MMP9‐Responsive Graphene Oxide Quantum Dot‐Based Nano‐in‐Micro Drug Delivery System for Combinatorial Therapy of Choroidal Neovascularization

Huang, Kangdi; Liu, Xin; Lv, Ziru; Zhang, Di; Zhou, Yanmin; Lin, Zhiqing; Guo, Juan

doi:10.1002/smll.202207335

Cited by 15 publications

(13 citation statements)

References 84 publications

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“…PANC-1 cells were treated with si-ZDHHC3 or si-Control for 48 h. Then, cells were harvested, and total RNA was extracted. The subsequent procedures were consistent with those in our previous study [ 37 ]. PD-L1 forward primer (5′-GCTATGGTGGTGCCGACTAC-3′), PD-L1 reverse primer (5′-TGGCTCCCAGAATTACCAAGT-3′); GAPDH forward primer (5′-CGCTCTCTGCTCCTCCTGTTC-3′) GAPDH reverse primer (5′-ATCCGTTGACTCCGACCTTCAC-3′).…”

Section: Methodssupporting

confidence: 79%

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RETRACTED ARTICLE: Palmitoyl transferases act as novel drug targets for pancreatic cancer

Lin

Liu

et al. 2023

J Transl Med

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Background Pancreatic adenocarcinoma (PAAD) is one of the most leading causes of cancer-related death across the world with the limited efficiency and response rate of immunotherapy. Protein S-palmitoylation, a powerful post-translational lipid modification, is well-known to regulate the stability and cellular distribution of cancer-related proteins, which is mediated by a family of 23 palmitoyl transferases, namely zinc finger Asp-His-His-Cys-type (ZDHHC). However, whether palmitoyl transferases can determine tumor progression and the efficacy of immunotherapy in PAAD remains unknown. Methods Bioinformatics methods were used to identify differential ZDHHCs expression in PAAD. A systematic pan-cancer analysis was conducted to assess the immunological role of ZDHHC3 using RNA sequencing data from The Cancer Genome Atlas database. In vivo Panc 02 subcutaneous tumor model validated the anti-tumor effect of knockdown of ZDHHC3 or intraperitoneal injection of 2-bromopalmitate (2-BP), a typical broad-spectrum palmitoyl transferases inhibitor. Furthermore, we explored therapeutic strategies with combinations of 2-BP with PD-1/PD-L1-targeted immunotherapy in C57BL/6 mice bearing syngeneic Panc 02 pancreatic tumors. Results ZDHHC enzymes were associated with distinct prognostic values of pancreatic cancer. We identified that ZDHHC3 expression promotes an immunosuppressive tumor microenvironment in PAAD. 2-BP suppressed pancreatic-tumor cell viability and tumor sphere-forming activities, as well as increased cell apoptosis in vitro, without affecting normal human pancreatic ductal epithelial cells. Furthermore, genetic inactivation of ZDHHC3 or intraperitoneal injection of 2-BP impeded tumor progression in Panc 02 pancreatic tumors with enhanced anti-tumor immunity. 2-BP treatment significantly enhanced the therapeutic efficacy of PD-1/PD-L1 inhibitors in Panc 02 pancreatic tumors. Conclusion This study revealed some ZDHHC enzyme genes for predicting the prognosis of pancreatic cancer, and demonstrated that ZDHHC3 plays a critical oncogenic role in pancreatic cancer progression, highlighting its potential as an immunotherapeutic target of pancreatic cancer. In addition, combination therapy of 2-BP and PD-1/PD-L1 achieved synergic therapy effects in a mouse model of pancreatic cancer.

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Section: Methodssupporting

confidence: 79%

“…Assessment of cell apoptosis was performed using the cell apoptosis detection kit (Annexin V-FITC/PI, Dojindo) as previously described [ 37 ]. Briefly, Panc 02, PANC-1, and HPDE6-C7 cells were seeded into 24-well plates with 500 µL of culture medium at an initial density of 50,000 cells per well.…”

Section: Methodsmentioning

confidence: 99%

RETRACTED ARTICLE: Palmitoyl transferases act as novel drug targets for pancreatic cancer

Lin

Liu

et al. 2023

J Transl Med

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“…The key factor is the presence of GOQD, which has antioxidant characteristics [ 73 ], and HMW hyaluronic acid, which has anti-inflammatory properties. In addition, because GOQDs are graphene based materials and have more side groups than GQDs, they can be easily functionalized with other macromolecules [ 81 ]. While the same planar graphene structure and side groups that include OH and COOH groups make it a better option for drug loading [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

Hyaluronic acid-graphene oxide quantum dots nanoconjugate as dual purpose drug delivery and therapeutic agent in meta-inflammation

et al. 2023

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Type 2 diabetes mellitus (T2DM) predominantly considered a metabolic disease is now being considered an inflammatory disease as well due to the involvement of meta-inflammation. Obesity-induced adipose tissue inflammation (ATI) is one of the earliest phenomena in the case of meta-inflammation, leading to the advent of insulin resistance (IR) and T2DM. The key events of ATI are orchestrated by macrophages, which aggravate the inflammatory state in the tissue upon activation, ultimately leading to systemic chronic low-grade inflammation and Non-Alcoholic Steatohepatitis (NASH) through the involvement of proinflammatory cytokines. The CD44 receptor on macrophages is overexpressed in ATI, NASH, and IR. Therefore, we developed a CD44 targeted Hyaluronic Acid functionalized Graphene Oxide Quantum Dots (GOQD-HA) nanocomposite for tissue-specific delivery of metformin. Metformin-loaded GOQD-HA (GOQD-HA-Met) successfully downregulated the expression of proinflammatory cytokines and restored antioxidant status at lower doses than free metformin in both palmitic acid-induced RAW264.7 cells and diet induced obese mice. Our study revealed that the GOQD-HA nanocarrier enhanced the efficacy of Metformin primarily by acting as a therapeutic agent apart from being a drug delivery platform. The therapeutic properties of GOQD-HA stem from both HA and GOQD having anti-inflammatory and antioxidant properties respectively. This study unravels the function of GOQD-HA as a targeted drug delivery option for metformin in meta-inflammation where the nanocarrier itself acts as a therapeutic agent. Graphical Abstract

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“…Using a laser-induced CNV mouse model, the prepared C18PGM shows significant MMP9 inhibitory activity and anti-inflammatory action followed by antiangiogenic effects. [ 82 ] ChR@Ag-rGONCs and ChR@Au-rGONCs MDA-MD-468 and MDA-MD-231 The presence of noble metal NPs on the rGO surface improved its thermal stability and performances in diverse physiological conditions. Moreover, the surface passivation of the fabricated NCs with natural anticancer flavone ChR improved its biocompatibility.…”

Section: Summary and Future Perspectivementioning

confidence: 99%

Chasing Graphene-Based Anticancer Drugs: Where are We Now on the Biomedical Graphene Roadmap?

Uzdrowska,

Knap,

Gulczynski

et al. 2024

IJN

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Graphene and graphene-based materials have attracted growing interest for potential applications in medicine because of their good biocompatibility, cargo capability and possible surface functionalizations. In parallel, prototypic graphene-based devices have been developed to diagnose, imaging and track tumor growth in cancer patients. There is a growing number of reports on the use of graphene and its functionalized derivatives in the design of innovative drugs delivery systems, photothermal and photodynamic cancer therapy, and as a platform to combine multiple therapies. The aim of this review is to introduce the latest scientific achievements in the field of innovative composite graphene materials as potentially applied in cancer therapy. The “Technology and Innovation Roadmap” published in the Graphene Flagship indicates, that the first anti-cancer drugs using graphene and graphene-derived materials will have appeared on the market by 2030. However, it is necessary to broaden understanding of graphene-based material interactions with cellular metabolism and signaling at the functional level, as well as toxicity. The main aspects of further research should elucidate how treatment methods (e.g., photothermal therapy, photodynamic therapy, combination therapy) and the physicochemical properties of graphene materials influence their ability to modulate autophagy and kill cancer cells. Interestingly, recent scientific reports also prove that graphene nanocomposites modulate cancer cell death by inducing precise autophagy dysfunctions caused by lysosome damage. It turns out as well that developing photothermal oncological treatments, it should be taken into account that near-infrared-II radiation (1000–1500 nm) is a better option than NIR-I (750–1000 nm) because it can penetrate deeper into tissues due to less scattering at longer wavelengths radiation.

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MMP9‐Responsive Graphene Oxide Quantum Dot‐Based Nano‐in‐Micro Drug Delivery System for Combinatorial Therapy of Choroidal Neovascularization

Cited by 15 publications

References 84 publications

RETRACTED ARTICLE: Palmitoyl transferases act as novel drug targets for pancreatic cancer

RETRACTED ARTICLE: Palmitoyl transferases act as novel drug targets for pancreatic cancer

Hyaluronic acid-graphene oxide quantum dots nanoconjugate as dual purpose drug delivery and therapeutic agent in meta-inflammation

Chasing Graphene-Based Anticancer Drugs: Where are We Now on the Biomedical Graphene Roadmap?

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