is promising not only for deep-light delivery but also for characterisation and deep-monitoring [ 91 , 92 ].…”

Section: Light Technology For Pdtmentioning

confidence: 99%

Light Technology for Efficient and Effective Photodynamic Therapy: A Critical Review

Algorri

Ochoa

Roldán-Varona

et al. 2021

Cancers

103

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Photodynamic therapy (PDT) is a cancer treatment with strong potential over well-established standard therapies in certain cases. Non-ionising radiation, localisation, possible repeated treatments, and stimulation of immunological response are some of the main beneficial features of PDT. Despite the great potential, its application remains challenging. Limited light penetration depth, non-ideal photosensitisers, complex dosimetry, and complicated implementations in the clinic are some limiting factors hindering the extended use of PDT. To surpass actual technological paradigms, radically new sources, light-based devices, advanced photosensitisers, measurement devices, and innovative application strategies are under extensive investigation. The main aim of this review is to highlight the advantages/pitfalls, technical challenges and opportunities of PDT, with a focus on technologies for light activation of photosensitisers, such as light sources, delivery devices, and systems. In this vein, a broad overview of the current status of superficial, interstitial, and deep PDT modalities—and a critical review of light sources and their effects on the PDT process—are presented. Insight into the technical advancements and remaining challenges of optical sources and light devices is provided from a physical and bioengineering perspective.

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“…Many groups have designed and constructed MnO 2 nanoparticle-based nanosystems in order to improve the therapeutic efficacy of PDT 21 - 36 . However, challenges like insufficient and noncontinuous oxygen supply, as well as lack of deep light penetration through living tissues, have not been overcome and therefore limit those developed nanosystems to superficial tumors 27 - 30 , 35 , 37 . The use of near-infrared light (NIR, 700-1100 nm) and NIR-sensitive PSs can maximize penetration in the tissue and achieve efficient treatment in deep tissue tumors.…”

Section: Introductionmentioning

confidence: 99%

Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy

Shen¹,

Xia²,

Ma³

et al. 2020

Theranostics

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Photodynamic therapy (PDT) is a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species (ROS) and eliminate cancer cells under specific wavelength light irradiation. However, special tumor environments, such as those with overexpression of glutathione (GSH), which will consume PDT-mediated ROS, as well as hypoxia in the tumor microenvironment (TME) could lead to ineffective treatment. Moreover, PDT is highly light-dependent and therefore can be hindered in deep tumor cells where light cannot easily penetrate. To solve these problems, we designed oxygen-dual-generating nanosystems MnO 2 @Chitosan-CyI (MCC) for enhanced phototherapy. Methods : The TME-sensitive nanosystems MCC were easily prepared through the self-assembly of iodinated indocyanine green (ICG) derivative CyI and chitosan, after which the MnO 2 nanoparticles were formed as a shell by electrostatic interaction and Mn-N coordinate bonding. Results : When subjected to NIR irradiation, MCC offered enhanced ROS production and heat generation. Furthermore, once endocytosed, MnO 2 could not only decrease the level of GSH but also serve as a highly efficient in situ oxygen generator. Meanwhile, heat generation-induced temperature increase accelerated in vivo blood flow, which effectively relieved the environmental tumor hypoxia. Furthermore, enhanced PDT triggered an acute immune response, leading to NIR-guided, synergistic PDT/photothermal/immunotherapy capable of eliminating tumors and reducing tumor metastasis. Conclusion: The proposed novel nanosystems represent an important advance in altering TME for improved clinical PDT efficacy, as well as their potential as effective theranostic agents in cancer treatment.

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Predictors and Limitations of the Penetration Depth of Photodynamic Effects in the Rodent Brain

Cited by 25 publications

References 81 publications

Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting

Breaking the selectivity-uptake trade-off of photoimmunoconjugates with nanoliposomal irinotecan for synergistic multi-tier cancer targeting

Light Technology for Efficient and Effective Photodynamic Therapy: A Critical Review

Tumor Microenvironment-triggered Nanosystems as dual-relief Tumor Hypoxia Immunomodulators for enhanced Phototherapy

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