Toward Precise Antitumoral Photodynamic Therapy Using a Dual Receptor‐Mediated Bioorthogonal Activation Approach

Chu, Jacky; Wong, Chi‐Ming; Ng, Dennis K. P.

doi:10.1002/ange.202214473

Cited by 3 publications

(3 citation statements)

References 68 publications

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“…Thus far, carrier-free delivery of cytochrome C remains rare, and nonspecific delivery is often encountered [ 42 ]. Recently, our group has developed several carrier-free strategies for selectively delivering bioactive proteins such as green fluorescent protein and ß-galactosidase, as well as small molecules, into tumour cells by conjugating them with tumour-specific binding peptides against tumour biomarkers such as integrin and EGFR [ 43 , 44 , 45 , 46 , 47 ]. These cargos can specifically target these surface biomarkers and enter intracellular space through receptor-mediated endocytosis.…”

Section: Discussionmentioning

confidence: 99%

Chemical Modification of Cytochrome C for Acid-Responsive Intracellular Apoptotic Protein Delivery for Cancer Eradication

Tang,

Lau,

Zhu

et al. 2024

Pharmaceutics

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Delivering bioactive proteins into cells without carriers presents significant challenges in biomedical applications due to limited cell membrane permeability and the need for targeted delivery. Here, we introduce a novel carrier-free method that addresses these challenges by chemically modifying proteins with an acid-responsive cell-penetrating peptide (CPP) for selective intracellular delivery within tumours. Cytochrome C, a protein known for inducing apoptosis, served as a model for intracellular delivery of therapeutic proteins for cancer treatment. The CPP was protected with 2,3-dimethyl maleic anhydride (DMA) and chemically conjugated onto the protein surface, creating an acid-responsive protein delivery system. In the acidic tumour microenvironment, DMA deprotects and exposes the positively charged CPP, enabling membrane penetration. Both in vitro and in vivo assays validated the pH-dependent shielding mechanism, demonstrating the modified cytochrome C could induce apoptosis in cancer cells in a pH-selective manner. These findings provide a promising new approach for carrier-free and tumour-targeted intracellular delivery of therapeutic proteins for a wide range of potential applications.

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Section: Discussionmentioning

confidence: 99%

Chemical Modification of Cytochrome C for Acid-Responsive Intracellular Apoptotic Protein Delivery for Cancer Eradication

Tang,

Lau,

Zhu

et al. 2024

Pharmaceutics

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“…This system consists of two components, a biotin-modified tetrazine-substituted PS and a cyclic EGFR-targeting peptide linked with a bicycle[6.1.0]non-4-yne dienophile, which are preferentially internalized only by cancer cells expressing both biotin receptors and EGFR, followed by a rapid bio-orthogonal inverse electron-demand Diels-Alder reaction to form the corresponding cycloadduct, thereby restoring the PS's ability to fluoresce and generate ROS. 208 Due to the good in vitro targeting behavior of actively targeted nanomedicines, their related studies are increasing year by year. However, in vivo, the complex TME often affects the targeting effect of actively targeted nanoparticles.…”

Section: Active Targeting Of Pss To Tumorsmentioning

confidence: 99%

“…Ng's group has devised a novel strategy for activating such a PS specifically in the target cells via dual receptor‐mediated bioorthogonal coupling. This system consists of two components, a biotin‐modified tetrazine‐substituted PS and a cyclic EGFR‐targeting peptide linked with a bicycle[6.1.0]non‐4‐yne dienophile, which are preferentially internalized only by cancer cells expressing both biotin receptors and EGFR, followed by a rapid bio‐orthogonal inverse electron‐demand Diels‐Alder reaction to form the corresponding cycloadduct, thereby restoring the PS's ability to fluoresce and generate ROS 208 …”

Section: Nanocarriers For Pdt Applicationmentioning

confidence: 99%

Photodynamic therapy for cancer: mechanisms, photosensitizers, nanocarriers, and clinical studies

Zhao,

Wang,

Zhang

et al. 2024

MedComm

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Photodynamic therapy (PDT) is a temporally and spatially precisely controllable, noninvasive, and potentially highly efficient method of phototherapy. The three components of PDT primarily include photosensitizers, oxygen, and light. PDT employs specific wavelengths of light to active photosensitizers at the tumor site, generating reactive oxygen species that are fatal to tumor cells. Nevertheless, traditional photosensitizers have disadvantages such as poor water solubility, severe oxygen‐dependency, and low targetability, and the light is difficult to penetrate the deep tumor tissue, which remains the toughest task in the application of PDT in the clinic. Here, we systematically summarize the development and the molecular mechanisms of photosensitizers, and the challenges of PDT in tumor management, highlighting the advantages of nanocarriers‐based PDT against cancer. The development of third generation photosensitizers has opened up new horizons in PDT, and the cooperation between nanocarriers and PDT has attained satisfactory achievements. Finally, the clinical studies of PDT are discussed. Overall, we present an overview and our perspective of PDT in the field of tumor management, and we believe this work will provide a new insight into tumor‐based PDT.

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β‐Galactosidase‐Triggered Photodynamic Elimination of Senescent Cells with a Boron Dipyrromethene‐Based Photosensitizer

Chu,

Escriche‐Navarro,

Xiong

et al. 2024

Advanced Science

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Senescence is a cellular response having physiological and reparative functions to preserve tissue homeostasis and suppress tumor growth. However, the accumulation of senescent cells would cause deleterious effects that lead to age‐related dysfunctions and cancer progression. Hence, selective detection and elimination of senescent cells are crucial yet remain a challenge. A β‐galactosidase (β‐gal)‐activated boron dipyrromethene (BODIPY)‐based photosensitizer (compound 1) is reported here that can selectively detect and eradicate senescent cells. It contains a galactose moiety connected to a pyridinium BODIPY via a self‐immolative nitrophenylene linker, of which the photoactivity is effectively quenched. Upon interactions with the senescence‐associated β‐gal, it undergoes enzymatic hydrolysis followed by self‐immolation, leading to the release of an activated BODIPY moiety by which the fluorescence emission and singlet oxygen generation are restored. The ability of 1 to detect and eliminate senescent cells is demonstrated in vitro and in vivo, using SK‐Mel‐103 tumor‐bearing mice treated with senescence‐inducing therapy. The results demonstrate that 1 can be selectively activated in senescent cells to trigger a robust senolytic effect upon irradiation. This study breaks new ground in the design and application of new senolytic agents based on photodynamic therapy.

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Toward Precise Antitumoral Photodynamic Therapy Using a Dual Receptor‐Mediated Bioorthogonal Activation Approach

Cited by 3 publications

References 68 publications

Chemical Modification of Cytochrome C for Acid-Responsive Intracellular Apoptotic Protein Delivery for Cancer Eradication

Chemical Modification of Cytochrome C for Acid-Responsive Intracellular Apoptotic Protein Delivery for Cancer Eradication

Photodynamic therapy for cancer: mechanisms, photosensitizers, nanocarriers, and clinical studies

β‐Galactosidase‐Triggered Photodynamic Elimination of Senescent Cells with a Boron Dipyrromethene‐Based Photosensitizer

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