Upconversion superballs for programmable photoactivation of therapeutics

Zhang, Zhen; Jayakumar, Muthu Kumara Gnanasammandhan; Zheng, Xiang; Shikha, Swati; Zhang, Yi; Bansal, Akshaya; Poon, Dennis; Chu, Pek Lim; Yeo, Eugenia Li Ling; Chua, Melvin L.K.; Chee, Soo Khee; Zhang, Yong

doi:10.1038/s41467-019-12506-w

Cited by 113 publications

(127 citation statements)

References 37 publications

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“…Likewise, UV light is widely reported as a phototoxic agent that can be potentially carcinogenic [ 317 ]. In contrast, near-infrared (NIR) light exhibits higher tissue penetration compared to UV or visible light [ 313 ] but much lower absorption rates in biological tissues [ 313 , 318 ]. As a result, this technology offers reduced phototoxic effect, which makes it a promising alternative for the implementation of PCI at clinical and experimental levels [ 317 , 318 , 319 ].…”

Section: Enhancing Ion Endosomal Escapementioning

confidence: 99%

“…In contrast, near-infrared (NIR) light exhibits higher tissue penetration compared to UV or visible light [ 313 ] but much lower absorption rates in biological tissues [ 313 , 318 ]. As a result, this technology offers reduced phototoxic effect, which makes it a promising alternative for the implementation of PCI at clinical and experimental levels [ 317 , 318 , 319 ]. In fact, a recent report has demonstrated the biomedical application of NIR PCI through either direct irradiation or via local conversion with the aid of nanoparticles [ 320 ].…”

Section: Enhancing Ion Endosomal Escapementioning

confidence: 99%

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Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

et al. 2020

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Iron oxide nanoparticles (IONs) have been widely explored for biomedical applications due to their high biocompatibility, surface-coating versatility, and superparamagnetic properties. Upon exposure to an external magnetic field, IONs can be precisely directed to a region of interest and serve as exceptional delivery vehicles and cellular markers. However, the design of nanocarriers that achieve an efficient endocytic uptake, escape lysosomal degradation, and perform precise intracellular functions is still a challenge for their application in translational medicine. This review highlights several aspects that mediate the activation of the endosomal pathways, as well as the different properties that govern endosomal escape and nuclear transfection of magnetic IONs. In particular, we review a variety of ION surface modification alternatives that have emerged for facilitating their endocytic uptake and their timely escape from endosomes, with special emphasis on how these can be manipulated for the rational design of cell-penetrating vehicles. Moreover, additional modifications for enhancing nuclear transfection are also included in the design of therapeutic vehicles that must overcome this barrier. Understanding these mechanisms opens new perspectives in the strategic development of vehicles for cell tracking, cell imaging and the targeted intracellular delivery of drugs and gene therapy sequences and vectors.

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Section: Enhancing Ion Endosomal Escapementioning

confidence: 99%

Section: Enhancing Ion Endosomal Escapementioning

confidence: 99%

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

et al. 2020

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“…Zhang et al [173] developed upconversion core-shell NPs which they named orthogonal photoactivatable superballs (OP-SBs). The OP-SBs were based on two different upconversion NP moieties mixed in different ratios: one resulting in high absorption at 980 nm (high tissue penetration) and strong red-light emission and another one, absorbing at 808 nm and emitting in the blue and UV.…”

Section: Pci Mediated Oligonucleotide Deliverymentioning

confidence: 99%

Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research

Jerjes¹,

Theodossiou

Hirschberg

et al. 2020

JCM

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Photochemical internalisation (PCI) is a unique intervention which involves the release of endocytosed macromolecules into the cytoplasmic matrix. PCI is based on the use of photosensitizers placed in endocytic vesicles that, following light activation, lead to rupture of the endocytic vesicles and the release of the macromolecules into the cytoplasmic matrix. This technology has been shown to improve the biological activity of a number of macromolecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus and oligonucleotides and certain chemotherapeutics, such as bleomycin. This new intervention has also been found appealing for intracellular delivery of drugs incorporated into nanocarriers and for cancer vaccination. PCI is currently being evaluated in clinical trials. Data from the first-in-human phase I clinical trial as well as an update on the development of the PCI technology towards clinical practice is presented here.

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“…The wide range of emission spectrum that can be engineered into UCNPs makes such implants multiplexable for activating multipledrugs at once, without cross-interference. [26] Furthermore, UCNPs implantable technology is also expandable to other phototherapeutics, including wireless optogenetic study and photo-biomodulations. [27,28] Figure 3.…”

Section: Doi: 101002/adma202001459mentioning

confidence: 99%

A Flexi‐PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy

et al. 2020

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Near‐infrared (NIR) activatable upconversion nanoparticles (UCNPs) enable wireless‐based phototherapies by converting deep‐tissue‐penetrating NIR to visible light. UCNPs are therefore ideal as wireless transducers for photodynamic therapy (PDT) of deep‐sited tumors. However, the retention of unsequestered UCNPs in tissue with minimal options for removal limits their clinical translation. To address this shortcoming, biocompatible UCNPs implants are developed to deliver upconversion photonic properties in a flexible, optical guide design. To enhance its translatability, the UCNPs implant is constructed with an FDA‐approved poly(ethylene glycol) diacrylate (PEGDA) core clad with fluorinated ethylene propylene (FEP). The emission spectrum of the UCNPs implant can be tuned to overlap with the absorption spectra of the clinically relevant photosensitizer, 5‐aminolevulinic acid (5‐ALA). The UCNPs implant can wirelessly transmit upconverted visible light till 8 cm in length and in a bendable manner even when implanted underneath the skin or scalp. With this system, it is demonstrated that NIR‐based chronic PDT is achievable in an untethered and noninvasive manner in a mouse xenograft glioblastoma multiforme (GBM) model. It is postulated that such encapsulated UCNPs implants represent a translational shift for wireless deep‐tissue phototherapy by enabling sequestration of UCNPs without compromising wireless deep‐tissue light delivery.

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Upconversion superballs for programmable photoactivation of therapeutics

Cited by 113 publications

References 37 publications

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

Tailoring Iron Oxide Nanoparticles for Efficient Cellular Internalization and Endosomal Escape

Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research

A Flexi‐PEGDA Upconversion Implant for Wireless Brain Photodynamic Therapy

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