Tumor microenvironment-responsive multifunctional peptide coated ultrasmall gold nanoparticles and their application in cancer radiotherapy

Ding, Yuan; Sun, Zhongquan; Tong, Zongrui; Zhang, Sitong; Min, Jie; Xu, Qianhui; Zhou, Liuzhi; Mao, Zhengwei; Xia, Haibing; Wang, Weilin

doi:10.7150/thno.45017

Cited by 85 publications

(54 citation statements)

References 56 publications

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“…Among them, an increasing number of gold nanoparticles (AuNP)-conjugated peptide have been developed and applied for clinical trials in because of its intrinsic advantage including essential inertion, low-toxicity and economic costs 22 - 25 . Up to now, AuNPs have provided non-toxic carriers for drugs and biomolecules delivery applications 26 - 28 . Yet the complex chemical properties (hydrophobicity, charge and redox) of peptide are always adverse to the steady state of colloidal AuNP after conjugation, resulting in the subsequent aggregation or even precipitation under the physiological condition of the elevated ionic concentration 29 , 30 .…”

Section: Introductionmentioning

confidence: 99%

A general-purpose Nanohybrid fabricated by Polymeric Au(I)-peptide precursor to wake the function of Peptide Therapeutics

Yan¹,

Ji²,

Yan³

et al. 2020

Theranostics

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Peptide-derived nanocomposites have been exhibiting fascinating biological advantages, including but not limited to excellent biocompatibility, biological degradation, high targetability and subsequent potent therapeutic efficacy. While some successes have been achieved in the nanoengineering of peptide-based architectures with defined dimensions and medical functions, enormous challenges remain about clinical nano-pharmaceutics of peptides, especially those modulating intracellular protein-protein interactions (PPIs). Methods: We developed a general method to translate intracellular-PPI-targeted peptides into a bioavailable peptide-auric s pheroidal n ano h ybrid (SNH), for which polymeric peptide-Auric precursors [Au 1+ -S-peptide] n are in-situ reduced on the surface of gold nanoseeds via a simple and mild reaction. As proofs of concept, three cytomembrane-impenetrable peptides with different physicochemical properties were successfully engineered into stable and tumor-specific SNH respectively. Results: To highlight the advantage of SNH, PMI, a hydrophobic and enzyme-intolerant peptide capable of p53 restoration, was selected to challenge the power of SNH in a colon tumor xenografts model. PMI-Au SNH in vivo suppressed tumor growth potently after three administrations: intravenous injection, intraperitoneal injection and gastric perfusion, and maintained a favorable therapeutic safety. Conclusion: This therapeutically feasible strategy of peptide nanoengineering will allow us to fabricate a series of nanomedicines to modulate carcinogenic PPIs that hide and multiply inside cells, and in all likelihood reinvigorate the development of peptide drug against wide varieties of human diseases.

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Section: Introductionmentioning

confidence: 99%

A general-purpose Nanohybrid fabricated by Polymeric Au(I)-peptide precursor to wake the function of Peptide Therapeutics

Yan¹,

Ji²,

Yan³

et al. 2020

Theranostics

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“…Excessive ROS in cells can destroy proteins, DNA, phospholipids, and other biological macromolecules. The generation of ROS is one main anticancer mechanism of radiotherapy and several therapeutic agents [ 1 , 37 – 39 ]. Therefore, it is of great clinical and theoretical significance to measure the effect of NPs on intracellular ROS production.…”

Section: Resultsmentioning

confidence: 99%

“…Importantly, DCFH cannot penetrate the cell membrane, so the DCFH-DA probe remains inside the cell. Intracellular ROS oxidizes the nonfluorescent DCFH to produce fluorescent DCF [ 1 , 31 ]. Thus, the intracellular ROS level can be measured by detecting the fluorescence of intracellular DCF.…”

Section: Resultsmentioning

confidence: 99%

“…In the natural biological setting, ROS is a by-product of oxygen metabolism and plays an important role in cell signaling and homeostasis [ 51 , 52 ]. However, ROS levels can dramatically increase during environmental pressures (e.g., after UV or heat exposure), potentially causing oxidative stress or serious damage to cell structures [ 1 , 31 ]. Thus, we can measure possible cytotoxicity by determining the effect of SNS on ROS production and metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Nanoparticle (NP) systems have arisen as a popular strategy among researchers seeking to improve methods of diagnosis and treatment for a wide range of diseases and have resulted in a number of approved diagnose/therapies such as Ferumoxytol, albumin-bound paclitaxel, and Onivyde [ 1 – 6 ]. Nanosystems are primarily used as drug loading or delivery carriers (e.g., for small molecules, proteins/peptides, or gene therapies) or directly as imaging agents [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Preparation, Biosafety, and Cytotoxicity Studies of a Newly Tumor-Microenvironment-Responsive Biodegradable Mesoporous Silica Nanosystem Based on Multimodal and Synergistic Treatment

Zhang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Patients with triple negative breast cancer (TNBC) often suffer relapse, and clinical improvements offered by radiotherapy and chemotherapy are modest. Although targeted therapy and immunotherapy have been a topic of significant research in recent years, scientific developments have not yet translated to significant improvements for patients with TNBC. In view of these current clinical treatment shortcomings, we designed a silica nanosystem (SNS) with Nano-Ag as the core and a complex of MnO2 and doxorubicin (Dox) as the surrounding mesoporous silica shell. This system was coated with anti-PD-L1 to target the PD-L1 receptor, which is highly expressed on the surface of tumor cells. MnO2 itself has been shown to act as chemodynamic therapy (CDT), and Dox is cytotoxic. Thus, the full SNS system presents a multimodal, potentially synergistic strategy for the treatment of TNBC. Given potential interest in the clinical translation of SNS, the biological safety and antitumor activity of SNS were evaluated in a series of studies that included physicochemical characterization, particle stability, blood compatibility, and cytotoxicity. We found that the particle size and zeta potential of SNS were 94.6 nm and -22.1 mV, respectively. Ultraviolet spectrum analysis showed that Nano-Ag, Dox, and MnO2 were successfully loaded into SNS, and the drug loading ratio of Dox was about 10.2%. Stability studies found that the particle size of SNS did not change in different solutions. Hemolysis tests showed that SNS, at levels far exceeding the anticipated physiologic concentrations, did not induce red blood cell lysis. Further in vitro and in vivo experiments found that SNS did not activate platelets or cause coagulopathy and had no significant effects on the total number of blood cells or hepatorenal function. Cytotoxicity experiments suggested that SNS significantly inhibited the growth of tumor cells by damaging cell membranes, increasing intracellular ROS levels, inhibiting the release of TGF-β1 cytokines by macrophages, and inhibiting intracellular protein synthesis. In general, SNS appeared to have favorable biosafety and antitumor effects and may represent an attractive new therapeutic approach for the treatment of TNBC.

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Metallodrugs: an approach against invasion and metastasis in cancer treatment

2022

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Cancer is a heterogeneous and multifactorial disease that causes high mortality throughout the world; therefore, finding the most effective therapies is a major research challenge. Currently, most anticancer drugs present a limited number of well‐established targets, such as cell proliferation or death; however, it is important to consider that the worse progression of cancer toward pathological stages implies invasion and metastasis processes. Medicinal Inorganic Chemistry (MIC) is a young area that deals with the design, synthesis, characterization, preclinical evaluation, and mechanism of action of new inorganic compounds, called metallodrugs. The properties of metallic ions allow enriching of strategies for the design of new drugs, enabling the adjustment of physicochemical and stereochemical properties. Metallodrugs can adopt geometries, such as tetrahedral, octahedral, square planar, and square planar pyramid, which adjusts their arrangement and facilitates binding with a wide variety of targets. The redox properties of some metal ions can be modulated by the presence of the bound ligands to adjust their interaction, thereby opening a range of mechanisms of action. In this regard, the mechanisms of action that trigger the biological activity of metallodrugs have been generally identified by: (a) coordination of the metal to biomolecules (for instance, cisplatin binds to the N7 in DNA guanine, as Pt‐N via coordination of the inhibition of enzymes); (b) redox‐active; and (c) ROS production. For this reason, a series of metallodrugs can interact with several specific targets in the anti‐invasive processes of cancer and can prevent metastasis. The structural base of several metal compounds shows great anticancer potential by inhibiting the signaling pathways related to cancer progression. In this minireview, we present the advances in the field of antimetastatic effects of metallodrugs.

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Tumor microenvironment-responsive multifunctional peptide coated ultrasmall gold nanoparticles and their application in cancer radiotherapy

Cited by 85 publications

References 56 publications

A general-purpose Nanohybrid fabricated by Polymeric Au(I)-peptide precursor to wake the function of Peptide Therapeutics

A general-purpose Nanohybrid fabricated by Polymeric Au(I)-peptide precursor to wake the function of Peptide Therapeutics

Preparation, Biosafety, and Cytotoxicity Studies of a Newly Tumor-Microenvironment-Responsive Biodegradable Mesoporous Silica Nanosystem Based on Multimodal and Synergistic Treatment

Metallodrugs: an approach against invasion and metastasis in cancer treatment

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