Selective Autophagy Pathway of Nanoparticles and Nanodrugs: Drug Delivery and Pathophysiological Effects

Raj, Emmanuel Naveen; Lin, Yu Wei; Chen, Chien Hung; Liu, Kuang Kai; Chao, Jui I.

doi:10.1002/adtp.202000085

Cited by 6 publications

(6 citation statements)

References 271 publications

(442 reference statements)

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“…We reported that ubiquitin decorated NDs bind to autophagy receptors to form nanoparticulosomes for entry into lysosomes and selective autophagy pathway [ 63 ]. The processing of nanoparticles can be through the selective autophagy pathways also called nanoparticulophagy for entering lysosomes [ 64 ]. We suggest that the high specificity of ND-Cet binding to EGFR of lung cancer cells and the EGFR proteins can be transported to lysosome for degradation by the nanoparticulophagy pathway.…”

Section: Discussionmentioning

confidence: 99%

Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody

Lin

Raj

et al. 2022

Pharmaceutics

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Nanoprobes provide advantages for real-time monitoring of tumor markers and tumorigenesis during cancer progression and development. Epidermal growth factor receptor (EGFR) is a key protein that plays crucial roles for tumorigenesis and cancer therapy of lung cancers. Here, we show a carbon-based nanoprobe, nanodiamond (ND), which can be applied for targeting EGFR and monitoring tumorigenesis of human lung cancer cells in vitro and in vivo. The optimal fluorescent intensities of ND particles were observed in the human lung cancer cells and nude mice under in vivo imaging system. The fluorescence signal of ND particles can be real-time detected in the xenografted human lung tumor formation of nude mice. Moreover, the ND-conjugated specific EGFR antibody cetuximab (Cet) can track the location and distribution of EGFR proteins of lung cancer cells in vitro and in vivo. ND-Cet treatment increased cellular uptake ability of nanocomposites in the EGFR-expressed cells but not in the EGFR-negative lung cancer cells. Interestingly, single ND-Cet complex can be directly observed on the protein G bead by immunoprecipitation and confocal microscopy. Besides, the EGFR proteins were transported to lysosomes for degradation. Together, this study demonstrates that ND-conjugated Cet can apply for targeting EGFR and monitoring tumorigenesis during lung cancer progression and therapy.

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Section: Discussionmentioning

confidence: 99%

Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody

Lin

Raj

et al. 2022

Pharmaceutics

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“…Nanoparticles enter cells via endocytosis or other uptake routes. Nanoparticles colocalize with autophagy receptors or markers to produce nanoparticle-containing autophagosomes called nanoparticulosomes [ 70 ]. These ubiquitinated nanoparticles engage with autophagy receptor proteins, SQSTM1 bound to LC3, forming an autophagosome ( Figure 5 ) [ 70 ].…”

Section: Targeting Autophagy Modulation To Eliminate Environmental Su...mentioning

confidence: 99%

“…Nanoparticles colocalize with autophagy receptors or markers to produce nanoparticle-containing autophagosomes called nanoparticulosomes [ 70 ]. These ubiquitinated nanoparticles engage with autophagy receptor proteins, SQSTM1 bound to LC3, forming an autophagosome ( Figure 5 ) [ 70 ]. Nanoparticles affect autophagy by increasing autophagosome production and flux or causing autophagic malfunction [ 71 ].…”

Section: Targeting Autophagy Modulation To Eliminate Environmental Su...mentioning

confidence: 99%

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

Rahman

Parvez

et al. 2023

Toxics

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Autophagy is an evolutionarily conserved cellular system crucial for cellular homeostasis that protects cells from a broad range of internal and extracellular stresses. Autophagy decreases metabolic load and toxicity by removing damaged cellular components. Environmental contaminants, particularly industrial substances, can influence autophagic flux by enhancing it as a protective response, preventing it, or converting its protective function into a pro-cell death mechanism. Environmental toxic materials are also notorious for their tendency to bioaccumulate and induce pathophysiological vulnerability. Many environmental pollutants have been found to influence stress which increases autophagy. Increasing autophagy was recently shown to improve stress resistance and reduce genetic damage. Moreover, suppressing autophagy or depleting its resources either increases or decreases toxicity, depending on the circumstances. The essential process of selective autophagy is utilized by mammalian cells in order to eliminate particulate matter, nanoparticles, toxic metals, and smoke exposure without inflicting damage on cytosolic components. Moreover, cigarette smoke and aging are the chief causes of chronic obstructive pulmonary disease (COPD)-emphysema; however, the disease’s molecular mechanism is poorly known. Therefore, understanding the impacts of environmental exposure via autophagy offers new approaches for risk assessment, protection, and preventative actions which will counter the harmful effects of environmental contaminants on human and animal health.

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“…4−6 Selective autophagy is largely activated by exposure to nanoparticles and nanodrugs, indicating that the selective autophagy pathway may be a subcellular target of nanoparticles or nanodrugs. 3,7,8 Nanoparticulophagy is a selective autophagy pathway for processing nanoparticles and nanodrugs and may be an important mechanism in regulating drug delivery and biological effects. Selective autophagy relies on the recognition and degradation of various autophagic substrates or cargos.…”

Section: Introductionmentioning

confidence: 99%

“…The increasing application of nanodrugs in cancer therapy and diagnosis has raised concerns about their pathophysiological effects. − Selective autophagy is a highly conserved process for the sequestration and transport of macromolecules and organelles to the lysosome for degradation. − Selective autophagy is largely activated by exposure to nanoparticles and nanodrugs, indicating that the selective autophagy pathway may be a subcellular target of nanoparticles or nanodrugs. ,, Nanoparticulophagy is a selective autophagy pathway for processing nanoparticles and nanodrugs and may be an important mechanism in regulating drug delivery and biological effects. , …”

Section: Introductionmentioning

confidence: 99%

Enhancing Efficacy of Albumin-Bound Paclitaxel for Human Lung and Colorectal Cancers through Autophagy Receptor Sequestosome 1 (SQSTM1)/p62-Mediated Nanodrug Delivery and Cancer therapy

Lin,

Chen

et al. 2023

ACS Nano

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Selective autophagy is a defense mechanism by which foreign pathogens and abnormal substances are processed to maintain cellular homeostasis. Sequestosome 1 (SQSTM1)/p62, a vital selective autophagy receptor, recruits ubiquitinated cargo to form autophagosomes for lysosomal degradation. Nab-PTX is an albumin-bound paclitaxel nanoparticle used in clinical cancer therapy. However, the role of SQSTM1 in regulating the delivery and efficacy of nanodrugs remains unclear. Here we showed that SQSTM1 plays a crucial role in Nab-PTX drug delivery and efficacy in human lung and colorectal cancers. Nab-PTX induces SQSTM1 phosphorylation at Ser403, which facilitates its incorporation into the selective autophagy of nanoparticles, known as nanoparticulophagy. Nab-PTX increased LC3-II protein expression, which triggered autophagosome formation. SQSTM1 enhanced Nab-PTX recognition to form autophagosomes, which were delivered to lysosomes for albumin degradation, thereby releasing PTX to induce mitotic catastrophe and apoptosis. Knockout of SQSTM1 downregulated Nab-PTX-induced mitotic catastrophe, apoptosis, and tumor inhibition in vitro and in vivo and inhibited Nab-PTX-induced caspase 3 activation via a p53-independent pathway. Ectopic expression of SQSTM1 by transfection of an SQSTM1-GFP vector restored the drug efficacy of Nab-PTX. Importantly, SQSTM1 is highly expressed in advanced lung and colorectal tumors and is associated with poor overall survival in clinical patients. Targeting SQSTM1 may provide an important strategy to improve nanodrug efficacy in clinical cancer therapy. This study demonstrates the enhanced efficacy of Nab-PTX for human lung and colorectal cancers via SQSTM1-mediated nanodrug delivery.

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Selective Autophagy Pathway of Nanoparticles and Nanodrugs: Drug Delivery and Pathophysiological Effects

Cited by 6 publications

References 271 publications

Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody

Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

Enhancing Efficacy of Albumin-Bound Paclitaxel for Human Lung and Colorectal Cancers through Autophagy Receptor Sequestosome 1 (SQSTM1)/p62-Mediated Nanodrug Delivery and Cancer therapy

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